Present standards and future perspectives in the treatment of metastatic non-small cell lung cancer.

The development of novel effective immunotherapeutic agents and early clinical data hinting at significant activity in non-small cell lung cancer (NSCLC) has introduced yet another player in the field of management of advanced disease. At present, first-line cytotoxic chemotherapy is generally withheld pending results of molecular testing for any actionable genetic alteration that could lead to targeted treatment, and in their absence chemotherapy is prescribed as a default therapy. Phase III trials comparing head-to-head immune checkpoint inhibitors with standard platinum-based doublet chemotherapy are underway. Second-line chemotherapy is likewise being challenged in phase III trials, one of which having recently reported positive results in advanced squamous cell carcinoma. In tumors harboring actionable transforming genetic alterations such as EGFR mutations and ALK rearrangements, second- and third-generation inhibitors allow for multiple lines of targeted treatment beyond initial resistance, postponing the use of cytotoxic chemotherapy to very late lines of therapy. Chemotherapy as a longstanding but still present standard of care capable of prolonging survival, improving quality of life, and relieving symptoms sees its role increasingly restricted to clinical, immunological, and molecular subsets of patients where its activity and efficacy have never been tested prospectively.

Studying social interactions through immersive virtual environment technology: Virtues, pitfalls, and future challenges

Thegoalofthepresentreviewistoexplainhowimmersivevirtualenvironmenttechnology(IVET)canbeusedforthestudyofsocialinteractionsandhowtheuseofvirtualhumansinimmersivevirtualenvironmentscanadvanceresearchandapplicationinmanydifferentfields.Researchersstudyingindividualdifferencesinsocialinteractionsaretypicallyinterestedinkeepingthebehaviorandtheappearanceoftheinteractionpartnerconstantacrossparticipants.WithIVETresearchershavefullcontrolovertheinteractionpartners,canstandardizethemwhilestillkeepingthesimulationrealistic.Virtualsimulationsarevalid:growingevidenceshowsthatindeedstudiesconductedwithIVETcanreplicatesomewell-knownfindingsofsocialpsychology.Moreover,IVETallowsresearcherstosubtlymanipulatecharacteristicsoftheenvironment(e.g.,visualcuestoprimeparticipants)orofthesocialpartner(e.g.,his/herrace)toinvestigatetheirinfluencesonparticipants'behaviorandcognition.Furthermore,manipulationsthatwouldbedifficultorimpossibleinreallife(e.g.,changingparticipants'height)canbeeasilyobtainedwithIVET.Besidetheadvantagesfortheoreticalresearch,weexplorethemostrecenttrainingandclinicalapplicationsofIVET,itsintegrationwithothertechnologies(e.g.,socialsensing)andfuturechallengesforresearchers(e.g.,makingthecommunicationbetweenvirtualhumansandparticipantssmoother).

Circulating microRNAs: The Future of Biomarkers in Anti-doping Field.

microRNAs (miRNAs) are small non-coding RNAs that regulate various biological processes. Cell-free miRNAs have been proposed as biomarkers of disease, including diagnosis, prognosis, and monitoring of treatment responses. These circulating miRNAs are highly stable in several body fluids, including plasma and serum; hence, in view of their potential use as novel, non-invasive biomarkers, the profiles of circulating miRNAs have been explored in the field of anti-doping. This chapter describes the enormous potential of circulating miRNAs as a new class of biomarkers for the detection of doping substances, and highlights the advantages of measuring these stable species over other methods that have already been implemented in anti-doping regimes. Incorporating longitudinal measurements of circulating miRNAs into the Athlete Biological Passport is proposed as an efficient strategy for the implementation of these new biomarkers. Furthermore, potential challenges related to the transition of measurements of circulating miRNAs from research settings to practical anti-doping applications are presented.

Conclusions and future directions for sports events management scholarship

The book adopts a unique stakeholder perspective, structured around the groups and individuals who have an interest in and co-create sports events, including organising committees, promoters, sport organisations, spectators, community groups, sponsors, host governments, the media and NGOs. Each chapter addresses a specific stakeholder, defines that stakeholder and its relationships with sports events, describes the managerial requirements for a successful event, assesses current research and directions for future research, and outlines the normative dimensions of stakeholder engagement (such as sustainability and legacy)

Future perspectives in melanoma research: meeting report from the "Melanoma Bridge": Napoli, December 3rd-6th 2014.

