Optimal Pacing for Running 400 m and 800 m Track Races

Physicists seeking to understand complex biological systems often find it rewarding to create simple "toy models" that reproduce system behavior. Here a toy model is used to understand a puzzling phenomenon from the sport of track and field. Races are almost always won, and records set, in 400 m and 800 m running events by people who run the first half of the race faster than the second half, which is not true of shorter races, nor of longer. There is general agreement that performance in the 400 m and 800 m is limited somehow by the amount of anaerobic metabolism that can be tolerated in the working muscles in the legs. A toy model of anaerobic metabolism is presented, from which an optimal pacing strategy is analytically calculated via the Euler-Lagrange equation. This optimal strategy is then modified to account for the fact that the runner starts the race from rest; this modification is shown to result in the best possible outcome by use of an elementary variational technique that supplements what is found in undergraduate textbooks. The toy model reproduces the pacing strategies of elite 400 m and 800 m runners better than existing models do. The toy model also gives some insight into training strategies that improve performance.Comment: 14 pages, 4 figures, submitted to the American Journal of Physic

Ліберали України та вибори до і думи

Cytokine concentrations in biological fluids are widely used markers for activation of immunological processes. Confirming the reproducibility of measurements is important, especially in longitudinal or multicenter studies where time between analyses or different analyzing laboratories increases the intra-assay variability. In this study, the reproducibility of the cytokine analysis conducted with different assay platforms was studied by comparing the results of two cytokines [interleukin (IL)-6 in serum and nasal lavage fluid (NAL) and IL-8 in NAL] analyzed with Meso Scale Discovery (MSD) ultra-sensitive single and multiplex assay kits (n = 76). In addition, the difference in cytokine levels between two biological sample matrices was studied by comparing the results of altogether 9 cytokines [IL-6, IL-2, IL-8, IL12p70, IL-1β, granulocyte–macrophage colony-stimulating factor (GM-CSF), interferon (IFN)γ, IL-10 and tumor necrosis factor (TNF)α] measured from serum and NAL of the same study subjects (n = 460). The results show that the cytokine concentrations analyzed with single and multiplex assays are concordant but not equal. Comparison of the different matrices revealed that cytokine concentrations in serum do not correspond with concentrations detected in nasal lavage fluid. It can be concluded that comparability of the results from single and multiplex analysis of cytokines is high, but the concentrations should not be compared directly with each other. The differences between concentrations analyzed from serum and nasal lavage fluid indicate that the levels are specific for each matrix and represent distinct immunological conditions. (aut.ref.

Targeted Reinforcement of Macrophage Reprogramming Toward M2 Polarization by IL-4-Loaded Hyaluronic Acid Particles

Alteration of macrophage polarization from inflammatory (M1) to anti-inflammatory (M2) phenotype can have striking implications for the regeneration of injured tissues, treatment of inflammatory diseases, and relief of autoimmune disorders. Although certain cytokines like interleukin (IL)-4 and IL-13 are capable of inducing M2 macrophage polarization, their therapeutic potential in vivo is suffering from low efficacy due to their instability and poor access to target cells. Here, we report the synthesis of IL-4-loaded hyaluronic acid (HA) particle for the targeted delivery of cytokines through the high affinity of HA to CD44 receptors of macrophages. HA carriers composed of low, middle, and high molecular weight (MW) polymers were synthesized using divinyl sulfone (DVS) cross-linking. The MW of HA had a negligible effect on the physicochemical properties and biocompatibility of the macrophages, but as an indicative of M2 polarization, a significant change in the arginase-1 (Arg-1) activity, TNF-a release, and IL-10 secretion was observed for the HA particles prepared with high MW polymers. Therefore, these particles were loaded with IL-4 for simultaneous macrophage targeting and M1 to M2 reprogramming, evidenced by a remarkable increase in the Arg-1 to iNOS ratio, as well as CD163 and CD206 upregulation in the M1 macrophages, which were initially triggered by lipopolysaccharide and interferon-y.M.-A.S. acknowledges financial support from Academy of Finland (Decision no. 317316), Iran’s National Elites Foundation and Iran Nanotechnology Initiative Council. T.B.-R. acknowledges financial support from the Fundação para a Ciência e a Tecnologia (Grant no. SFRH/BD/110859/2015). Financial support from the FEDER - Fundo Europeu de Desenvolvimento Regional funds through the COMPETE 2020 Operacional Programme for Competitiveness and Internationalisation (POCI), Portugal 2020, and by Portuguese funds through the FCT - Fundação para a Ciência e a Tecnologia/Ministério da Ciência, Tecnologia e Inovação in the framework of the project “Institute for Research and Innovation in Health Sciences” (POCI-01-0145-FEDER-007274) is acknowledged. H.A.S. acknowledges financial support from the Sigrid Jusélius Foundation (Decision no. 4704580), the Helsinki Institute of Life Science, and the Academy of Finland (Decision no. 1317042)

