Race Yourselves: A Longitudinal Exploration of Self-Competition Between Past, Present, and Future Performances in a VR Exergame

Participating in competitive races can be a thrilling experience for athletes, involving a rush of excitement and sensations of flow, achievement, and self-fulfilment. However, for non-athletes, the prospect of competition is often a scary one which affects intrinsic motivation negatively, especially for less fit, less competitive individuals. We propose a novel method making the positive racing experience accessible to non-athletes using a high-intensity cycling VR exergame: by recording and replaying all their previous gameplay sessions simultaneously, including a projected future performance, players can race against a crowd of "ghost" avatars representing their individual fitness journey. The experience stays relevant and exciting as every race adds a new competitor. A longitudinal study over four weeks and a cross-sectional study found that the new method improves physical performance, intrinsic motivation, and flow compared to a non-competitive exergame. Additionally, the longitudinal study provides insights into the longer-term effects of VR exergames

Grey wolf genomic history reveals a dual ancestry of dogs

The grey wolf (Canis lupus) was the first species to give rise to a domestic population, and they remained widespread throughout the last Ice Age when many other large mammal species went extinct. Little is known, however, about the history and possible extinction of past wolf populations or when and where the wolf progenitors of the present-day dog lineage (Canisfamiliaris) lived(1-8). Here we analysed 72 ancient wolf genomes spanning the last 100,000 years from Europe, Siberia and North America. We found that wolf populations were highly connected throughout the Late Pleistocene, with levels of differentiation an order of magnitude lower than they are today. This population connectivity allowed us to detect natural selection across the time series, including rapid fixation of mutations in the gene IFT8840,000-30,000 years ago. We show that dogs are overall more closely related to ancient wolves from eastern Eurasia than to those from western Eurasia, suggesting a domestication process in the east. However, we also found that dogs in the Near East and Africa derive up to half of their ancestry from a distinct population related to modern southwest Eurasian wolves, reflecting either an independent domestication process or admixture from local wolves. None of the analysed ancient wolf genomes is a direct match for either of these dog ancestries, meaning that the exact progenitor populations remain to be located.Peer reviewe

A Roadmap for HEP Software and Computing R&D for the 2020s

Particle physics has an ambitious and broad experimental programme for the coming decades. This programme requires large investments in detector hardware, either to build new facilities and experiments, or to upgrade existing ones. Similarly, it requires commensurate investment in the R&D of software to acquire, manage, process, and analyse the shear amounts of data to be recorded. In planning for the HL-LHC in particular, it is critical that all of the collaborating stakeholders agree on the software goals and priorities, and that the efforts complement each other. In this spirit, this white paper describes the R&D activities required to prepare for this software upgrade.Peer reviewe

Sex difference and intra-operative tidal volume: Insights from the LAS VEGAS study

BACKGROUND: One key element of lung-protective ventilation is the use of a low tidal volume (VT). A sex difference in use of low tidal volume ventilation (LTVV) has been described in critically ill ICU patients.OBJECTIVES: The aim of this study was to determine whether a sex difference in use of LTVV also exists in operating room patients, and if present what factors drive this difference.DESIGN, PATIENTS AND SETTING: This is a posthoc analysis of LAS VEGAS, a 1-week worldwide observational study in adults requiring intra-operative ventilation during general anaesthesia for surgery in 146 hospitals in 29 countries.MAIN OUTCOME MEASURES: Women and men were compared with respect to use of LTVV, defined as VT of 8 ml kg-1 or less predicted bodyweight (PBW). A VT was deemed 'default' if the set VT was a round number. A mediation analysis assessed which factors may explain the sex difference in use of LTVV during intra-operative ventilation.RESULTS: This analysis includes 9864 patients, of whom 5425 (55%) were women. A default VT was often set, both in women and men; mode VT was 500 ml. Median [IQR] VT was higher in women than in men (8.6 [7.7 to 9.6] vs. 7.6 [6.8 to 8.4] ml kg-1 PBW, P < 0.001). Compared with men, women were twice as likely not to receive LTVV [68.8 vs. 36.0%; relative risk ratio 2.1 (95% CI 1.9 to 2.1), P < 0.001]. In the mediation analysis, patients' height and actual body weight (ABW) explained 81 and 18% of the sex difference in use of LTVV, respectively; it was not explained by the use of a default VT.CONCLUSION: In this worldwide cohort of patients receiving intra-operative ventilation during general anaesthesia for surgery, women received a higher VT than men during intra-operative ventilation. The risk for a female not to receive LTVV during surgery was double that of males. Height and ABW were the two mediators of the sex difference in use of LTVV.TRIAL REGISTRATION: The study was registered at Clinicaltrials.gov, NCT01601223

31st Annual Meeting and Associated Programs of the Society for Immunotherapy of Cancer (SITC 2016) : part two

