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).

Improvements in the Assessment of Bacterial Viability and Killing

It is axiomatic that our planet is extensively inhabited by diverse micro-organisms such as bacteria, yet the absolute diversity of different bacterial species is widely held to be unknown. Different bacteria can be found from the depths of the oceans to the top of the mountains; even the air is more or less colonized by bacteria. Most bacteria are either harmless or even advantageous to human beings but there are also bacteria, which can cause severe infectious diseases or spoil the supplies intended for human consumption. Therefore, it is vitally important not only to be able to detect and enumerate bacteria but also to assess their viability and possible harmfulness. Whilst the growth of bacteria is remarkably fast under optimum conditions and easy to detect by cultural methods, most bacteria are believed to lie in stationary phase of growth in which the actual growth is ceased and thus bacteria may simply be undetectable by cultural techniques. Additionally, several injurious factors such as low and high temperature or deficiency of nutrients can turn bacteria into a viable but non-culturable state (VBNC) that cannot be detected by cultural methods. Thereby, various noncultural techniques developed for the assessment of bacterial viability and killing have widely been exploited in modern microbiology. However, only a few methods are suitable for kinetic measurements, which enable the real-time detection of bacterial growth and viability. The present study describes alternative methods for measuring bacterial viability and killing as well as detecting the effects of various antimicrobial agents on bacteria on a real-time basis. The suitability of bacterial (lux) and beetle (luc) luciferases as well as green fluorescent protein (GFP) to act as a marker of bacterial viability and cell growth was tested. In particular, a multiparameter microplate assay based on GFP-luciferase combination as well as a flow cytometric measurement based on GFP-PI combination were developed to perform divergent viability analyses. The results obtained suggest that the antimicrobial activities of various drugs against bacteria could be successfully measured using both of these methods. Specifically, the data reliability of flow cytometric viability analysis was notably improved as GFP was utilized in the assay. A fluoro-luminometric microplate assay enabled kinetic measurements, which significantly improved and accelerated the assessment of bacterial viability compared to more conventional viability assays such as plate counting. Moreover, the multiparameter assay made simultaneous detection of GFP fluorescence and luciferase bioluminescence possible and provided extensive information about multiple cellular parameters in single assay, thereby increasing the accuracy of the assessment of the kinetics of antimicrobial activities on target bacteria.

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.

Knowing What to Respond in the Future Does Not Cancel the Influence of Past Events

Everyday tasks seldom involve isolate actions but sequences of them. We can see whether previous actions influence the current one by exploring the response time to controlled sequences of stimuli. Specifically, depending on the response-stimulus temporal interval (RSI), different mechanisms have been proposed to explain sequential effects in two-choice serial response tasks. Whereas an automatic facilitation mechanism is thought to produce a benefit for response repetitions at short RSIs, subjective expectancies are considered to replace the automatic facilitation at longer RSIs, producing a cost-benefit pattern: repetitions are faster after other repetitions but they are slower after alternations. However, there is not direct evidence showing the impact of subjective expectancies on sequential effects. By using a fixed sequence, the results of the reported experiment showed that the repetition effect was enhanced in participants who acquired complete knowledge of the order. Nevertheless, a similar cost-benefit pattern was observed in all participants and in all learning blocks. Therefore, results of the experiment suggest that sequential effects, including the cost-benefit pattern, are the consequence of automatic mechanisms which operate independently of (and simultaneously with) explicit knowledge of the sequence or other subjective expectancies.

