Crizotinib progression-free survival (PFS) was not significantly different between fusion variants involving breakpoints in different ROS1 introns, nor was there a significant difference in PFS between CD74-ROS1 and non-CD74-ROS1 groups of patients. Furthermore, TP53 was most frequently mutated in patients who progressed on crizotinib, and TP53 mutations were significantly associated with shorter crizotinib PFS. ROS1 mutations, including G2032R, were observed in approximately 33% of post-crizotinib samples. Collectively, we report the prevalence of ROS1 fusions in a large-scale NSCLC population and the efficacy of crizotinib in treating patients with ROS1-rearranged NSCLC.Females from the same population usually have phenotypic variation in their mating preferences. However, the effects of this within-population variation on the sexual selection acting on males are still unclear. We used individual-based models to explore how within-population variation in female preference (i.e. which male trait value is preferred) and preference strength (i.e. how strong the preference is) affects the opportunity for sexual selection (Is ) and the evolution of a sexually selected male trait. We found the highest Is values when females had high variation in preference and an open-ended preference function. The lowest Is occurred when the magnitude of variation in female preference and male trait value were the same and preference function was closed. Male trait exaggeration was higher when there was high within-population variation in preference and females had an open-ended preference function. Also, higher male trait variation was maintained by high variation in preference, but only for a closed preference function. Thus, we found that only within-population variation in female preference, not in preference strength, influences the opportunity for sexual selection and the evolution of sexually selected male traits. Moreover, we found that the shape of the preference function (i.e. open-ended or closed) and the magnitude of within-population variation in female preference compared to male trait variation also influences the Is and consequently the evolution of male traits.
Obesity and diabetes are major public health problems. Current approaches to weight loss show varying success. Complex community-based interventions work through several interconnected stages. An individual's actions in response to an intervention depend on many known and unknown factors, which vary among individuals.
To conduct a realist synthesis to identify in which context, for whom, in what circumstances, and how weight loss interventions work in obese or overweight individuals with type 2 diabetes.
A total of 49 trials identified during a systematic review were subsequently analysed using realist methodology. This iterative process involved hypothesis generation about how participants within a particular context respond to an intervention's resources producing the outcomes. We used established behaviour change theory to look for repeating themes. Theory and 'mechanisms' were tested against the literature on what is shown to be effective. Where established theory was lacking, we discussed issues dud their specific context.The cerebral collaterals play an important role in penumbral tissue sustenance after an acute ischaemic stroke. Recent studies have demonstrated the potential role of collaterals in the selection of acute ischaemic stroke patients eligible for reperfusion therapy. However, the understanding of the significance and evidence around the role of collateral status in predicting outcomes in acute ischaemic stroke patients treated with reperfusion therapy is still unclear. Moreover, the use of pre-treatment collaterals in patient selection and prognosis is relatively underappreciated in clinical settings. A focused review of the literature was performed on the various methods of collateral evaluation and the role of collateral status in acute ischaemic stroke patients receiving reperfusion therapy. We discuss the methods of evaluating pre-treatment collaterals in clinical settings. The patient selection based on collateral status as well as the prognostic and therapeutic value of collaterals in acute ischaemic stroke, in settings of intravenous thrombolysis or endovascular therapy alone, and bridge therapy, are summarized. Recommendations for future research and possible pharmacological intervention strategies aimed at collateral enhancement are also discussed. selleck compound Collaterals may play an important role in identifying acute ischaemic stroke patients who are likely to benefit from endovascular treatment in an extended time window. Future neuroscientific efforts to better improve our understanding of the role of collaterals in acute ischaemia as well as clinical studies to delineate its role in patient selection and acute stroke prognosis are warranted.
To delineate the role of gonadotropins in male androgen biosynthesis pathways.
Case-control study.
Twenty five males with congenital hypogonadotropic hypogonadism (CHH) underwent hCG/rFSH and testosterone treatment sequentially. Serum steroid hormone profiles (testosterone precursors and metabolites) on both replacement regimens were analysed, using liquid chromatography-tandem mass spectrometry (LC-MS/MS) and compared to those of healthy controls, matched by age, BMI and serum testosterone.
On testosterone replacement, serum concentrations of the classic Δ4 pathway hormones progesterone and 17-hydroxy-progesterone (17-OHP), and the marker steroid of an alternative pathway of testosterone synthesis (androstenediol) were decreased, compared to controls. Androstanediol, a marker of the backdoor pathway of dihydrotestosterone (DHT) synthesis, was increased. 17-OH-pregnenolone, androstenedione and DHEAS (Δ5 pathway), three 11-oxygenated C19 androgens (11-keto-A4, 11-keto-T and 11-keto-DHT) and the testosts with CHH, serum steroid hormone profiles resemble those of healthy men, if hCG/rFSH is used for substitution. Gonadotropins contribute to steroid hormone production along the classic Δ4 pathway and co-activate an alternative pathway of testosterone biosynthesis via androstenediol. Backdoor DHT biosynthesis, Δ5 17-OH-pregnenolone, DHEA(S) and androstenedione synthesis and 11-oxygenated C19 androgen production are activated independently of gonadotropins. The androgen replacement modality used for treatment of hypogonadal males with absent or reduced endogenous LH/FSH secretion may impact on long-term health and quality of life.selleck compound
Top comments (0)