The fourth "Melanoma Bridge Meeting" took place in Naples, December 3-6th, 2014. The four topics discussed at this meeting were: Molecular and Immunological Advances, Combination Therapies, News in Immunotherapy, and Tumor Microenvironment and Biomarkers. Until recently systemic therapy for metastatic melanoma patients was ineffective, but recent advances in tumor biology and immunology have led to the development of new targeted and immunotherapeutic agents that prolong progression-free survival (PFS) and overall survival (OS). New therapies, such as mitogen-activated protein kinase (MAPK) pathway inhibitors as well as other signaling pathway inhibitors, are being tested in patients with metastatic melanoma either as monotherapy or in combination, and all have yielded promising results. These include inhibitors of receptor tyrosine kinases (BRAF, MEK, and VEGFR), the phosphatidylinositol 3 kinase (PI3K) pathway [PI3K, AKT, mammalian target of rapamycin (mTOR)], activators of apoptotic pathway, and the cell cycle inhibitors (CDK4/6). Various locoregional interventions including radiotherapy and surgery are still valid approaches in treatment of advanced melanoma that can be integrated with novel therapies. Intrinsic, adaptive and acquired resistance occur with targeted therapy such as BRAF inhibitors, where most responses are short-lived. Given that the reactivation of the MAPK pathway through several distinct mechanisms is responsible for the majority of acquired resistance, it is logical to combine BRAF inhibitors with inhibitors of targets downstream in the MAPK pathway. For example, combination of BRAF/MEK inhibitors (e.g., dabrafenib/trametinib) have been demonstrated to improve survival compared to monotherapy. Application of novel technologies such sequencing have proven useful as a tool for identification of MAPK pathway-alternative resistance mechanism and designing other combinatorial therapies such as those between BRAF and AKT inhibitors. Improved survival rates have also been observed with immune-targeted therapy for patients with metastatic melanoma. Immune-modulating antibodies came to the forefront with anti-CTLA-4, programmed cell death-1 (PD-1) and PD-1 ligand 1 (PD-L1) pathway blocking antibodies that result in durable responses in a subset of melanoma patients. Agents targeting other immune inhibitory (e.g., Tim-3) or immune stimulating (e.g., CD137) receptors and other approaches such as adoptive cell transfer demonstrate clinical benefit in patients with melanoma as well. These agents are being studied in combination with targeted therapies in attempt to produce longer-term responses than those more typically seen with targeted therapy. Other combinations with cytotoxic chemotherapy and inhibitors of angiogenesis are changing the evolving landscape of therapeutic options and are being evaluated to prevent or delay resistance and to further improve survival rates for this patient population. This meeting's specific focus was on advances in combination of targeted therapy and immunotherapy. Both combination targeted therapy approaches and different immunotherapies were discussed. Similarly to the previous meetings, the importance of biomarkers for clinical application as markers for diagnosis, prognosis and prediction of treatment response was an integral part of the meeting. The overall emphasis on biomarkers supports novel concepts toward integrating biomarkers into contemporary clinical management of patients with melanoma across the entire spectrum of disease stage. Translation of the knowledge gained from the biology of tumor microenvironment across different tumors represents a bridge to impact on prognosis and response to therapy in melanoma.

Robert Jütte (Ed.), Medical Pluralism. Past - Present - Future (Stuttgart, F. Steiner Verlag, 2013)

Initiée en anthropologie à la fin des années 1970, la notion de pluralisme médical se voit réappropriée par diverses disciplines des sciences humaines, à l'instar des treize contributions de cet ouvrage collectif édité par Robert Jütte. Historiens, sociologues et anthropologues y interviennent à la suite d'un colloque organisé en 2001 en Italie par l'Institut d'histoire de la médecine de la Fondation Robert Bosch et le Centre Italo-Tedesco pour l'Excellence européenne, en collaboration avec le Forum de dialogue Pluralismus in der Medizin. Encore très questionnée et souvent nuancée selon les contextes, la définition du pluralisme médical se situe quelque part entre le fait que différentes formes de soins existent simultanément et s'influencent les unes les autres, et le constat d'une popularité grandissante des médecines alternatives et complémentaires défiant l'hégémonie de la biomédecine - cette situation s'observant plus particulièrement dans les pays occidentaux. C'est dans ce dernier contexte que s'inscrit le volume, dont chacune des contributions examine le phénomène du pluralisme médical soit en Allemagne, en Italie, en France ou en Grande-Bretagne - avec une exception pour l'Inde. La profondeur diachronique adoptée par l'ouvrage, couvrant l'époque pré-moderne à nos jours, offre une exploration élargie des expériences thérapeutiques. Ainsi sont évoqués, d'une part, les tenants de la médecine dite orthodoxe ou conventionnelle, regroupant les praticiens officiels que sont les médecins académiques en première ligne, suivis des chirurgiens, barbiers, apothicaires et sages-femmes; d'autre part sont pris en compte les représentants des médecines complémentaires, alternatives, naturelles ou encore populaires - des homéopathes aux acupuncteurs en passant par les magnétiseurs et les magiciennes guérisseuses. La réflexion sur les concurrences et les complémentarités entre ces acteurs variés, qui fait consensus au sein des contributions, est développée sous divers aspects.