Keskisuuren teknologiayrityksen logistiikkaratkaisujen arviointi

Asiakkaat ovat nykyisin yhä tietoisempia tuotteen tuomasta arvosta. Uusiksi kilpailutekijöiksi ovat hinnan sijasta muodostumassa asiakaslähtöisyys, toiminnan laadukkuus ja yrityksen kyky synkronoida liiketoimintaprosesseja yhteistyössä asiakkaiden kanssa. Toimitusketjun hallinta on avainasemassa, kun pyritään saavuttamaan kilpailuetua uudessa kilpailutilanteessa. Yrityksien haasteeksi muodostuu koko arvoketjun kattavan strategisen yhteensopivuuden saavuttaminen sekä tasapainon löytäminen reagoivuuden ja tehokkuuden välille. Diplomityö käsittelee kohdeyrityksen nykyistä toimitusketjua ja kartoittaa kuinka eri logistiikkaratkaisut vaikuttaisivat yrityksen toimitusketjun materiaalivirtoihin ja kustannusrakenteeseen sekä kilpailukykyyn tulevaisuudessa. Työssä pyritään arvioimaan myös eri ratkaisujen vahvuuksia ja heikkouksia sekä käyttöönottoon liittyviä haasteita. Muutoksia on pyritty arvioimaan luomalla nykytilakuvauksen pohjalta simulointimalleja, joiden avulla voidaan mallintaa sekä materiaalivirtojen että kustannuksien muutoksia. Empiriaosassa on kuvattu eri logistiikkaratkaisujen vaikutukset materiaalivirtoihin ja logistiikkatoimintojen kokonaiskustannuksiin, sekä niiden edut ja haitat. Tämä mandollistaa eri logistiikkaratkaisujen arvioinnin ja tuo esille kuinka nykyistä toimitusketjua olisi kehitettävä, jotta kohdeyritys pystyy tulevaisuudessa parantamaan kilpailukykyään kustannustehokkaasti.

Boosting Future Prospects or Softening Promises of Success? The Use of Emphatics and Hedging in the Letter to Shareholders Sections of Annual Reports

Tämä pro gradu -tutkielma käsittelee yritysten vuosikertomusten Toimitusjohtajan katsaus -osioissa esiintyvää metatekstiä. Erityisenä tutkimuskohteena ovat yrityksen tulevaisuutta käsittelevät lauseet ja niissä käytetty interpersonaalinen metateksti, jonka avulla kirjoittaja pyrkii joko vahvistamaan (emphatics-keinoin) tai heikentämään (hedging-keinoin) ilmaisujensa vahvuutta ja lukijalle niiden kautta välittyvää kuvaa viestin varmuudesta ja vakuuttavuudesta. Sijoittajille suunnattu Toimitusjohtajan katsaus käsittelee yleensä yrityksen edellisen vuoden tulosta, taloudellista asemaa sekä tulevaisuudennäkymiä. Tutkimuksen tarkoituksena oli selvittää, vaikuttaako yrityksen taloudellinen menestys vuosikertomuksen tässä osiossa käytetyn metatekstin määrään ja laatuun. Tutkimuksen teoriaosuudessa käsitellään ensiksi lyhyesti vuosikertomuksia ja niiden parissa tehtyä aiempaa kielitieteellistä tutkimusta, minkä jälkeen perehdytään tarkemmin metatekstin sekä hedging- ja emphatics-keinojen määrittelyyn. Näissä osioissa apuna toimivat muunmuassa Hylandin (1998) ja Cromptonin (1997) tutkimukset. Tutkimusaineistossa esiintyvien metatekstilajien määrittelyssä ja tunnistamisessa käytettiin apuna pääosin Crismore & Farnsworthin (1990) ja Grabe & Kaplanin (1997) tutkimuksia. Tutkimuksen aineistona oli yhteensä 23 yhdentoista amerikkalaisen yrityksen vuosikertomusta. Ne käsittivät esimerkkejä kunkin yhtiön talouden kannalta sekä erityisen hyviltä että huonoilta vuosilta. Aineistosta löydetty interpersonaalinen metateksti luokiteltiin viiteen eri ryhmään: modaaliverbit, hedging-verbit, muut hedging-keinot, emphatics-keinot ja evaluatives-keinot (eli kirjoittajan tekstistään tekemät subjektiiviset huomiot ja arviot). Tulokset osoittivat, että metatekstin käytössä ilmeni melkoista vaihtelua yksittäisten yritysten ja niiden hyvien ja huonojen vuosien välillä. Nämä eroavuudet eivät kuitenkaan vaikuttaneet merkittävästi koko aineiston kattaviin keskivertolukuihin, joiden avulla pyrittiin selvittämään hyvien ja huonojen vuosien välisiä yleisiä eroja. Tutkimuksen perusteella voidaan todeta, että Toimitusjohtajan katsaus –osioiden viittaukset yhtiön tulevaisuuteen heijastavat tavallisesti kirjoittajan varmuutta yrityksen menestyksekkäästä tulevaisuudesta riippumatta siitä, minkälainen vuosikertomuksessa käsitelty vuosi on ollut yhtiölle taloudellisesti. Yleisesti ottaen yhtiön taloudellisen tilan ei siis havaittu vaikuttavan Toimitusjohtajan katsauksessa käytetyn metadiskurssin määrään tai laatuun.

