Immunological aspects on prognosis in resectable cholangiocellular cancer

Background: Biliary tract cholangiocellular cancers, cholangiocarcinoma (CCA) and gallbladder cancer (GBC), are malignancies with poor prognosis. Even after resection surgery with curative intent, a majority of patients suffer recurrence, and median overall survival (OS) remains limited to approximately three years. To improve long-term survival, a better understanding of prognostic factors is needed to individualize treatment. Aims: Paper I – To evaluate the prognostic value of two preoperative inflammation-based prognostic scores, the Glasgow prognostic score (GPS) and the Modified Glasgow prognostic score (mGPS). Paper II – To evaluate prognostic factors and outcomes after hepatobiliary resection for perihilar CCA (pCCA) in patients with underlying primary sclerosing cholangitis (PSC), a chronic hepatobiliary inflammatory condition. Paper III – To identify specific immunologic prognostic markers and to further characterize the immune response in resectable biliary tract cancer. Paper IV – To systematically review the prognostic influence of multiple hepatic lesions in patients undergoing resection for intrahepatic CCA (iCCA), with stratification according to distribution and number of lesions. Methods: Paper I was a retrospective single-centre study, including patients undergoing surgery for iCCA, pCCA or GBC (Karolinska University Hospital 2009-2017). The primary outcome was OS, secondary outcome complications. Survival was analysed by the Kaplan- Meier method and Cox regression. Paper II was a retrospective multicentre cohort study including patients undergoing resection for pCCA at 21 centres (Europe, United States 2000-2020). The primary outcome variable was OS, secondary outcomes disease-free survival and postoperative complications. Survival was analysed by Kaplan-Meier method and Cox regression. Paper III was a retrospective single-centre cohort study, including patients undergoing surgery for suspected biliary tract cancer at Karolinska University Hospital (2009-2017). The primary outcome variable was OS. Plasma expression of immune-related proteins was analysed in prospectively collected biobank samples by Proximity Extension Assay. Survival associations were analysed by Cox regression. Tissue expression of identified markers and receptors/ligands was analysed in independent public cohorts. Paper IV was a systematic review and meta-analysis (Medline [Ovid] and Embase, 2010- 2021). Original articles with data on OS stratified for tumour distribution (satellite lesions/other multiple lesions) and/or tumour number were included. The study was preregistered in a public prospective register of systematic reviews and PRISMA 2020 reporting guidelines were followed. Results: In paper I, the GPS and the mGPS were independent prognostic factors for overall survival after resection for biliary tract cancer (GPS≥1 hazard ratio [HR] 2.35, 95% confidence interval [CI] 1.41-3.93, mGPS≥1 HR 1.68, 95% CI 1.05-2.68). The GPS, but not the mGPS, identified an intermediate risk group. In paper II, median OS was 33 months (95% CI 10-54 months) for patients with PSCassociated pCCA and 29 months (95% CI 26-32 months) for patients without underlying PSC. Patients with PSC-associated pCCA had a lower rate of well-differentiated tumours (3% vs. 16%, p=0.043), a higher rate of postoperative complications (71% vs. 44%, p=0.003) and similar 90-day mortality (12% vs 13%, p=1.00) In paper III, three proteins in preoperative plasma were independently associated with OS: TRAIL/TNFSF10 (HR 0.30, 95% CI 0.16-0.56), TIE2/TEK (HR 2.78, 95% CI 1.20-6.48) and CSF1/M-CSF (HR 4.02, 95% CI 1.40-11.59). TRAIL/TNFSF10 was a positive prognostic factor in iCCA and pCCA. CSF1/M-CSF was a negative prognostic factor in iCCA and GBC. TIE2/TEK was a negative prognostic factor in GBC. In CCA tissue analysis, TRAIL-R1/TNFSFR10A receptor expression was higher in tumour and TRAIL/TNFSF10 was expressed by intratumoral lymphocytes, NK-cells and monocytes. CSF1/M-CSF was expressed by tumour-infiltrating CD8+ T-cells. In paper IV, OS was decreased for iCCA patients with satellite lesions (HR 1.89, 95% CI 1.67-2.13) and multiple lesions other than satellites (HR 2.41, 95% CI 1.72-3.37). Data stratified for tumour number was limited, but indicated increased risk per additional lesion. Conclusions: Preoperative systemic inflammatory markers were independent prognostic factors for OS after resection for BTC. Median OS after resection for pCCA was similar for patients with and without underlying PSC. Patients with PSC had a lower rate of well-differentiated tumours and a higher rate of complications. Three specific immunological protein markers in preoperative plasma were associated with OS in BTC, with disease-specific differences on subgroup analysis. iCCA-specific markers TRAIL/TNFSF10 and CSF1/M-CSF were expressed in tumour-infiltrating immune-cells. Satellite lesions, as well as multiple lesions other than satellites were negative prognostic factors in iCCA. The number of lesions was suggested to be a prognostic factor within the multiple lesion group

