Drug and poison information - the Tygerberg experience

This report is based on an analysis of 6 411 consultations processed by the Tygerberg Phannacology and Toxicology Consultation Centre. Seventy-five per cent of the consultations were of a toxicological nature: 47% related to non-drug chemicals, 37% to drugs and 16% to plants and animals. Pesticides utilised in the home environment featured most pronrinently in the non-drug chemical group, while queries about paracetamol overdose topped the list in the drug group. The most frequent queries in the biological category concerned potentially poisonous plants. Twenty-five per cent of the consultations related to phannacotherapeutics.Most potentially toxic exposures to non-drug chemicals occurred in the household setting. Contrary to popular belief, few acute pesticide poisonings were encountered as a result of exposures during farnring activities. Another important finding was that there is a frustrating lack of reliable and readily available information in respect of potentially toxic ingredients contained in household and industrial preparations.The large nnmber of household exposures highlights the need for education in the safe storage and usage of non-drug chemicals. Legislation on the inclusion of basic toxicological information and warnings on labels of household and industrial non-drug chemical products should be considered. In addition, the Government should take responsibility for centralising information on all potentially toxic non-drug chemicals and make this information available to poison centres at all times. It is also imperative that more attention be given to the training of health care professionals in applied phannacokinetics and toxicology

Ionization of Infalling Gas

H-alpha emission from neutral halo clouds probes the radiation and hydrodynamic conditions in the halo. Armed with such measurements, we can explore how radiation escapes from the Galactic plane and how infalling gas can survive a trip through the halo. The Wisconsin H-Alpha Mapper (WHAM) is one of the most sensitive instruments for detecting and mapping optical emission from the ISM. Here, we present recent results exploring the ionization of two infallling high-velocity complexes. First, we report on our progress mapping H-alpha emission covering the full extent of Complex A. Intensities are faint (<100 mR; EM <0.2 pc cm^-6 but correlate on the sky and in velocity with 21-cm emission. Second, we explore the ionized component of some Anti-Center Complex clouds studied by Peek et al. (2007) that show dynamic shaping from interaction with the Galactic halo.Comment: 4 pages, 2 figures; to appear in proceedings of "The Role of Disk-Halo Interaction in Galaxy Evolution: Outflow vs Infall?" held in Espinho, Portugal during 2008 Augus

Matching Dynamics with Constraints

We study uncoordinated matching markets with additional local constraints that capture, e.g., restricted information, visibility, or externalities in markets. Each agent is a node in a fixed matching network and strives to be matched to another agent. Each agent has a complete preference list over all other agents it can be matched with. However, depending on the constraints and the current state of the game, not all possible partners are available for matching at all times. For correlated preferences, we propose and study a general class of hedonic coalition formation games that we call coalition formation games with constraints. This class includes and extends many recently studied variants of stable matching, such as locally stable matching, socially stable matching, or friendship matching. Perhaps surprisingly, we show that all these variants are encompassed in a class of "consistent" instances that always allow a polynomial improvement sequence to a stable state. In addition, we show that for consistent instances there always exists a polynomial sequence to every reachable state. Our characterization is tight in the sense that we provide exponential lower bounds when each of the requirements for consistency is violated. We also analyze matching with uncorrelated preferences, where we obtain a larger variety of results. While socially stable matching always allows a polynomial sequence to a stable state, for other classes different additional assumptions are sufficient to guarantee the same results. For the problem of reaching a given stable state, we show NP-hardness in almost all considered classes of matching games.Comment: Conference Version in WINE 201

Stellar Abundances in the Early Galaxy and Two r-Process Components

We present quantitative predictions for the abundances of r-process elements in stars formed very early in the Galactic history using a phenomenological two-component r-process model based on the I129 and Hf182 inventory in the early solar system. This model assumes that a standard mass of the ISM dilutes the debris from an individual supernova. High frequency supernova H events and low frequency supernova L events are proposed in the model with characteristics determined by the meteoritic data on I129 and Hf182. The yields in an H or L event are obtained from these characteristics and the solar r-process abundances under the assumption that the yield template for the high mass (A > 130) nuclei associated with W182 or the low mass (A < or = 130) nuclei associated with I127 is the same for both the H and L events and follows the corresponding solar r-pattern in each mass region. The abundance of Eu, not Fe, is proposed as a key guide to the age of very metal-poor stars. We predict that stars with log epsilon (Eu) = -2.98 to -2.22 were formed from an ISM contaminated most likely by a single H event within the first 10**7 yr of the Galactic history and should have an Ag/Eu abundance ratio less than the corresponding solar r-process value by a factor of at least 10. Many of the very metal-poor stars observed so far are considered here to have been formed from an ISM contaminated by many (about 10) r-process events. Stars formed from an ISM contaminated only by a pure L event would have an Ag/Eu ratio higher than the corresponding solar r-process value but would be difficult to find due to the low frequency of the L events. However, variations in the relative abundances of the low and high mass regions should be detectable in very metal-poor stars.Comment: 46 pages, 19 figures, to appear in the Schramm Memorial Volume of Physics Report

