Qualitative in-depth interviews: Studying religious meaning-making in MMOs

In this chapter, Stef Aupers, Julian Schaap, and Lars de Wildt argue that a “game-centered” orient

Ontogeny of midazolam glucuronidation in preterm infants

Purpose: In preterm infants, the biotransformation of midazolam (M) to 1-OH-midazolam (OHM) by cytochrome P450 3A4 (CYP3A4) is developmentally immature, but it is currently unknown whether the glucuronidation of OHM to 1-OH-midazolam glucuronide (OHMG) is also decreased. The aim of our study was to investigate the urinary excretion of midazolam and its metabolites OHM and OHMG in preterm neonates following the intravenous (IV) or oral (PO) administration of a single M dose. Methods: Preterm infants (post-natal age 3-13 days, gestational age 26-34 4/7 weeks) scheduled to undergo a stressful procedure received a 30-min IV infusion (n=15) or a PO bolus dose (n=7) of 0.1 mg/kg midazolam. The percentage of midazolam dose excreted in the urine as M, OHM and OHMG up to 6 h post-dose was determined. Results: The median percentage of the midazolam dose excreted as M, OHM and OHMG in the urine during the 6-h interval after the IV infusion was 0.44% (range 0.02-1.39%), 0.04% (0.01-0.13%) and 1.57% (0.36-7.7%), respectively. After administration of the PO bolus dose, the median percentage of M, OHM and OHMG excreted in the urine was 0.11% (0.02-0.59%), 0.02% (0.00-0.10%) and 1.69% (0.58-7.31%), respectively. The proportion of the IV midazolam dose excreted as OHMG increased significantly with postconceptional age (r=0.73, p <0.05). Conclusion: The glucuronidation of OHM appears immature in preterm infants less than 2 weeks of age. The observed increase in urinary excretion of OHMG with postconceptional age likely reflects the combined maturation of glucuronidation and renal function

Microdosing and other phase 0 clinical trials: facilitating translation in Drug Development

Increasing costs of drug development and ethical concernsabout the risks of exposing humans and animals to novelchemical entities favor limited exposure clinical trials suchas microdosing and other phase 0 trials. An increasing bodyof research supports the validity of extrapolation from thelimited drug exposure of phase 0 approaches to the full,therapeutic exposure. An increasing number of applicationsand design options demonstrate the versatility and exibilitythese approaches offer to drug developers

Pharmacokinetic studies in children: recommendations for practice and research.

Optimising the dosing of medicines for neonates and children remains a challenge. The importance of pharmacokinetic (PK) and pharmacodynamic (PD) research is recognised both in medicines regulation and paediatric clinical pharmacology, yet there remain barriers to undertaking high-quality PK and PD studies. While these studies are essential in understanding the dose-concentration-effect relationship and should underpin dosing recommendations, this review examines how challenges affecting the design and conduct of paediatric pharmacological studies can be overcome using targeted pharmacometric strategies. Model-based approaches confer benefits at all stages of the drug life-cycle, from identifying the first dose to be used in children, to clinical trial design, and optimising the dosing regimens of older, off-patent medications. To benefit patients, strategies to ensure that new PK, PD and trial data are incorporated into evidence-based dosing recommendations are needed. This review summarises practical strategies to address current challenges, particularly the use of model-based (pharmacometric) approaches in study design and analysis. Recommendations for practice and directions for future paediatric pharmacological research are given, based on current literature and our joint international experience. Success of PK research in children requires a robust infrastructure, with sustainable funding mechanisms at its core, supported by political and regulatory initiatives, and international collaborations. There is a unique opportunity to advance paediatric medicines research at an unprecedented pace, bringing the age of evidence-based paediatric pharmacotherapy into sight

Pharmacokinetics, Pharmacodynamics, and Immunogenicity of Infliximab in Pediatric Inflammatory Bowel Disease: A Systematic Review and Revised Dosing Considerations

OBJECTIVES: Infliximab (IFX), a monoclonal antibody directed against tumor necrosis factor alpha is a potent treatment option for inflammatory bowel disease (IBD). Dosing regimens in children are extrapolated from adult data using a fixed, weight-based dose, which i

The status of paediatric medicines initiatives around the world-what has happened and what has not?