Longitudinal monitoring of endogenous steroids in human serum by UHPLC-MS/MS as a tool to detect testosterone abuse in sports.

The detection of testosterone abuse in sports is routinely achieved through the 'steroidal module' of the Athlete Biological Passport by GC-MS(/MS) quantification of selected endogenous anabolic androgenic steroids (EAAS) from athletes' urines. To overcome some limitations of the "urinary steroid profile" such as the presence of confounding factors (ethnicity, enzyme polymorphism, bacterial contamination, and ethanol), ultrahigh performance liquid chromatography (UHPLC) measurements of blood concentrations of testosterone, its major metabolites, and precursors could represent an interesting and complementary strategy. In this work, two UHPLC-MS/MS methods were developed for the quantification of testosterone and related compounds in human serum, including major progestogens, corticoids, and estrogens. The validated methods were then used for the analyses of serum samples collected from 19 healthy male volunteers after oral and transdermal testosterone administration. Results from unsupervised multiway analysis allowed variations of target analytes to be assessed simultaneously over a 96-h time period. Except for alteration of concentration values due to the circadian rhythm, which concerns mainly corticosteroids, DHEA, and progesterone, significant variations linked to the oral and transdermal testosterone administration were observed for testosterone, DHT, and androstenedione. As a second step of analysis, the longitudinal monitoring of these biomarkers using intra-individual thresholds showed, in comparison to urine, significant improvements in the detection of testosterone administration, especially for volunteers with del/del genotype for phase II UGT2B17 enzyme, not sensitive to the main urinary marker, T/E ratio. A substantial extension of the detection window after transdermal testosterone administration was also observed in serum matrix. The longitudinal follow-up proposed in this study represents a first example of 'blood steroid profile' in doping control analysis, which can be proposed in the future as a complement to the 'urinary module' for improving steroid abuse detection capabilities.

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.

Blood pressure reductions following catheter-based renal denervation are not related to improvements in adherence to antihypertensive drugs measured by urine/plasma toxicological analysis.

Renal denervation can reduce blood pressure in patients with uncontrolled hypertension. The adherence to prescribed antihypertensive medication following renal denervation is unknown. This study investigated adherence to prescribed antihypertensive treatment by liquid chromatography-high resolution tandem mass spectrometry in plasma and urine at baseline and 6 months after renal denervation in 100 patients with resistant hypertension, defined as baseline office systolic blood pressure ≥140 mmHg despite treatment with ≥3 antihypertensive agents. At baseline, complete adherence to all prescribed antihypertensive agents was observed in 52 patients, 46 patients were partially adherent, and two patients were completely non-adherent. Baseline office blood pressure was 167/88 ± 19/16 mmHg with a corresponding 24-h blood pressure of 154/86 ± 15/13 mmHg. Renal denervation significantly reduced office and ambulatory blood pressure at 6-month follow-up by 15/5 mmHg (p < 0.001/p < 0.001) and 8/4 mmHg (p < 0.001/p = 0.001), respectively. Mean adherence to prescribed treatment was significantly reduced from 85.0 % at baseline to 80.7 %, 6 months after renal denervation (p = 0.005). The blood pressure decrease was not explained by improvements in adherence following the procedure. Patients not responding to treatment significantly reduced their drug intake following the procedure. Adherence was highest for angiotensin-converting enzyme inhibitors/angiotensin receptor blockers and beta blockers (>90 %) and lowest for vasodilators (21 %). In conclusion, renal denervation can reduce office and ambulatory blood pressure in patients with resistant hypertension despite a significant reduction in adherence to antihypertensive treatment after 6 months.

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.