Dwarfs on the Shoulders of Giants: Bayesian Analysis With Informative Priors in Elite Sports Research and Decision Making

While sample sizes in elite sports are necessarily small, so are the effects that may be relevant. This conundrum is complicated by an understandable reluctance of athletes to comply with extensive study requirements. In Bayesian analyses, pre-existing knowledge (e.g., from sub-elite trials) can be formally included to supplement scarce data. Moreover, some design specifics for small sample research extend to the extreme case of a single subject. This provides the basis for actionable feedback (e.g., about individual responses) thereby incentivising participation. As a proof-of-concept, we conducted a replicated cross-over trial on the effect of cold-water immersion (CWI) on sprint performance recovery in soccer players. Times for 30 m linear sprint and the initial 5 m section, respectively, were measured by light gates before and 24 h after induction of fatigue. Data were analysed by Bayesian and by standard frequentist methods. Informative priors are based on a published metaanalysis. Seven players completed the trial. Sprint performance was 4.156 ± 0.193 s for 30 m linear sprint and 0.978 ± 0.064 s for the initial 5 m section. CWI improved recovery of sprint time for the initial 5 m section (difference to control: -0.060 ± 0.060 s, p = 0.004) but not for the full 30 m sprint (0.002 ± 0.115 s, p = 0.959), with general agreement between Bayesian and frequentist interval estimates. On the individual level, relevant differences between analytical approaches were present for most players. Changes in the two performance measures are correlated (p = 0.009) with a fairly good reproducibility of individual response patterns. Bayesian analyses with informative priors may be a practicable and meaningful option particularly for very small samples and when the analytical aim is decision making (use / don't use in the specific setting) rather than generalizable inference

The Cyclophilin-Binding Agent Sanglifehrin A Is a Dendritic Cell Chemokine and Migration Inhibitor

Sanglifehrin A (SFA) is a cyclophilin-binding immunosuppressant but the immunobiology of action is poorly understood. We and others have reported that SFA inhibits IL-12 production and antigen uptake in dendritic cells (DC) and exhibits lower activity against lymphocytes. Here we show that SFA suppresses DC chemokine production and migration. Gene expression analysis and subsequent protein level confirmation revealed that SFA suppressed CCL5, CCL17, CCL19, CXCL9 and CXCL10 expression in human monocyte-derived DC (moDC). A systems biology analysis, Onto Express, confirmed that SFA interferes with chemokine-chemokine receptor gene expression with the highest impact. Direct comparison with the related agent cyclosporine A (CsA) and dexamethasone indicated that SFA uniquely suppresses moDC chemokine expression. Competitive experiments with a 100-fold molar excess of CsA and with N-Methyl-Val-4-cyclosporin, representing a nonimmunosuppressive derivative of CsA indicated chemokine suppression through a cyclophilin-A independent pathway. Functional assays confirmed reduced migration of CD4+ Tcells and moDCs to supernatant of SFA-exposed moDCs. Vice versa, SFA-exposed moDC exhibited reduced migration against CCL19. Moreover, SFA suppressed expression of the ectoenzyme CD38 that was reported to regulate DC migration and cytokine production. These results identify SFA as a DC chemokine and migration inhibitor and provide novel insight into the immunobiology of SFA

Effects of Anacetrapib in Patients with Atherosclerotic Vascular Disease

BACKGROUND: Patients with atherosclerotic vascular disease remain at high risk for cardiovascular events despite effective statin-based treatment of low-density lipoprotein (LDL) cholesterol levels. The inhibition of cholesteryl ester transfer protein (CETP) by anacetrapib reduces LDL cholesterol levels and increases high-density lipoprotein (HDL) cholesterol levels. However, trials of other CETP inhibitors have shown neutral or adverse effects on cardiovascular outcomes. METHODS: We conducted a randomized, double-blind, placebo-controlled trial involving 30,449 adults with atherosclerotic vascular disease who were receiving intensive atorvastatin therapy and who had a mean LDL cholesterol level of 61 mg per deciliter (1.58 mmol per liter), a mean non-HDL cholesterol level of 92 mg per deciliter (2.38 mmol per liter), and a mean HDL cholesterol level of 40 mg per deciliter (1.03 mmol per liter). The patients were assigned to receive either 100 mg of anacetrapib once daily (15,225 patients) or matching placebo (15,224 patients). The primary outcome was the first major coronary event, a composite of coronary death, myocardial infarction, or coronary revascularization. RESULTS: During the median follow-up period of 4.1 years, the primary outcome occurred in significantly fewer patients in the anacetrapib group than in the placebo group (1640 of 15,225 patients [10.8%] vs. 1803 of 15,224 patients [11.8%]; rate ratio, 0.91; 95% confidence interval, 0.85 to 0.97; P=0.004). The relative difference in risk was similar across multiple prespecified subgroups. At the trial midpoint, the mean level of HDL cholesterol was higher by 43 mg per deciliter (1.12 mmol per liter) in the anacetrapib group than in the placebo group (a relative difference of 104%), and the mean level of non-HDL cholesterol was lower by 17 mg per deciliter (0.44 mmol per liter), a relative difference of -18%. There were no significant between-group differences in the risk of death, cancer, or other serious adverse events. CONCLUSIONS: Among patients with atherosclerotic vascular disease who were receiving intensive statin therapy, the use of anacetrapib resulted in a lower incidence of major coronary events than the use of placebo. (Funded by Merck and others; Current Controlled Trials number, ISRCTN48678192 ; ClinicalTrials.gov number, NCT01252953 ; and EudraCT number, 2010-023467-18 .)

