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Lerche Boisen posted an update 1 week, 3 days ago
Hepatic drug metabolism is a major route of drug elimination, mediated by multiple drug-metabolizing enzymes. Any changes in the rate and extent of hepatic drug metabolism can lead to altered drug efficacy or toxicity. Accumulating clinical evidence indicates that pregnancy is accompanied by changes in hepatic drug metabolism. In this article, we discuss in vitro and in vivo tools used to study the mechanisms underlying the altered drug metabolism during pregnancy, focusing on primary hepatocyte culture, transgenic animal models, and use of probe drugs to assess change in enzymatic activity. The information obtained from these studies has enabled prediction of clinical PK changes for a given drug in pregnant women. BACKGROUND Child sexual abuse is a problem of significant proportion in Australia and globally. Prevention efforts have tended to occur on an ad hoc basis and to be poorly evaluated. A measured, evidence-based public health approach to preventing child sexual abuse is necessary to enhance the prevention agenda. OBJECTIVE The objective of this paper was to engage with the work of Letourneau and colleagues about a public health approach to child sexual abuse prevention from an Australian perspective. METHODS In this commentary paper, following on from Letourneau and colleagues, policy resistance to addressing the problem of child sexual abuse and its prevention in the Australian context is explored. Promising pockets of research, policy and practice are described that indicate greater readiness and a lessening policy resistance to address child sexual abuse through a comprehensive public health approach. Finally, ideas for enhancing primary, secondary, and tertiary prevention strategies in Australia are highlighted. CONCLUSIONS The Australian child sexual abuse prevention agenda would benefit from adopting a measured public health approach involving the design, implementation, and evaluation of primary, secondary, and tertiary interventions. Early intervention strategies are particularly underdeveloped in an Australian context. Since its adoption by the United Nations in November 1989, the Convention on the Rights of the Child (CRC) has become the most universally ratified human rights treaty in history; presently only the United States has not ratified it. The CRC articulates children’s human rights and notably includes freedom from sexual abuse and exploitation. Yet thirty years after the Convention was adopted, child sexual abuse and exploitation (CSA/E) remain serious, persistent, and evolving global issues. This overview both describes the current state of research on child sexual abuse and exploitation and evaluates the CRC’s legacy in terms of State-level responses to CSA/E. Points of agreement and disagreement over what constitutes CSA/E and how widespread it is are explored. Also presented are the contexts in which CSA/E takes place, and factors associated with children’s risk of being sexually abused or exploited. Emerging issues in these areas are the internet and children’s use of it, as children may now become subject to abuse or exploitation even when physically alone. The second part of the paper addresses the CRC’s influence on States’ domestic legislation and States’ responses to CSA/E more broadly. Gaps in efforts to monitor and report on the CRC’s implementation with respect to its impact on CSA/E are described. The discussion offers guidance for future efforts to research and respond to child sexual abuse and exploitation, and in particular the ongoing need for support to survivors beyond the legal response paradigm. PURPOSE To explore variation in perceptions regarding the natural history of asymptomatic umbilical hernias, and to characterize the influence of clinical and nonclinical factors on decision-making surrounding timing of repair. METHODS This was a survey of the American Pediatric Surgical Association. Branching logic and Likert scale questions were used to explore perceptions surrounding natural history (risk of complications and likelihood of spontaneous closure), preferred age for repair, and influence of anatomic, caregiver, sociodemographic, and biological factors on operative timing. RESULTS 44% of members completed the survey (371/846). The most common age respondents would consider elective repair was 3 years (37%), although the majority preferred to wait until 4 or 5 years (54%). Most respondents estimated a less then 1% risk of complications for unrepaired defects, and much greater variability was found in the perceived likelihood of spontaneous closure over time. Decision-making surrounding operative timing was most influenced by anatomic factors (larger defects, proboscoid changes, and interval growth) and parental anxiety surrounding need for emergency surgery, cosmesis, and stigma of parental neglect. CONCLUSION Practice and perceptions surrounding management of asymptomatic umbilical hernias vary widely. More robust epidemiological data are needed to define the likelihood of spontaneous closure in the context of age and physical exam findings. CC-92480 in vitro Collaborative efforts between surgeons and referring providers are also needed to optimize management of caregiver anxiety and expectations surrounding need for surgical referral and repair. LEVEL OF EVIDENCE Level V (expert opinion). Tip-Tilt mirrors play an important role in astronomical telescopes requiring the tracking performance at the level of microradian or sub-microradian. However, the closed-loop performance suffers a lot from the low-sample rate and time delay of image sensors. Especially, this issue is under the condition of vibrations, because dynamic behaviors are complex and the models are difficult to be obtained accurately. Another challenging issue comes from the measurement of vibrations and its extraction for the closed-loop control. This paper proposes a new method based on an add-on controller of the Tip-Tilt mirror to mitigate telescope vibrations. The proposed method only uses Tip-Tilt errors from an image sensor to implement a disturbance observer, which is not being restricted by an accurate model. As a result, the closed-loop performance can be optimized by designing of a proper Q-filter. To suppress the low-frequency and high-frequency vibrations, a novel Q-filter combining a lowpass filter and a bandpass filter is proposed here.