The bioavailability of oral GI147211 (GG211), a new topoisomerase I inhibitor.

Topoisomerase I inhibitors are new compounds of interest for cancer chemotherapy. We performed a study with GI147211, a new semisynthetic camptothecin analogue, to determine the absolute bioavailability of the drug given orally. Patients with a histologically confirmed diagnosis of a solid tumour refractory to standard forms of therapy were eligible for the study. GI147211 was given orally on day 1 and as a 30-min infusion daily on days 2-5. The treatment course was repeated every 3 weeks. In subsequent patient cohorts, the dose of the oral formulation was escalated from 1.5 mg m(-2) to 6.0 mg m(-2); the dose for i.v. administration was fixed at 1.2 mg m(-2). Plasma pharmacokinetics was performed on day 1 and 2 of the first course and on day 1 of the second course using a validated high-performance liquid chromatographic assay. Nineteen patients were entered into the study; one patient was not evaluable because the treatment course was stopped prematurely. Eighteen patients received a total of 47 treatment courses. The absolute bioavailability of GI147211 averaged 1.3 +/- 5.2%. Drug appeared quickly in plasma with a median Tmax at 0.5 h. Fasting or fed state had no significant influence on the bioavailability of GI147211. The terminal half-life after administration of oral GI147211 was 6.85 +/- 3.13 h, similar to the half-life after intravenous administration. The major toxicities were neutropenia and thrombocytopenia. Nadirs for neutropenia and thrombocytopenia occurred on day 8 and day 15 respectively. Other toxicities predominantly consisted of mild and infrequent nausea and vomiting, and fatigue. The oral administration of the drug is well tolerated. Oral administration of topoisomerase I inhibitor GI147211 results in a low bioavailability with relatively wide interpatient variation. The intravenous route of administration is advised for further development of this promising topoisomerase I inhibitor

Mobilizing Afghan Militias: Civil Defense Forces vs. 'Tribal Militas'

Matthew P. Dearing and Matthew C. DuPee are Research Associates with the Program for Culture & Conflict Studies at the Naval Postgraduate School.Empowering supposed "tribal militias" in Afghanistan as a means to defend areas outside of the immediate control of Afghanistan's National Security Forces (ANSF) from Taliban and other insurgent groups has become a popular option for U.S. military strategists to consider

Micronutrient powder programs : New findings and future directions for implementation science

Although the efficacy of micronutrient powder has been established, many factors affect the uptake, use, and sustained adherence. For this reason, continuous improvements in programme design and implementation are needed during initial implementation and scale up. The systematic use of strong impact pathways and various forms of practical implementation research are two of the strategies for achieving this, bearing in mind the specific needs, constraints, and timetables of implementers and policy makers

Personality Traits of Bus Drivers conducive to maintaining good student behavior

School administrators are faced with the responsibility of disciplining students for misconduct on the school bus. Some bus drivers frequently send discipline referrals to the administration, whereas others seldom do. This study attempts to identify certain personality traits of bus drivers that contribute to good student behaviors. Bus drivers from rural Missouri school districts who drove regular school routes were given the Global 5 Personality Trait Test. Building principals from these rural school districts gathered bus discipline referrals for the first semester of the 2008-2009 school year. The research design is quantitative causal-comparative in nature, while the data was collected and analyzed with the use of multiple t-tests and the Pearson r. No significant differences between the personality traits of drivers with numerous discipline referrals were found compared to the drivers with minimal bus discipline referrals

Laboratory study of the collection efficiency of submicron aerosol particles by cloud droplets – Part II: Influence of electric charges

International audienceA new In-Cloud Aerosol Scavenging Experiment (In-CASE) has been developed to measure the collection efficiency (CE) of submicron aerosol particles by cloud droplets. Droplets fall at their terminal velocity through a 1 m high chamber in a laminar flow containing aerosol particles. At the bottom of the In-CASE chamber, the droplet train is separated from the aerosol particles flow, and the droplets are collected in an impaction cup, whereas aerosol particles are deposited on a high-efficiency particulate air (HEPA) filter. The collected droplets and the filter are then analysed by fluorescence spectrometry since the aerosol particles are atomised from a sodium fluorescein salt solution (C20H10Na2O5). In-CASE fully controls all the parameters which affect the CE – the droplets and aerosol particles size distributions are monodispersed, the electric charges of droplets and aerosol particles are known and set, and the relative humidity is indirectly controlled via the chamber's temperature. This paper details the In-CASE setup and the dataset of 70 measurements obtained to study the impact of the electric charges on CE

Sociocultural Influences on Food Choices and Implications for Sustainable Healthy Diets.

BACKGROUND: The global policy discourse on sustainability and health has called for dietary transformations that require diverse, concerted actions from governments and institutions. In this article, we highlight the need to examine sociocultural influences on food practices as precursors to food policy&nbsp;decisions. DISCUSSION: Sociocultural food practices relate to ideas and materials that give rise to food choices and food patterns of a group. We begin with a discussion of how individuals experience, interpret, negotiate, and symbolize the food world around them. We examine primarily the ideational pathways, such as identity, gender, religion, and cultural prohibitions, and their influence on food practices. We then provide guiding questions, frameworks, and a brief overview of food choice values to support policy planning and design. Lastly, we explore how sociocultural change for sustainable or healthy diets is already happening through food movements, food lifestyles, and traditional&nbsp;diets.</p

Intrahousehold management and use of nutritional supplements during the hunger gap in Maradi region, Niger: A qualitative study

Background: Nutritional supplements are used for preventing and treating childhood malnutrition. While there is a growing body of evidence on product efficacy, less emphasis has been placed on how they are perceived and used at the household level. Here, we report on the intrahousehold management of three different supplements (Ready to Use Supplementary food (RUSF), medium quantity lipid-based nutrient supplements (LNS-MQ) and Super Cereal Plus (SC+)) in the region of Maradi (Niger). The main objective of this study was to describe the use, consumption and perception of the three different nutritional products at the household level. Methods: The study was conducted in the Madarounfa district in the region of Maradi (February - March 2012). Female caregivers were purposely selected from eligible households and invited to participate. Data were collected through focus group discussion and interviews and were analyzed using thematic content analysis. Results: In total, 114 caregivers participated. Three major themes were initially identified and included preparation and conservation; consumption and sharing practices as well as perception of impact. The data showed good acceptance at the household level including perceived benefits for the target children, health improvement, prevention of illness and malnutrition. Sharing and gifting at both household and community level were also reported. Conclusions: Caregivers displayed positive perceptions toward the investigated supplements. Patterns of actual management should be considered in the design, implementation, monitoring and evaluation of future programs