PROPOSTAS DE ESTRATÉGIAS DE COMUNICAÇÃO EM MARKETING PARA ATENDER AO NOVO POSICIONAMENTO DA MARCA BASE DA EMPRESA DUDALINA S/A

Este projeto teve como objetivo que estratégias de comunicação em marketing devem ser propostas à empresa DUDALINA S/A a fim de seguir o reposicionamento da marca Base? Para responder a essa questão realizou-se um estudo científico onde buscou levantar o perfil e o público-alvo referente à marca Base nas multimarcas de Blumenau – SC e na franquia da marca Base em Balneário Camboriú – SC, foi por meio de delimitação por espaço temporal, onde pesquisou-se por meio de questionários com perguntas abertas e fechadas, 36 consumidores nas multimarcas e 35 consumidores na franquia. Dessa maneira fez-se um levantamento de dados por meio de pesquisas descritivas, quantitativas e qualitativas de campo. O objetivo geral desse estudo foi propor estratégia de comunicação em marketing para a empresa DUDALINA S/A frente ao novo posicionamento da marca Base. Os dados obtidos das pesquisas com questionários de múltipla escolha foram levantados baseando-se nos resultados percentuais que cada resposta apresentou em relação à amostra total e apresentada por meio de tabelas e gráficos seguidos de análise. As pesquisas com questionários de perguntas abertas e entrevista foram analisadas e relacionadas ao contexto. De acordo com os resultados obtidos desenvolveu-se uma sugestão de um plano de ação visando melhorar a comunicação de marketing com o público-alvo da marca Base para a empresa em estudo, permitindo agregar conhecimento e estratégia. Palavras-chave: Posicionamento. Marca. Estratégias. Comunicação em Marketing

The association of end-spurt behaviour with seasonal best time in long-distance freestyle pool swimming

To analyse the association of seasonal best time, distance and different performance levels with end-spurt behaviour in one swimming season. Race results in 800 and 1500 m pool freestyle swimming in the season 2018/2019 including 14,930 races and 2650 swimmers were obtained. The end-spurt for each race was determined by means of an End-Spurt Indicator (ESI). Subsequently, ESI was used as a dependent variable and influences were analysed using a linear mixed model with fixed effects for seasonal best time, distance, and performance level amongst others. In the 800 and 1500 m races swimmers showed a mean ESI of 2.08 (95% CI: 2.02–2.13) and 3.68 (95% CI: 3.59–3.76), respectively. There was a significant association between seasonal best time and ESI, with a better seasonal best time showing a greater ESI (F = 70.5, P < .001, f2 = 0.04). A significant effect on greater ESI was also observed for longer distance (F = 1067.5, P < .001, f2 = 0.06) and higher performance level (F = 91.1, P < .001, f2 = 0.02). Elite swimmers had a mean ESI of 5.47 (95% CI: 4.91–6.03), sub-elite swimmers of 3.74 (95% CI: 3.53–3.95) and competitive swimmers of 2.41 (95% CI: 2.37–2.46). A more pronounced end-spurt is associated with seasonal best time in long-distance pool swimming, higher performance level of the swimmer and longer race distance

Poor Reliability of Measurement Instruments to Assess Acute Responses to Load in Soccer Players Irrespective of Biological Maturity Status