Evaluating clinical variation in traumatic brain injury data

Current methods of clinical guideline development have two large challenges: 1) there is often a long time-lag between the key results and publication into recommended best practice and 2) the measurement of adherence to those guidelines is often qualitative and difficult to standardise into measurable impact. In an age of ever-increasing volumes of accurate data captured at the bedside in specialist intensive care units, this thesis explores the possibility of constructing a technology that can interpret that data and present the results as a quantitative and immediate measure of guideline adherence. Applied to the Traumatic Brain Injury (TBI) domain, and specifically to the management of ICP and CPP, a framework is developed that makes use of process models to measure the adherence of clinicians to three specific TBI guidelines. By combining models constructed from physiological and treatment ICU data, and those constructed from guideline text, a distance is calculated between the two, and patterns of guideline adherence are inferred from this distance. The framework has been developed into an online application capable of producing adherence output on most standardised ICU datasets. This application has been applied to the Brain-IT and MIMIC III repositories and evaluated on the Philips ICCA bedside monitoring system. Patterns of guideline adherence are presented in a variety of ways including minute-by-minute windowing, tables of non-adherence instances, statistical distribution of instances, and a severity chart summarising the impact of non-adherence in a single number

El secreto profesional en el arbitraje internacional

It is more and more frequent that counsels from different jurisdictions are involved in preparing legal advice as companies offer their services and products abroad. This situation creates the risk that documents exchanged between clients and lawyers in one jurisdiction could be exhibited in future proceedings in another jurisdiction. Disclosure of certain information could determine several losses to businesses from prestige to lack of compensation that an unsuccessful case may entail. This type of legal chaos could diminish when business practitioners have autonomy to select the law for solution of future disputes, including the option to agree on the procedure to be followed by the adjudicator. This article analyses choice of law governing privilege by arbitrators as international arbitration is often referred to settle international disputes. Several soft law sources from arbitral institutional rules to the well-known IBA Rules on Evidence are scrutinized. It evaluates possible methods like the least protective privilege rule or the most protective privilege rules considering equal treatment. Finally, it explores the recent Unified Patent Court Rules as a source of inspiration for international arbitration.Cada vez resulta más frecuente que en el asesoramiento jurídico de las empresas se encuentren involucrados abogados de distintos países, dado que las empresas ofrecen sus bienes y servicios en el extranjero. Esta situación está sujeta al riesgo de que los documentos intercambiados entre clientes y abogados en un Estado pueda exhibirse en otro Estado en un procedimiento posterior. La exhibición de determinada información puede implicar diversas pérdidas para los empresarios desde el prestigio o la falta de compensación por los casos sin éxito. Este tipo de caos jurídico podría disminuir, ya que los empresarios tienen la opción de elegir la ley aplicable para la solución de sus controversias futuras, incluyendo la opción de acordar el procedimiento que seguirá el árbitro. Este artículo analiza la selección de la ley aplicable al secreto profesional por los árbitros, puesto que el arbitraje internacionalsuele ser elegido para resolver las controversias internacionales. Se estudian determinadas fuentes de Derecho blando desde las reglas de las instituciones arbitrales hasta las famosas Reglas de la IBA sobre la práctica de la prueba en el arbitraje internacional. También se analizan determinados métodos como el de la regla menos protectora o el de la más protectora, considerando el principio de igualdad de trato. Finalmente, se exploran las recientes Reglas de Procedimiento del Tribunal Unificado de Patentes como fuente de inspiración para el arbitraje internacional