Peer-to-Peer Sharing of Social Media Messages on Sexual Health in a School-Based Intervention: Opportunities and Challenges Identified in the STASH Feasibility Trial

Background: There is a strong interest in the use of social media to spread positive sexual health messages through social networks of young people. However, research suggests that this potential may be limited by a reluctance to be visibly associated with sexual health content on the web or social media and by the lack of trust in the veracity of peer sources. Objective: The aim of this study was to investigate opportunities and challenges of using social media to facilitate peer-to-peer sharing of sexual health messages within the context of STASH (Sexually Transmitted Infections and Sexual Health), a secondary school-based and peer-led sexual health intervention. Methods: Following training, and as a part of their role, student-nominated peer supporters (aged 14-16 years) invited school friends to trainer-monitored, private Facebook groups. Peer supporters posted curated educational sex and relationship content within these groups. Data came from a feasibility study of the STASH intervention in 6 UK schools. To understand student experiences of the social media component, we used data from 11 semistructured paired and group interviews with peer supporters and their friends (collectively termed students; n=42, aged 14-16 years), a web-based postintervention questionnaire administered to peer supporters (n=88), and baseline and follow-up questionnaires administered to students in the intervention year group (n=680 and n=603, respectively). We carried out a thematic analysis of qualitative data and a descriptive analysis of quantitative data. Results: Message sharing by peer supporters was hindered by variable engagement with Facebook. The trainer-monitored and private Facebook groups were acceptable to student members (peer supporters and their friends) and reassuring to peer supporters but led to engagement that ran parallel to—rather than embedded in—their routine social media use. The offline context of a school-based intervention helped legitimate and augment Facebook posts; however, even where friends were receptive to STASH messages, they did not necessarily engage visibly on social media. Preferences for content design varied; however, humor, color, and text brevity were important. Preferences for social media versus offline message sharing varied. Conclusions: Invitation-only social media groups formed around peer supporters’ existing friendship networks hold potential for diffusing messages in peer-based sexual health interventions. Ideally, interactive opportunities should not be limited to single social media platforms and should run alongside offline conversations. There are tensions between offering young people autonomy to engage flexibly and authentically and the need for adult oversight of activities for information accuracy and safeguarding

Familial aggregation of early-onset cancers

This registry-linkage study evaluates familial aggregation of cancer among relatives of a population-based series of early-onset (Peer reviewe

Decoding brain basis of laughter and crying in natural scenes

Laughter and crying are universal signals of prosociality and distress, respectively. Here we investigated the functional brain basis of perceiving laughter and crying using naturalistic functional magnetic resonance imaging (fMRI) approach. We measured haemodynamic brain activity evoked by laughter and crying in three experiments with 100 subjects in each. The subjects i) viewed a 20-minute medley of short video clips, and ii) 30 min of a full-length feature film, and iii) listened to 13.5 min of a radio play that all contained bursts of laughter and crying. Intensity of laughing and crying in the videos and radio play was annotated by independent observes, and the resulting time series were used to predict hemodynamic activity to laughter and crying episodes. Multivariate pattern analysis (MVPA) was used to test for regional selectivity in laughter and crying evoked activations. Laughter induced widespread activity in ventral visual cortex and superior and middle temporal and motor cortices. Crying activated thalamus, cingulate cortex along the anterior-posterior axis, insula and orbitofrontal cortex. Both laughter and crying could be decoded accurately (66–77% depending on the experiment) from the BOLD signal, and the voxels contributing most significantly to classification were in superior temporal cortex. These results suggest that perceiving laughter and crying engage distinct neural networks, whose activity suppresses each other to manage appropriate behavioral responses to others’ bonding and distress signals

