111 research outputs found

    Constitutions in a World of Powerful Semi-Autonomous Social Fields

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    Risk Decisions in German Constitutional and Administrative Law

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    The alternative law of alternative dispute resolution

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    The perceptions afforded by the study of legal pluralism assist an understanding of the full scope and the social and moral significance of alternative dispute resolution. The latter term includes all modes and forms of dispute resolution within the legal order of the state other than the usual forms of adjudication by the ordinary courts. These modes may be classified in relatively wide and fluid categories as other forms of adjudication, and arbitration, mediation and negotiation. However, alternative dispute resolution also includes instances of all these processes which are not established, adopted, or made effective by the state. The study of legal pluralism throughout the world shows that almost everywhere are many such instances, generated within many semi-autonomous social fields other than the state, and falling into all the listed categories. The study of legal pluralism further suggests that the different dispute settlement processes are likely to be associated with different bodies of legal norms. There is evidence that to some extent alternative state processes employ different bodies of laws. The evidence also shows that non-state processes employ bodies of norms which always differ, and may differ widely from those of state law. While legal centralism denies these norms the name of "laws", there seems no good reason not to classify such rules and principles, which order relations within social fields other than the state, as "customary law", or by some similar term. Alternative dispure resolution processes have been lauded as enhancing the effectiveness of the law, providing wider access to justice or law. However, if the argument presented here is correct, it is not sufficient to represent them as implementing "the law". Rather each implements a different variety of law. The social functions of these different laws of different dispute resolution processes, both state and non-state, vary, and so need investigation in each particular case. Whether any law is to be approved as affecting power relations in the society concerned is similarly a matter for investigation. While it has been suggested that alternative dispute resolution processes can confer on the weak and underprivileged an opportunity to assert their interests, it has been argued against such a view that they may provide opportunities for the already powerful to increase their powers, free of the restraining influence of regular state courts. On the other hand, state processes may at certain historical moments be manipulated by the weak to their advantage. Non-state processes may, also in special circumstances, empower collectively the members of the social fields in which they operate.La vision pluraliste du droit aide √† bien comprendre la port√©e et la signification sociale et morale des modes alternatifs de solution des conflits, c'est-√†-dire, par rapport √† l‚Äôordre juridique √©tatique, des modes de solution autres que celui correspondant √† l'intervention d√©cisionnelle des tribunaux ordinaires. Ces modes peuvent se rattacher √† une typologie souple qui inclut d'autres formes d'adjudication, l'arbitrage, la m√©diation et la n√©gociation. Mais, on doit tout aussi bien comprendre d'autres voies √©tablies et pratiqu√©es sans le concours de l'√Čtat. L'√©tude du pluralisme juridique en tant que ph√©nom√®ne universel permet de constater l'existence quasi universelle de tels forums correspondant √† plusieurs ordres sociaux semi-autonomes et non √©tatiques. L'√©tude du pluralisme juridique incite de plus √† poser que les diff√©rents modes de solutions des conflits ont tendance √† √™tre associ√©s √† diff√©rents corpus de normes juridiques. On peut d√©montrer, pour ce qui est de l'ordre √©tatique, que, dans une certaine mesure, les modes alternatifs font appel √† diff√©rents ensembles normatifs. Quant aux voies non √©tatiques, on peut √©galement √©tablir que les normes appliqu√©es diff√®rent, parfois m√™me de fa√ßon marqu√©e, du droit √©tatique. Bien qu'une conception centralis√©e du droit refuse de qualifier de¬†‚Äújurisprudence‚ÄĚ ces normes, aucune v√©ritable raison ne permet de refuser de tenir ces r√®gles et principes, qui r√©gissent des ordres sociaux autre que l'√Čtat, pour du ‚Äúdroit coutumier‚ÄĚ, au sens g√©n√©ral du terme. On a souvent reconnu aux modes alternatifs de solution des conflits l'avantage de promouvoir l‚Äôeffectivit√© du droit, d'√©largir l'acc√®s √† la justice ou au droit. Cependant, si la pr√©sente th√®se est correcte, il ne suffit plus de s'en tenir √† cet apport reli√© √† l'application du droit. En fait, chacun des modes alternatifs met en oeuvre une esp√®ce distincte de droit. Les fonctions sociales de ces diff√©rents droits correspondant √† diff√©rents modes de solution de conflits, qu'ils soient ou non √©tatiques, varient; d'o√Ļ la n√©cessit√© d'une approche sp√©cifique. De m√™me, doit-on √©tudier, dans toute soci√©t√© donn√©e, si une loi y porte atteinte aux rapports de pouvoirs. Si on a avanc√© l'id√©e que les modes alternatifs de solution des conflits offrent aux parties faibles et d√©favoris√©es l'occasion de faire valoir leurs int√©r√™ts, on a aussi soutenu, √† l'inverse, qu'ils peuvent permettre √† des justiciables d√©j√† bien nantis, d'augmenter leurs pouvoirs, √©tant ainsi √† l'abri de l'influence r√©gulatrice des tribunaux √©tatiques. √Ä certains moments de l'histoire, les d√©munis peuvent m√™me manipuler √† leur avantage l'intervention √©tatique. Les voies non √©tatiques peuvent √©galement, en certaines circonstances particuli√®res, favoriser collectivement les membres de certains collectivit√©s dans lesquelles elles interviennent