Arbitration in merger and acquisition transactions : problem of consent in parallel proceedings and in the transfer of arbitration agreements in merger and acquisition arbitration

PhDMerger and acquisition (M&A) transactions have increased dramatically both in number and volume around the world in the last decades. Further to these increases, disputes regarding M&A transactions are often referred to arbitration as a consensual and private mechanism which is flexible, given the freedom of the parties to select arbitrators and to adjust the process according to their needs. This study undertakes to address and examine the long and complex processes in merger and acquisition transactions in light of the emerging preference for utilising arbitration in disputes arising therein. Therefore, M&A arbitration faces certain difficulties in coping with every dispute during the transaction, a number of which the author seeks to underline. In the thesis, two main problems of arbitration in M&A Transactions have been covered. Firstly, the problem of consent in consolidation of parallel proceedings during M&A transactions, and, secondly, parties consent validating arbitration agreements/clauses in “assignment” or “succession” after M&A transactions have been completed. The very approach of the thesis proposes whether academic analysis of the subject matter can be best conducted by separation along the many phases of the long and complex process of M&A and whether it is fruitful to examine these phases individually to obtain the greatest insight. Following the dissection of the different phases of M&A transactions, the nature and operation of arbitration in possible disputes arising out of different phases of M&A has been studied. It is also argued that the utilisation of arbitration will and should provide some ideas toward clarifying the content of consent of parties to a transaction. In demarcating the phases and critical stages in M&A transactions, perspective of the problems posed by parallel proceedings is enhanced. Developing on this rich background, argument develops the idea that the logic of consolidation in arbitration and can have pragmatic application to different alternative dispute resolution (ADR) clauses too. The expansive application of consent in M&A arbitration will be tested against those different ADR methods which do not have a binding effect. On the subject of consolidation in M&A transactions, it will be argued that it is necessary not only to focus on the intention of parties, but it is also unavoidable to concentrate on surrounding relevant facts arising in different phases of M&A transactions, given the recent doctrinal developments in academia and practice. Diverging views which have emerged in order to determine consent are explored alongside their respective theories of consent. The specific importance of consent in the transfer of arbitration agreements has been examined in respect of assignment and succession. The existing rules and approaches outlined in many publications will be challenged, and arguments against their automatic application in M&A transactions will be presented in favour of an expansive approach paying attention to the fluency of facts, similar to that employed in consolidation of parallel proceedings. In examining whether current regulation is suitable given the popular emergence of M&A arbitration, the author will propose how deficiencies and inconsistencies in the area can be rectified looking forward in the form of guidelines.ARKAS Holding

Journal of Education Innovation and Communication: Redefining Communication: Social Media and the Age of Innovation

The publications of the Communication Institute of Greece, such as the “Journal of Education, Innovation, and Communication (JEICOM)”, are open access without any costs for the authors or the readers. JEICOM is a Fully Peer-Reviewed, Open Access journal, publishing articles from all areas of education, innovation and communication, independent of the events organized by the Communication Institute of Greece. JEICOM’s scope is to provide a free and open platform to academics, researchers, professionals, and postgraduate students to communicate and share knowledge in the form of high quality empirical and theoretical research that is of high interest not only for academic readers but also for practitioners and professionals. JEICOM welcomes theoretical, conceptual and empirical original research papers, case studies, book reviews that demonstrate the innovative and dynamic spirit for the education and communication sciences, from researchers, scholars, educators, policy-makers, and practitioners in education, communication, and related fields. Articles that show scholarly depth, breadth or richness of different aspects of social pedagogy are particularly welcome. The numerous papers presented every year during the conferences organized by the Communication Institute of Greece, enables us to have access to a plethora of papers. Following a rigorous peer- review process, only a selection of these papers submitted is published biannually. In addition, to the papers presented in the Institute’s conference, we do encourage independent submissions of papers too. Nevertheless, before you submit, please make sure to respect the guidelines and templates provided. The current special issue of the “Journal of Education, Innovation, and Communication (JEICOM)”, is our First Special Issue (December 2019). We consider that education and fruitful exchange can improve our lives with the view to nurture intercultural communication. Academics can contribute significantly to the quality of the educational experience and help educate, communicate, exchange, meet new cultures, create and collaborate! We wish you an excellent reading and for the year to come soon, 2020, Health, Love, Knowledge, Education, Prosperity, Communication and Exchange

Arbitration and third parties.