The impact of the duration of the palliative care period on cancer patients with regard to the use of hospital services and the place of death : a retrospective cohort study

Background In order to avoid unnecessary use of hospital services at the end-of-life, palliative care should be initiated early enough in order to have sufficient time to initiate and carry out good quality advance care planning (ACP). This single center study assesses the impact of the PC decision and its timing on the use of hospital services at EOL and the place of death. Methods A randomly chosen cohort of 992 cancer patients treated in a tertiary hospital between Jan 2013 -Dec 2014, who were deceased by the end of 2014, were selected from the total number of 2737 identified from the hospital database. The PC decision (the decision to terminate life-prolonging anticancer treatments and focus on symptom centered palliative care) and use of PC unit services were studied in relation to emergency department (ED) visits, hospital inpatient days and place of death. Results A PC decision was defined for 82% of the patients and 37% visited a PC unit. The earlier the PC decision was made, the more often patients had an appointment at the PC unit (> 180 days prior to death 72% and <14 days 10%). The number of ED visits and inpatient days were highest for patients with no PC decision and lowest for patients with both a PC decision and an PC unit appointment (60 days before death ED visits 1.3 vs 0.8 and inpatient days 9.9 vs 2.9 respectively, p <0.01). Patients with no PC decision died more often in secondary/tertiary hospitals (28% vs. 19% with a PC decision, and 6% with a decision and an appointment to a PC unit). Conclusions The PC decision to initiate a palliative goal for the treatment had a distinct impact on the use of hospital services at the EOL. Contact with a PC unit further increased the likelihood of EOL care at primary care.Peer reviewe

Assessing the utilization of the decision to implement a palliative goal for the treatment of cancer patients during the last year of life at Helsinki University Hospital : a historic cohort study

Background: To avoid aggressive treatments at the end-of-life and to provide palliative care (PC), physicians need to terminate futile anti-cancer treatments and define the palliative goal of the treatment in time. This single center study assesses the practices used to make the decision that leads to treatment with a palliative goal, i.e., the PC decision and its effect on anti-cancer treatments at the end of life. Material and methods: Patients with a cancer diagnosis treated in tertiary hospital during 1st January 2013 - 31st December 2014 and deceased by the end of 2014 were identified in the hospital database (N = 2737). Of these patients, 992 were randomly selected for this study. The PC decision was screened from patient records, i.e., termination of cancer-specific treatments and a focus on symptom-centered PC. Results: The PC decision was defined in 82% of the patients during the last year of life (49% >30 days and 33%Peer reviewe

Towards in cellulo virus crystallography

Viruses are a significant threat to both human health and the economy, and there is an urgent need for novel anti-viral drugs and vaccines. High-resolution viral structures inform our understanding of the virosphere, and inspire novel therapies. Here we present a method of obtaining such structural information that avoids potentially disruptive handling, by collecting diffraction data from intact infected cells. We identify a suitable combination of cell type and virus to accumulate particles in the cells, establish a suitable time point where most cells contain virus condensates and use electron microscopy to demonstrate that these are ordered crystalline arrays of empty capsids. We then use an X-ray free electron laser to provide extremely bright illumination of sub-micron intracellular condensates of bacteriophage phiX174 inside living Escherichia coli at room temperature. We have been able to collect low resolution diffraction data. Despite the limited resolution and completeness of these initial data, due to a far from optimal experimental setup, we have used novel methodology to determine a putative space group, unit cell dimensions, particle packing and likely maturation state of the particles.Peer reviewe