Purpose: This review was conducted to examine the current status of paediatric medicines initiatives across the globe. Methods: The authors made a non-systematic descriptive review of current world situation. Results: Two regions, the United States (US) and the European Union (EU), and the World Health Organization (WHO) have introduced strong paediatric initiatives to improve children's health through improving access to better paediatric medicines. The experience from the US initiative indicates that it is possible to stimulate development and study of paediatric medicines and provide important new information for improvement of paediatric therapy. The early results from the EU initiative are similarly encouraging. In Canada, Japan, Australia and other developed countries, specific paediatric medicines initiatives have been less extensive and weaker, with modest results. Disappointingly, current evidence suggests that results from clinical trials outside the US often do not benefit children in the country in which the trials were largely conducted. Pharmaceutical companies that have derived a financial benefit commensurate with the cost of doing the paediatric trials in one country do not seem to be making the results of these trials available to all countries if there is no financial incentive to the company. The WHO campaign 'make medicines child size' has produced substantive accomplishments in building improved foundations to improve mechanisms that will enhance children's access to critical medicines in resource-limited settings. However, practically all of this work has been performed using an amalgamation of short-term funding from a variety of sources as opposed to a sustained, programmatic commitment. Conclusions: Although much still needs to be done, it's clear that with concerted efforts and appropriate resources, change is possible but slow. Retaining and fostering public and political interest in paediatric medicines is challenging, but pivotal for success.Fil: Hoppu, Kalle. Helsinki University Central Hospital; FinlandiaFil: Anabwani, Gabriel. Botswana-Baylor Children’s Clinical Centre of Excellence; BotsuanaFil: Garcia Bournissen, Facundo. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Gobierno de la Ciudad de Buenos Aires. Hospital General de Niños "Ricardo Gutiérrez"; ArgentinaFil: Gazarian, Madlen. University of New South Wales; Australia. Sydney Children’s Hospital; AustraliaFil: Kearns, Gregory L.. The Children’s Mercy Hospital; Estados Unidos. University of Missouri; Estados UnidosFil: Nakamura, Hidefumi. National Center for Child Health and Development; JapónFil: Peterson, Robert G.. University of British Columbia; CanadáFil: Sri Ranganathan, Shalini. University Of Colombo. Faculty Of Medicine; Sri LankaFil: De Wildt, Saskia N.. Sophia Children’s Hospital; Países Bajo

The formation, properties and impact of secondary organic aerosol: current and emerging issues

Secondary organic aerosol (SOA) accounts for a significant fraction of ambient tropospheric aerosol and a detailed knowledge of the formation, properties and transformation of SOA is therefore required to evaluate its impact on atmospheric processes, climate and human health. The chemical and physical processes associated with SOA formation are complex and varied, and, despite considerable progress in recent years, a quantitative and predictive understanding of SOA formation does not exist and therefore represents a major research challenge in atmospheric science. This review begins with an update on the current state of knowledge on the global SOA budget and is followed by an overview of the atmospheric degradation mechanisms for SOA precursors, gas-particle partitioning theory and the analytical techniques used to determine the chemical composition of SOA. A survey of recent laboratory, field and modeling studies is also presented. The following topical and emerging issues are highlighted and discussed in detail: molecular characterization of biogenic SOA constituents, condensed phase reactions and oligomerization, the interaction of atmospheric organic components with sulfuric acid, the chemical and photochemical processing of organics in the atmospheric aqueous phase, aerosol formation from real plant emissions, interaction of atmospheric organic components with water, thermodynamics and mixtures in atmospheric models. Finally, the major challenges ahead in laboratory, field and modeling studies of SOA are discussed and recommendations for future research directions are proposed

"We need people to collaborate together against this disease":A qualitative exploration of perceptions of dengue fever control in caregivers' of children under 5 years, in the Peruvian Amazon

