Mechanisms and management of asthma exacerbations

Copyright © 2019 by the American Thoracic Society. Acute asthma remains an important medical emergency, the most frequent cause of acute admissions in children and a major source of morbidity for adults with asthma. In all ages with asthma, the presence of exacerbations is an important defining characteristic of asthma severity. In this review, we assess the epidemiology of acute asthma, the triggers of acute exacerbations, and the mechanisms that underlie these exacerbations. We also assess current treatments that prevent exacerbations, with an emphasis on the role of type 2 airway inflammation in the context of acute exacerbations and the novel treatments that effectively target this. Finally we review current mana ement strate ies of the exacerbations themselve

Hot Jupiters in binary star systems

Radial velocity surveys find Jupiter mass planets with semi-major axes a less than 0.1 AU around ~1% of solar-type stars; counting planets with $a$ as large as 5 AU, the fraction of stars having planets reaches ~ 10% {Marcy,Butler}. An examination of the distribution of semi-major axes shows that there is a clear excess of planets with orbital periods around 3 or 4 days, corresponding to a~0.03$ AU, with a sharp cutoff at shorter periods (see Figure 1). It is believed that Jupiter mass planets form at large distances from their parent stars; some fraction then migrate in to produce the short period objects. We argue that a significant fraction of the `hot Jupiters' (a<0.1 AU) may arise in binary star systems in which the orbit of the binary is highly inclined to the orbit of the planet. Mutual torques between the two orbits drive down the minimum separation or periapse r_p between the planet and its host star (the Kozai mechanism). This periapse collapse is halted when tidal friction on the planet circularizes the orbit faster than Kozai torque can excite it. The same friction then circularizes the planet orbit, producing hot Jupiters with the peak of the semimajor axis distribution lying around 3 days. For the observed distributions of binary separation, eccentricity and mass ratio, roughly 2.5% of planets with initial semimajor axis a_p ~ 5au will migrate to within 0.1au of their parent star. Kozai migration could account for 10% or more of the observed hot Jupiters.Comment: accepted to ApJ main journal, added one figure and expanded discussion

Experimental designs for identifying causal mechanisms

Experimentation is a powerful methodology that enables scientists to establish causal claims empirically. However, one important criticism is that experiments merely provide a black box view of causality and fail to identify causal mechanisms. Specifically, critics argue that, although experiments can identify average causal effects, they cannot explain the process through which such effects come about. If true, this represents a serious limitation of experimentation, especially for social and medical science research that strives to identify causal mechanisms. We consider several experimental designs that help to identify average natural indirect effects. Some of these designs require the perfect manipulation of an intermediate variable, whereas others can be used even when only imperfect manipulation is possible. We use recent social science experiments to illustrate the key ideas that underlie each of the designs proposed.National Science Foundation (U.S.) (Grant SES-0849715)National Science Foundation (U.S.) (Grant SES-0918968

Evaluating treatment effectiveness in patient subgroups: a comparison of propensity score methods with an automated matching approach.

Propensity score (Pscore) matching and inverse probability of treatment weighting (IPTW) can remove bias due to observed confounders, if the Pscore is correctly specified. Genetic Matching (GenMatch) matches on the Pscore and individual covariates using an automated search algorithm to balance covariates. This paper compares common ways of implementing Pscore matching and IPTW, with Genmatch for balancing time-constant baseline covariates}. The methods are considered when estimates of treatment effectiveness are required for patient subgroups, and the treatment allocation process differs by subgroup. We apply these methods in a prospective cohort study that estimates the effectiveness of Drotrecogin alfa activated, for subgroups of patients with severe sepsis. In a simulation study we compare the methods when the Pscore is correctly specified, and then misspecified by ignoring the subgroup-specific treatment allocation. The simulations also consider poor overlap in baseline covariates, and different sample sizes. In the case study, GenMatch reports better covariate balance than IPTW or Pscore matching. In the simulations with correctly specified Pscores, good overlap and reasonable sample sizes, all methods report minimal bias. When the Pscore is misspecified, GenMatch reports the least imbalance and bias. With small sample sizes, IPTW is the most efficient approach, but all methods report relatively high bias of treatment effects. This study shows that overall GenMatch achieves the best covariate balance for each subgroup, and is more robust to Pscore misspecification than common alternative Pscore approaches

Thuiswedstrijd in een vreemd land : Een sociaal wetenschappelijke analyse van voetbal in eigen kring

The object of this study is to examine the processes that have lead to the establishment and significance of soccer clubs of immigrants in The Netherlands. Further, a comparison has been made between the immigrant soccer players who are involved in ethnic enclave sport and immigrant soccer players who are involved in mix sport. Specifically, we focused on the integration background of the immigrants. Data has been gathered and analyzed through qualitative and quantitative methodologies, and is complemented by dept interviews, historical analysis with informants, document analysis, participation observation and survey. The data reveals that the organizational development of immigrant soccer clubs has been taken place in three phases, namely: pre-official phase, formalizing phase and take-off phase. Further, the establishment of immigrants’ soccer clubs has been taken place in three different tracks: 1. A reconstruction of the immigrants soccer clubs and networks originated from the country of origin; 2. Intra-ethnic differentiation within existing immigrant soccer clubs in the hosting country; 3. As a matter of coloring of the existing white soccer clubs, new soccer clubs are established on basis of diversity and inter-ethnic differentiation. The foundation of immigrant soccer clubs has been influenced by clusters of factors, related to the country of origin, the host country and on club level. This research has demonstrated that the ethnic opportunity structure in the country of origin, the political opportunity structure in the country of residence, the immigrant process and the cultural and political opportunity within the existing clubs, together play a important role in shaping the differential immigrant soccer clubs and it has also demonstrated that the they differ from each other in the combination of factors that relay on the structural, cultural, interactional, institutional perspectives. Soccer clubs can be compared with an arena (De Ruijter 2000). The data exposes that immigrants as well as white soccer clubs are sensitive to maintain their own cultural identities. As a result, soccer offers an outstanding opportunity for demonstrating and safeguarding ones identity. This makes it also difficult to manage soccer clubs that are dealing with people from different cultural background within one and the same club. According to Bourdieu (1991), Elling (2000) and Verweel (2000) sport is related to class and is used to maintain class and cultural differences. According to the functionalist perspective, sport contributes to the integration of people from different cultural backgrounds, due to consensus in dominant values and norms which foster the corporate culture. According to the data, soccer clubs that, as a matter of coloring process in the direct living area, are facing the inflow of people from different cultural backgrounds, are dealing with a differentiated club culture. Immigrants’ soccer clubs contribute to the development of bonding, linking and bridging capital. The development of bonding social capital and strengthening cultural identities is in the first place an important condition for the significant meaning of their bridging social capital. Furthermore, this research shows that the immigrants who are related to ethnic enclave soccer and immigrants who are playing in mix soccer clubs, participate more or less on equal level in the labor market. They differ mainly in their social cultural integration. The first group is more oriented on its own culture and identity and maintains transnational contact without being hindered in their integration process in the Dutch society. A similar finding has been demonstrated by Verweel (2006)