PhDModern international transactions have become extremely complicated, requiring the participation of several parties for the delivery of large-scale projects. However. multiparty commercial projects are invariably executed through several bilateral contracts providing for bilateral dispute resolution arrangements. Some of the contracts might include a jurisdiction clause, certain others might provide for arbitration, while others may not contain any dispute resolution provisions at all. This practice leads to "jurisdictional fragmentation of the multiparty commercial project" where the several parties of a single business plan will fall under the jurisdiction of different adjudicatory fora. Thus. a dispute arising between two persons bound by an arbitration agreement in connection with the multiparty project will have to be resolved exclusively by arbitration between these two parties. Other persons cannot take part in the resolution of the dispute, even if they play an active role in the actual business project. and thus have an interest in the outcome of the dispute. These persons will remain third parties, both to the arbitration agreement and the arbitral award. This study focuses on the role and the interests of the wide group of third parties exhibiting an interest in the dispute pending before a tribunal between two genuine parties. The thesis, in particular, examines whether arbitration agreements can affect persons which are not contractually bound by these agreements. In addition, the thesis explores whether arbitral awards can affect persons that have not participated in the arbitration proceedings The thesis challenges the prevailing contractual approach to the issue of arbitration, focusing exclusively on the contractual characteristics of arbitration ag eements. According to this view, the main question is whether a non-signatory can be contractually bound by an arbitration agreement. The study demonstrates that focusing exclusively on the contractual nature of arbitration agreements obscures the real issue here, which is whether arbitration agreements may have any jurisdictional implications vis-a-vis `third parties'. Accordingly, the thesis takes a jurisdictional approach, and argues that the discussion should be focused on the dispute and on any implications this may have to third parties, rather than on the requirement of consent to arbitration agreements. Regarding the effect of arbitral awards on third parties, the thesis argues for a third-party effect of arbitral awards specially designed for the needs of international arbitration. More specifically, the case is made for the application of an arbitral effect different from that of res judicata, both in terms of quality and intensity, but that is nevertheless conclusive. It is also suggested that the third party effect of an arbitral award should be analogous to the degree of substantive association between the genuine and the false third parties. This is consistent with the basic premise of the whole thesis: the relations between several parties, in terms of jurisdiction and more generally in arbitration procedure, should correspond to the extent of association between those parties, in terms of substantive rights, interests and liability

Development of genomic resources in pigeonpea (Cajanus cajan L.Millspaugh)

This study reports generation of large-scale genomic resources for pigeonpea, a so-called 'orphan crop species' of the semi-arid tropic regions. A set of 88.860 BAC (bacterial anificial chromosomes)-end sequences (BESs) were generated after constructing two BAC libraries by using Hindlll (34.560 clones) and BamHl (34.560 clones) restriction enzymes. A total of 3,072 novel SSR primer pairs were synthesized and tested for length polymorphism on two parental genotypes (ICP 28 and ICPW 94). In addition. Roche FLXl454 sequencing was carried out on a normalized cDNA pool prepared from 31 tissues and produced 494.353 shon transcript reads (STRs). Cluster analysis of these STRs. together with 10.817 Sanger ESTs, resulted in 127.754 pigeonpea transcript assemblies (CcTAs). Additionally. Illurnina 1G sequencing was performed on four parental genotypes of two mapping populations and a set of 7.453 SNPs were identified. Based on BES-SSR markers, the first SSR-based genetic map comprising of 239 loci was developed for this previously uncharacterized genome. In summary. while BAC libraries, BESs and CcTAs should be useful for genomics studies. BES-SSR. SNP markers, and the genetic map should be very useful for linking the genetic map with a future physical map as well as for molecular breeding in pigeonpea