临床试验进展：大数据方法在临床试验中的应用

药物研发的复杂性与日俱增,而大数据时代的到来使得临床试验的进展大大加快。本期“临床试验进展”讨论了皮肤病学新创试验中面向数据的亮点,探讨了现实采用的大数据方法,剖析了对风险导向监察的新兴方法学。此外还汇总了银屑病和特应性皮炎新疗法的临床研究报告,揭示了这些疾病的影响以及Ⅱ期和Ⅲ期研究中已经取得成功的候选药。     

Seedling light limitation does not increase across a natural productivity gradient

Aims A key idea in plant community ecology is that the identity of the limiting resource shifts from soil nutrients in low productivity sites to light in high productivity sites. This idea, and its implications for plant community structure, has been tested many times in artificial productivity gradients (fertilization studies), but whether it applies to natural productivity gradients is unclear.Methods To test whether seedling light limitation would increase across a natural productivity gradient, I conducted a cross-site field experiment in southwest Michigan, USA. At each of six old fields naturally varying in productivity, I exposed transplanted seedlings of big bluestem (Andropogon gerardii) to a light addition (tie-back) treatment that increased light availability and measured their biomass after one and two growing seasons.Important findings Seedlings responded positively to the tie-back treatment, but positive responses did not increase across the natural productivity gradient. These results suggest that although light does limit seedling establishment, the strength of light limitation does not depend on variation in productivity in natural systems. Instead, light limitation interacted with a variety of site differences to determine establishment. Although the general principle that light limitation increases with productivity is well established, these results indicate that it may not always occur in natural systems.     

Propeptide big-endothelin,N-terminal-pro brain natriuretic peptide and mortality. The Ludwigshafen risk and cardiovascular health (LURIC) study

Context: The endothelin system (Big-ET-1) is a key regulator in cardiovascular (CV) disease and congestive heart failure (CHF).

Objectives: We have examined the incremental value of Big-ET-1 in predicting total and CV mortality next to the well-established CV risk marker N-Terminal Pro-B-Type Natriuretic Peptide (NT-proBNP).

Methods: Big-ET-1 and NT-proBNP were determined in 2829 participants referred for coronary angiography (follow-up 9.9 years).

Results: Big-ET-1 is an independent predictor of total, CV mortality and death due to CHF.

Discussion: The conjunct use of Big-ET-1 and NT-proBNP improves the risk stratification of patients with intermediate to high risk of CV death and CHF.

Conclusions: Big-ET-1improves risk stratification in patients referred for coronary angiography.     

Student conceptions about energy in biological contexts

The concept of energy serves biologists as a powerful analytical model to describe phenomena that occurs in the natural world. Due to the concept’s relevance, educational standards of different countries identify energy as a core idea for the teaching and learning of biology and other science subjects. However, previous research on students’ energy understanding has mostly focused on physics contexts. This cross-sectional study extends insight to the field by providing a systematic analysis of students’ (N = 30, grades 5, 7, 9, 11) conceptions about energy in biological contexts. In order to connect the findings to previous research, the study analyses conceptions about four energy aspects that are regarded as central for understanding the concept in different disciplinary contexts, i.e. (1) energy forms/sources, (2) transfer/transformation, (3) degradation/dissipation and (4) energy conservation. The findings identify substantial changes in students’ conceptions about energy between the different grade levels, but also highlight conceptions that students consistently employed across age groups. The results are discussed in the light of previous research on students’ progressing energy understanding and the connection of their energy understanding across different disciplinary contexts. Lastly, the article provides implications for the further development of energy teaching in biological contexts.     

Female remating propensity contingent on sexual cannibalism in sagebrush crickets, Cyphoderris strepitans: a mechanism of cryptic female choice

Male sagebrush crickets (Cyphoderris strepitans) permit femalesto engage in an unusual form of sexual cannibalism during copulation:females feed on males' fleshy hind wings and ingest hemolymphoozing from the wounds they inflict. These wounds are not fatal,and normally only a portion of the hind wings are eaten at anyone mating, so that mated males are not precluded from matingagain. As a result, nonvirgin males have fewer material resources tooffer females than do virgin males, such that females shouldbe selected to preferentially mate with high-investment virginmales. We tested the hypothesis that female mating preferencesfavor males capable of supplying females with the highest materialinvestment. Our results indicate that both female diet and opportunitiesfor sexual cannibalism influence female mating behavior. Femalesmaintained on a low-nutrient diet mounted males significantlysooner than females maintained on a high-nutrient diet, indicatingthat a female's overall nutrient intake may determine her propensityto mate. In addition, females were significantly more reluctantto mount and mate with males whose hind wings had been surgicallyremoved and thus were incapable of providing females with awing meal. Finally, females initially mated to dewinged malesremated with winged males significantly sooner than femalesallowed to feed freely during their initial mating, resultingin cryptic female choice of investing males.