Predicting the future effectiveness of protected areas for bird conservation in Mediterranean ecosystems under climate change and novel fire regime scenarios

AimGlobal environmental changes challenge traditional conservation approaches based on the selection of static protected areas due to their limited ability to deal with the dynamic nature of driving forces relevant to biodiversity. The Natura 2000 network (N2000) constitutes a major milestone in biodiversity conservation in Europe, but the degree to which this static network will be able to reach its long-term conservation objectives raises concern. We assessed the changes in the effectiveness of N2000 in a Mediterranean ecosystem between 2000 and 2050 under different combinations of climate and land cover change scenarios. LocationCatalonia, Spain. MethodsPotential distribution changes of several terrestrial bird species of conservation interest included in the European Union's Birds Directive were predicted within an ensemble-forecasting framework that hierarchically integrated climate change and land cover change scenarios. Land cover changes were simulated using a spatially explicit fire-succession model that integrates fire management strategies and vegetation encroachment after the abandonment of cultivated areas as the main drivers of landscape dynamics in Mediterranean ecosystems. ResultsOur results suggest that the amount of suitable habitats for the target species will strongly decrease both inside and outside N2000. However, the effectiveness of N2000 is expected to increase in the next decades because the amount of suitable habitats is predicted to decrease less inside than outside this network. Main conclusionsSuch predictions shed light on the key role that the current N2000may play in the near future and emphasize the need for an integrative conservation perspective wherein agricultural, forest and fire management policies should be considered to effectively preserve key habitats for threatened birds in fire-prone, highly dynamic Mediterranean ecosystems. Results also show the importance of considering landscape dynamics and the synergies between different driving forces when assessing the long-term effectiveness of protected areas for biodiversity conservation.

Areas of high conservation value in Georgia: present and future threats by invasive alien plants

Georgia is known for its extraordinary rich biodiversity of plants, which may now be threatened due to the spread of invasive alien plants (IAP). We aimed to identify (i) the most prominent IAP out of 9 selected potentially invasive and harmful IAP IAP by predicting thetheir distribution of 9 selected IAP under current and future climate conditions in Georgia as well as in its 43 Protected Areas, as a proxy for areas of high conservation value and (ii) the Protected Areas most at risk due to these IAP. We used species distribution models based on 6 climate variables and then filtered the obtained distributions based on maps of soil and vegetation types, and on recorded occurrences, resulting into the predicted ecological distribution of the 9 IAP's at a resolution of 1km2. We foundOur habitat suitability analysis showed that Ambrosia artemisiifolia, (24% and 40%) Robinia pseudoacaia (14% and 19%) and Ailanthus altissima (9% and 11%) have the largest potential distribution are the most abundant (predicted % area covered)d) IAP, with Ailanthus altissima the potentially most increasing one over the next fifty years (from 9% to 13% and from 11% to 25%), for Georgia and the Protected Areas, respectively. Furthermore, our results show indicate two areas in Georgia that are under specifically high threat, i.e. the area around Tbilisi and an area in the western part of Georgia (Adjara), both at lower altitudes. Our procedure to identify areas of high conservation value most at risk by IAP has been applied for the first time. It will help national authorities in prioritizing their measures to protect Georgia's outstanding biodiversity from the negative impact of IAP.

Olympic social responsibility : a challenge for the future

Social responsibility, especially in the fields of education, society and peace, is one of the cornerstones of the olympic ideal and strategic vision (contribute to building a better world through sport). The article reviews the literature on organizational social responsibility (OSR) and the relationship between sport/olympism and OSR in order to examine the conditions governing the implementation and success of the International Olympic Committee's strategic vision. Several ways in which the IOC could promote a more ambitious and better-integrated social strategy: revise its performance model, notably evaluate and present in a social responsibility report; promote the adoption of OSR initiatives and strategies within the Olympic System from the bottom-up, rather than from the top-down; share best practices in the different countries for promoting and developing "sport for all"; create a World Agency for Development through Sport, or partnering and funding the international platform on sport and development; creating a World Agency for the International Governance of Sport. Two possible scenarios for the future of Olympic responsibility are finally discussed: strategy of "small steps" and a more ambitious local and global social strategy through sport and olympism.