Purpose: To assess the short-term reliability of measurement instruments to quantify the acute psychophysiological response to load in adolescent soccer players in relation to biological maturity. Methods: Data were collected from 108 U12 to U17 soccer players on 2 consecutive weeks (pre, n = 32; at, n = 34; and post, n = 42 estimated peak height velocity). Measurements consisted of the Short Recovery and Stress Scale, a countermovement jump, assessment of leg stiffness, and a submaximal run to assess exercise heart rate and heart rate recovery. Test-retest reliability was assessed with the coefficient of variation (CV) and intraclass correlation coefficient (ICC). Results: Items of the Short Recovery and Stress Scale showed poor reliability across maturity groups (CV = 7.0%-53.5%; ICC = .28 to.79). Only few countermovement jump variables (jump height, concentric impulse, and concentric velocity) possessed good reliability. For most variables of the countermovement jump, reliability was better for the post peak height velocity group followed by at-peak height velocity and prepeak height velocity. Very high levels of reliability across maturity groups were observed for exercise heart rate (CV &lt; 1.8%; ICC &gt; .94), while heart rate recovery was more variable (CV &lt; 16.5%; ICC &gt; .48). Conclusion: Results suggest that the majority of investigated variables have poor reliability, questioning their ability to detect small, yet meaningful changes in acute responses to load in adolescent soccer players.</p

Tracking Exciton Diffusion and Exciton Annihilation in Single Nanoparticles of Conjugated Polymers by Photon Correlation Spectroscopy

A fundamental question relating to the nature of light emission and absorption in organic semiconductors is the dimension of the domain within a bulk material responsible for the interaction of light and matter. How large can a nanoparticle become to retain the quantized nature of light emission? Excitons are only a few nanometers in size, but because they diffuse in space, they probe a much larger volume than the single molecule. When excitons meet, they may decay non-radiatively by singlet–singlet or singlet–triplet annihilation (SSA or STA). Fluorescence photon statistics reveal whether single photons are emitted (photon antibunching) or arrive in randomly spaced packets (photon bunching), offering direct insight into excitonic mobility. Single multichain nanoparticles of ladder-type poly(para-phenylene) (LPPP) are examined. The effect of SSA and STA is seen in the photon antibunching and bunching, respectively, which both decrease in fidelity as the size of the nanoparticle increases. Time resolving the photon correlation measurement yields microscopic annihilation rates for SSA and STA in agreement with values obtained from bulk LPPP films. Even though triplets in LPPP are known to be highly mobile, the results show that, on the timescale of the singlet exciton lifetime, triplet diffusion is not of significance in the STA process

Centres de langues universitaires : des salles multimédias aux espaces multifonctions, Table ronde.

International audienc

Centres de langues universitaires : des salles multimédias aux espaces multifonctions, Table ronde.

International audienc

Pharmacological characterization of a new series of carbamoylguanidines reveals potent agonism at the H2R and D3R

Even today, the role of the histamine H2 receptor (H2R) in the central nervous system (CNS) is widely unknown. In previous research, many dimeric, high-affinity and subtype-selective carbamoylguanidine-type ligands such as UR-NK22 (5, pKi = 8.07) were reported as H2R agonists. However, their applicability to the study of the H2R in the CNS is compromised by their molecular and pharmacokinetic properties, such as high molecular weight and, consequently, a limited bioavailability. To address the need for more drug-like H2R agonists with high affinity, we synthesized a series of monomeric (thio)carbamoylguanidine-type ligands containing various spacers and side-chain moieties. This structural simplification resulted in potent (partial) agonists (guinea pig right atrium, [35S]GTPγS and β-arrestin2 recruitment assays) with human (h) H2R affinities in the one-digit nanomolar range (pKi (139, UR-KAT523): 8.35; pKi (157, UR-MB-69): 8.69). Most of the compounds presented here exhibited an excellent selectivity profile towards the hH2R, e.g. 157 being at least 3800-fold selective within the histamine receptor family. The structural similarities of our monomeric ligands to pramipexole (6), a dopamine receptor agonist, suggested an investigation of the binding behavior at those receptors. The target compounds were (partial) agonists with moderate affinity at the hD2longR and agonists with high affinity at the hD3R (e.g. pKi (139, UR-KAT523): 7.80; pKi (157, UR-MB-69): 8.06). In summary, we developed a series of novel, more drug-like H2R and D3R agonists for the application in recombinant systems in which either the H2R or the D3R is solely expressed. Furthermore, our ligands are promising lead compounds in the development of selective H2R agonists for future in vivo studies or experiments utilizing primary tissue to unravel the role and function of the H2R in the CNS