    Customary Law in Common Law Systems

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    Summaries How can the idea of the ‚Äėrule of law‚Äô be made a reality for ordinary people in African countries where customary law still underpins popular experience of ‚Äėlaw as practice‚Äô? It is argued that the idea of law itself should include all non?state ‚Äėnormative orders‚Äô that are known, acceptable and pre?determined, as well as state law. What is called customary law is often closer to observed social norms (practised law) than the state law imported by colonialism, and indeed evolves in line with social and economic change, particularly in the field of land tenure. Any notion of the rule of law must support the institutions of customary law. One problem, however, is that in any country there are many different bodies of customary law particular to different localities, regions, cultures. This diversity must be both researched and recognised

    Novel algorithmic approach predicts tumor mutation load and correlates with immunotherapy clinical outcomes using a defined gene mutation set

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    BACKGROUND: While clinical outcomes following immunotherapy have shown an association with tumor mutation load using whole exome sequencing (WES), its clinical applicability is currently limited by cost and bioinformatics requirements. METHODS: We developed a method to accurately derive the predicted total mutation load (PTML) within individual tumors from a small set of genes that can be used in clinical next generation sequencing (NGS) panels. PTML was derived from the actual total mutation load (ATML) of 575 distinct melanoma and lung cancer samples and validated using independent melanoma (n‚ÄČ=‚ÄČ312) and lung cancer (n‚ÄČ=‚ÄČ217) cohorts. The correlation of PTML status with clinical outcome, following distinct immunotherapies, was assessed using the Kaplan‚ÄďMeier method. RESULTS: PTML (derived from 170 genes) was highly correlated with ATML in cutaneous melanoma and lung adenocarcinoma validation cohorts (R(2)‚ÄČ=‚ÄČ0.73 and R(2)‚ÄČ=‚ÄČ0.82, respectively). PTML was strongly associated with clinical outcome to ipilimumab (anti-CTLA-4, three cohorts) and adoptive T-cell therapy (1 cohort) clinical outcome in melanoma. Clinical benefit from pembrolizumab (anti-PD-1) in lung cancer was also shown to significantly correlate with PTML status (log rank P value‚ÄČ<‚ÄČ0.05 in all cohorts). CONCLUSIONS: The approach of using small NGS gene panels, already applied to guide employment of targeted therapies, may have utility in the personalized use of immunotherapy in cancer. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s12916-016-0705-4) contains supplementary material, which is available to authorized users

    Beyond BRAFV600: Clinical Mutation Panel Testing by Next-Generation Sequencing in Advanced Melanoma

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    The management of melanoma has evolved owing to improved understanding of its molecular drivers. To augment the current understanding of the prevalence, patterns, and associations of mutations in this disease, the results of clinical testing of 699 advanced melanoma patients using a pan-cancer next-generation sequencing (NGS) panel of hotspot regions in 46 genes were reviewed. Mutations were identified in 43 of the 46 genes on the panel. The most common mutations were BRAFV600 (36%), NRAS (21%), TP53 (16%), BRAFNon-V600 (6%), and KIT (4%). Approximately one-third of melanomas had >1 mutation detected, and the number of mutations per tumor was associated with melanoma subtype. Concurrent TP53 mutations were the most frequent events in tumors with BRAFV600and NRAS mutations. Melanomas with BRAFNon-V600mutations frequently harbored concurrent NRAS mutations (18%), which were rare in tumors with BRAFV600 mutations (1.6%). The prevalence of BRAFV600 and KIT mutations were significantly associated with melanoma subtypes, and BRAFV600 and TP53 mutations were significantly associated with cutaneous primary tumor location. Multiple potential therapeutic targets were identified in metastatic unknown primary and cutaneous melanomas that lacked BRAFV600and NRAS mutations. These results enrich our understanding of the patterns and clinical associations of oncogenic mutations in melanoma

    RORő≥t+ innate lymphoid cells promote lymph node metastasis of breast cancers

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    Cancer cells tend to metastasize first to tumor-draining lymph nodes, but the mechanisms mediating cancer cell invasion into the lymphatic vasculature remain little understood. Here, we show that in the human breast tumor microenvironment (TME), the presence of increased numbers of RORő≥t+ group 3 innate lymphoid cells (ILC3) correlates with an increased likelihood of lymph node metastasis. In a preclinical mouse model of breast cancer, CCL21-mediated recruitment of ILC3 to tumors stimulated the production of the CXCL13 by TME stromal cells, which in turn promoted ILC3‚Äďstromal interactions and production of the cancer cell motile factor RANKL. Depleting ILC3 or neutralizing CCL21, CXCL13, or RANKL was sufficient to decrease lymph node metastasis. Our findings establish a role for RORő≥t+ILC3 in promoting lymphatic metastasis by modulating the local chemokine milieu of cancer cells in the TME

    Youth work, agonistic democracy and transgressive enjoyment in England

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    Concerns abound in media and political commentary regarding the purported political apathy of youth. This chapter shares the narratives of active engagement with politics on the part of a number of young people, as part of their efforts to resist the threats to youth services posed by the discourses and practices of neoliberal austerity. The analysis in the chapter links the young people’s engagement to the tenets of agonistic models of democracy, namely pluralism, contestation and tragedy. The chapter concludes with consideration of the implications of participants’ narrated experiences for the study of politics and political engagement in coming years
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