Long-term treatment of uterine fibroids with ulipristal acetate

Objective: To investigate the efficacy and safety of ulipristal acetate (UPA) for long-term treatment of symptomatic uterine fibroids.<p></p> Design: Repeated intermittent open-label UPA courses, each followed by randomized double-blind norethisterone acetate (NETA) or placebo.<p></p> Setting: European clinical gynecology centers.<p></p> Patient(s): Two hundred and nine women with symptomatic fibroids including heavy menstrual bleeding.<p></p> Intervention(s): Patients received up to four 3-month courses of UPA 10 mg daily, immediately followed by 10-day double-blind treatment with NETA (10 mg daily) or placebo.<p></p> Main Outcome Measure(s): Amenorrhea, fibroid volume, endometrial histology.<p></p> Result(s): After the first UPA course, amenorrhea occurred in 79% of women, with median onset (from treatment start) of 4 days (interquartile range, 2–6 days). Median fibroid volume change was −45% (interquartile range, −66%; −25%). Amenorrhea rates were 89%, 88%, and 90% for the 131, 119, and 107 women who received treatment courses 2, 3, and 4, respectively. Median times to amenorrhea were 2, 3, and 3 days for treatment courses 2, 3, and 4, respectively. Median fibroid volume changes from baseline were −63%, −67%, and −72% after treatment courses 2, 3, and 4, respectively. All endometrial biopsies showed benign histology without hyperplasia; NETA did not affect fibroid volume or endometrial histology.<p></p> Conclusion(s): Repeated 3-month UPA courses effectively control bleeding and shrink fibroids in patients with symptomatic fibroids

Global sensitivity analysis in hydrological modeling: Review of concepts, methods, theoretical framework, and applications

Sensitivity analysis (SA) aims to identify the key parameters that affect model performance and it plays important roles in model parameterization, calibration, optimization, and uncertainty quantification. However, the increasing complexity of hydrological models means that a large number of parameters need to be estimated. To better understand how these complex models work, efficient SA methods should be applied before the application of hydrological modeling. This study provides a comprehensive review of global SA methods in the field of hydrological modeling. The common definitions of SA and the typical categories of SA methods are described. A wide variety of global SA methods have been introduced to provide a more efficient evaluation framework for hydrological modeling. We review, analyze, and categorize research into global SA methods and their applications, with an emphasis on the research accomplished in the hydrological modeling field. The advantages and disadvantages are also discussed and summarized. An application framework and the typical practical steps involved in SA for hydrological modeling are outlined. Further discussions cover several important and often overlooked topics, including the relationship between parameter identification, uncertainty analysis, and optimization in hydrological modeling, how to deal with correlated parameters, and time-varying SA. Finally, some conclusions and guidance recommendations on SA in hydrological modeling are provided, as well as a list of important future research directions that may facilitate more robust analyses when assessing hydrological modeling performance

Virtual Reality and Anxiety Disorders Treatment: Evolution and Future Perspectives

Virtual reality (VR) is a technology that allows the simulation of different real-life situations on a tridimensional computer-generated environment where the user can interact with the environment as if he/she were the real world. VR has potential as an exposure technique for treating anxiety disorders because VR and real objects have similar characteristics, which creates the illusion that the user is immersed and engaged with objects in the real world. Regarding the efficacy of using virtual reality exposure-based therapy (VR-EBT), for more than two decades, there has been sufficient empirical evidence regarding VR-EBT for treating anxiety disorders. Finally, this chapter ends with some directions and perspectives for future VR-EBT developments and treatments protocols

Trace elements in glucometabolic disorders: an update

Many trace elements, among which metals, are indispensable for proper functioning of a myriad of biochemical reactions, more particularly as enzyme cofactors. This is particularly true for the vast set of processes involved in regulation of glucose homeostasis, being it in glucose metabolism itself or in hormonal control, especially insulin. The role and importance of trace elements such as chromium, zinc, selenium, lithium and vanadium are much less evident and subjected to chronic debate. This review updates our actual knowledge concerning these five trace elements. A careful survey of the literature shows that while theoretical postulates from some key roles of these elements had led to real hopes for therapy of insulin resistance and diabetes, the limited experience based on available data indicates that beneficial effects and use of most of them are subjected to caution, given the narrow window between safe and unsafe doses. Clear therapeutic benefit in these pathologies is presently doubtful but some data indicate that these metals may have a clinical interest in patients presenting deficiencies in individual metal levels. The same holds true for an association of some trace elements such as chromium or zinc with oral antidiabetics. However, this area is essentially unexplored in adequate clinical trials, which are worth being performed

The noise-lovers: cultures of speech and sound in second-century Rome

This chapter provides an examination of an ideal of the ‘deliberate speaker’, who aims to reflect time, thought, and study in his speech. In the Roman Empire, words became a vital tool for creating and defending in-groups, and orators and authors in both Latin and Greek alleged, by contrast, that their enemies produced babbling noise rather than articulate speech. In this chapter, the ideal of the deliberate speaker is explored through the works of two very different contemporaries: the African-born Roman orator Fronto and the Syrian Christian apologist Tatian. Despite moving in very different circles, Fronto and Tatian both express their identity and authority through an expertise in words, in strikingly similar ways. The chapter ends with a call for scholars of the Roman Empire to create categories of analysis that move across different cultural and linguistic groups. If we do not, we risk merely replicating the parochialism and insularity of our sources.Accepted manuscrip

Interpretation diagnostic test: a handbook synopsis of laboratory medicine

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