BACKGROUND:Dengue Fever presents a significant and growing burden of disease to endemic countries, where children are at particular risk. Worldwide, no effective anti-viral treatment has been identified, thus vector control is key for disease prevention, particularly in Peru where no vaccine is currently available. This qualitative study aimed to explore the perceptions of dengue control in caregivers' of children under 5 years in Peru, to help direct future mosquito control programmes and strategy. METHODS:Eighteen semi-structured interviews were conducted in one health centre in Iquitos, Peru. Interviews were audio-recorded, transcribed and translated by an independent translator. Data were analysed using an inductive thematic approach. FINDINGS:Three core analytic themes were interpreted: (1) awareness of dengue and its control, (2) perceived susceptibility of children, rural riverside communities and city inhabitants, and (3) perceived responsibility of vector control. Participants were aware of dengue symptoms, transmission and larvae eradication strategies. Misconceptions about the day-time biting behaviour of the Aedes aegypti mosquito and confusion with other mosquito-borne diseases influenced preventative practice. Community-wide lack of cooperation was recognised as a key barrier. This was strengthened by attitudes that the government or health centre were responsible for dengue control and a belief that the disease cannot be prevented through individual actions. Participants felt powerless to prevent dengue due to assumed inevitability of infection and lack of faith in preventative practices. However, children and rural communities were believed to be most vulnerable. CONCLUSIONS:Perceptions of dengue control amongst caregivers to under 5's were important in shaping their likelihood to participate in preventative practices. There is a need to address the perceived lack of community cooperation through strategies creating a sense of ownership of community control and enhancing social responsibility. The belief that dengue cannot be prevented by individual actions in a community also warrants attention. Specific misconceptions about dengue should be addressed through the community health worker system and further research directed to identify the needs of certain vulnerable groups

CHROMIC AND IRON OXIDES AS FECAL MARKERS TO IDENTIFY INDIVIDUAL WHOOPING CRANES

The whooping crane (Grus americana) is listed as endangered under the IUCN Red List, the United States Endangered Species Act, and the Canadian Species at Risk Act (BirdLife International 2012, CWS and USFWS 2007). A major focus of recovery efforts for this endangered species is reintroduction to establish new populations (CWS and USFWS 2007). Captive populations are critical as a source of individuals for reintroduction efforts and also serve as insurance populations. Currently, there are a total of 157 whooping cranes held in captive breeding centers across North America, with the largest at the USGS Patuxent Wildlife Research Center (PWRC) in Laurel, Maryland. Birds produced in this facility are currently being released as part of efforts to establish the Eastern Migratory Population (EMP, Urbanek et al. 2005) and in an effort to establish a non-migratory population in Louisiana. In the past decade, PWRC has produced and released annually an average of 18 birds into the wild; however, reproductive performance of birds at this facility is lower than desired. PWRC had a 60% fertility rate for eggs laid from 2000 through 2010 (J. N. Chandler, personal communication, 2011). Furthermore, reproductive onset in this captive population appears to be delayed compared to wild populations. In wild populations, reproductive onset (production of sperm and eggs) normally occurs ~5 years of age in both males and females, ~2 years after initial pair formation occurs (Ellis et al., 1996), while some females in the EMP have laid eggs earlier than 5 years of age (Converse et al. 2011). However, PWRC females in some cases do not start to lay eggs until 7 years of age (Mirande et al. 1996). Currently, the PWRC population consists of a total of 74 whooping cranes, including 22 pairs. Six of these pairs (27%) are consistently infertile (i.e., no production of fertile eggs) and 3 other pairs (14%) have low fertility (30- 45% fertility in eggs laid), which is variable from year to year. Six pairs (27%) are recently formed and have not produced eggs, and so have unknown fertility. This leaves only 7 pairs (33%) which contribute maximally to PWRC’s chick production (J. N. Chandler, personal communication, 2011). Because of the challenges occurring within this captive colony, PWRC and Smithsonian National Zoo have initiated a joint research project to identify potential underlying causes of poor reproduction in captive whooping cranes