Background The immunological escape of tumors represents one of the main ob- stacles to the treatment of malignancies. The blockade of PD-1 or CTLA-4 receptors represented a milestone in the history of immunotherapy. However, immune checkpoint inhibitors seem to be effective in specific cohorts of patients. It has been proposed that their efficacy relies on the presence of an immunological response. Thus, we hypothesized that disruption of the PD-L1/PD-1 axis would synergize with our oncolytic vaccine platform PeptiCRAd. Methods We used murine B16OVA in vivo tumor models and flow cytometry analysis to investigate the immunological background. Results First, we found that high-burden B16OVA tumors were refractory to combination immunotherapy. However, with a more aggressive schedule, tumors with a lower burden were more susceptible to the combination of PeptiCRAd and PD-L1 blockade. The therapy signifi- cantly increased the median survival of mice (Fig. 7). Interestingly, the reduced growth of contralaterally injected B16F10 cells sug- gested the presence of a long lasting immunological memory also against non-targeted antigens. Concerning the functional state of tumor infiltrating lymphocytes (TILs), we found that all the immune therapies would enhance the percentage of activated (PD-1pos TIM- 3neg) T lymphocytes and reduce the amount of exhausted (PD-1pos TIM-3pos) cells compared to placebo. As expected, we found that PeptiCRAd monotherapy could increase the number of antigen spe- cific CD8+ T cells compared to other treatments. However, only the combination with PD-L1 blockade could significantly increase the ra- tio between activated and exhausted pentamer positive cells (p= 0.0058), suggesting that by disrupting the PD-1/PD-L1 axis we could decrease the amount of dysfunctional antigen specific T cells. We ob- served that the anatomical location deeply influenced the state of CD4+ and CD8+ T lymphocytes. In fact, TIM-3 expression was in- creased by 2 fold on TILs compared to splenic and lymphoid T cells. In the CD8+ compartment, the expression of PD-1 on the surface seemed to be restricted to the tumor micro-environment, while CD4 + T cells had a high expression of PD-1 also in lymphoid organs. Interestingly, we found that the levels of PD-1 were significantly higher on CD8+ T cells than on CD4+ T cells into the tumor micro- environment (p < 0.0001). Conclusions In conclusion, we demonstrated that the efficacy of immune check- point inhibitors might be strongly enhanced by their combination with cancer vaccines. PeptiCRAd was able to increase the number of antigen-specific T cells and PD-L1 blockade prevented their exhaus- tion, resulting in long-lasting immunological memory and increased median survival

Dynamic Difficulty Adjustment Impact on Players' Confidence

International audienceDifficulty is one of the major motivational pull of video games, and thus many games use Dynamic Difficulty Adjustment (DDA) systems to improve the game experience. This paper describes our research investigating the influence of DDA systems on player's confidence, evaluated using an in-game bet system. Our hypothesis is that DDA systems may lead players to overconfidence, revealed by an overestimation of their success chances when betting. This boost of confidence may be a part of the positive impact of DDA systems on the quality of game experience. We explain our method to evaluate player's confidence and implement it into three games related to logical, motor and sensory difficulties. We describe two experimental conditions where difficulty is either randomly chosen or adapted using a DDA algorithm. Results show how DDA systems can lead players to high level of overconfidence

A Case of Infectious Laryngotracheitis in an Organic Broiler Chicken Farm in Greece

Infectious laryngotracheitis is an economically significant viral disease of chickens, that mainly affects the upper respiratory tract, and is present worldwide. This case reports the first outbreak of infectious laryngotracheitis in a four-week-old organic broiler farm and surrounding flocks in Greece, with typical clinical symptoms and lesions, allegedly provoked by a wild strain of infectious laryngotracheitis virus. Our findings contradict the general perception indicating that the disease appears mainly in older birds and that vaccine strains are the primary cause of infectious laryngotracheitis outbreaks in most continents. A recombinant vectored vaccine was administered, supplementary to biosecurity measures, containing the viral spread. The responsible strain was potentially circulating in the area; therefore, an industry-wide holistic approach was applied, including the vaccination of neighboring broilers and breeders with the same vaccine, the rapid molecular diagnosis of the disease, and strict biosecurity protocols. The results of this holistic effort were effective because, following the application of vaccine and management protocols, manifestations of the disease in regional flocks dropped significantly, and there was no recurrence to date. These findings suggest that vaccination protocols should be modified, especially for organic broilers, to include vaccination against infectious laryngotracheitis

Permeability of the blood‐brain barrier induced by 915 MHz electromagnetic radiation, continuous wave and modulated at 8, 16, 50, and 200 Hz

Biological effects of electromagnetic fields (EMF) on the blood‐brain barrier (BBB) can be studied in sensitive and specific models. In a previous investigation of the permeability of the blood‐brain barrier after exposure to the various EMF‐components of proton magnetic resonance imaging (MRI), we found that the exposure to MRI induced leakage of Evans Blue labeled proteins normally not passing the BBB of rats [Salford et al. (1992), in: Resonance Phenomena in Biology, Oxford University Press, pp. 87–91]. In the present investigation we exposed male and female Fischer 344 rats in a transverse electromagnetic transmission line chamber to microwaves of 915 MHz as continuous wave (CW) and pulse‐modulated with repetition rates of 8, 16, 50, and 200 s−1. The specific energy absorption rate (SAR) varied between 0.016 and 5 W/kg. The rats were not anesthetized during the 2‐hour exposure. All animals were sacrificed by perfusion‐fixation of the brains under chloral hydrate anesthesia about 1 hour after the exposure. The brains were perfused with saline for 3–4 minutes, and thereafter fixed in 4% formaldehyde for 5–6 minutes. Central coronal sections of the brains were dehydrated and embedded in paraffin and sectioned at 5 μm. Albumin and fibrinogen were demonstrated immunohistochemically. The results show albumin leakage in 5 of 62 of the controls and in 56 of 184 of the animals exposed to 915 MHz microwaves. Continuous wave resulted in 14 positive findings of 35, which differ significantly from the controls (P = 0.002). With pulsed 915 MHz microwaves with repetition rates of 200, 50, 16, and 8 s−1, 42 of 149 were positive, which is highly significant at the P = 0.001 level. This reveals that both CW and pulsed 915 MHz microwaves have the potential to open up the BBB for albumin passage. However, there is no significant difference between continuous and pulsed 915 MHz microwaves in this respect. The frequency of occurrence of extravasates (26%) was found to be independent of SAR for SAR < 2.5 W/kg, but rose significantly for the higher SAR values (to 43%). The question of whether the opening of the blood‐brain barrier constitutes a health hazard demands further investigation. © 1994 Wiley‐Liss, Inc