Environmental modifiers of RTS,S/AS01 malaria vaccine efficacy in Lilongwe, Malawi

Background: RTS,S/AS01 is the first vaccine against malaria to undergo pilot implementation, beginning in 2019 and vaccinating 360,000 children per year in Malawi, Ghana, and Kenya. The four-dose vaccine is given as a primary three-dose series with a fourth dose given approximately 18 months later. The efficacy of RTS,S/AS01 was variable among the 11 sites participating in the 2009-2014 phase III trial (MALARIA-055, NCT00866619), possibly due to differences in transmission intensity. However, a within-site examination of environmental factors related to transmission intensity and their impact on vaccine efficacy has yet to be conducted. Methods: We implemented the phase III RTS,S/AS01 trial at the Malawi site, which enrolled 1578 infants (6-12 weeks) and children (5-17 months) living in the Lilongwe District in Central Malawi and followed them for 3 years between 2009 and 2014. A global positioning system survey and an ecological questionnaire were conducted to collect participant household locations and characteristics, while additional data on background malaria prevalence were obtained from a concurrent Malaria Transmission Intensity (MTI) survey. Negative binomial regression models were used to assess whether the efficacy of the vaccine varied by estimated background malaria prevalence, household roof type, or amount of nearby vegetation. Results: Vaccine efficacy did not significantly vary by estimated malaria prevalence or by roof type. However, increased vegetation cover was associated with an increase in the efficacy of the three-dose primary RTS,S/AS01 series in the 18 months before the fourth dose and a decrease in the efficacy of the primary vaccine series in the second 18 months following, if the fourth dose was not given. Vegetation cover did not alter the efficacy of the fourth dose in a statistically or practically significant manner. Conclusions: Vegetation coverage in this study site might be a proxy for nearness to rivers or branching, shallow wetlands called "dambos"which could serve as breeding sites for mosquitoes. We observed statistically significant modification of the efficacy of RTS,S/AS01 by forest cover, suggesting that initial vaccine efficacy and the importance of the fourth dose varies based on ecological context. Trial registration: Efficacy of GSK Biologicals' Candidate Malaria Vaccine (257049) Against Malaria Disease Caused by P. falciparum Infection in Infants and Children in Africa. NCT00866619 prospectively registered 20 March 2009

Familial hemiplegic migraine and episodic ataxia type-2 are caused by mutations in the Ca2+ channel gene CACNL1A4

Genes for familial hemiplegic migraine (FHM) and episodic ataxia type-2 (EA-2) have been mapped to chromosome 19p13. We characterized a brain- specific P/Q-type Ca2+ channel α1-subunit gene, CACNLIA4, covering 300 kb with 47 exons. Sequencing of all exons and their surroundings revealed polymorphic variations, including a (CA)(n)-repeat (D19S1150), a (CAG)(n)- repeat in the 3'-UTR, and different types of deleterious mutations in FHM and EA-2. In FHM, we found four different missense mutations in conserved functional domains. One mutation has occurred on two different haplotypes in unrelated FHM families. In EA-2, we found two mutations disrupting the reading frame. Thus, FHM and EA-2 can be considered as allelic channelopathies. A similar etiology may be involved in common types of migraine

Case reduction and cost-effectiveness of the RTS,S/AS01 malaria vaccine alongside bed nets in Lilongwe, Malawi

Background: RTS,S/AS01, the most advanced vaccine against malaria, is now undergoing pilot implementation in Malawi, Ghana, and Kenya where an estimated 360,000 children will be vaccinated each year. In this study we evaluate RTS,S/AS01 alongside bed net use and estimate cost-effectiveness. Methods: RTS,S/AS01 phase III trial and bed net prevalence data were used to determine the effect of vaccination in the urban/periurban and rural areas of Lilongwe, Malawi. Cost data were used to calculate the cost-effectiveness of various interventions over three years. Findings: Since bed nets reduce malaria incidence and homogeneous vaccine efficacy was assumed, participants without bed nets received greater relative benefit from vaccination with RTS,S/AS01 than participants with bed nets. Similarly, since malaria incidence in rural Lilongwe is higher than in urban Lilongwe, the impact and cost-effectiveness of vaccine interventions is increased in rural areas. In rural Lilongwe, we estimated that vaccinating one child without a bed net would prevent 2·59 (1·62 to 3·38) cases of malaria over three years, corresponding to a cost of $10·08 (7·71 to 16·13) per case averted. Alternatively, vaccinating one child with a bed net would prevent 1·59 (0·87 to 2·57) cases, corresponding to$16·43 (10·16 to 30·06) per case averted. Providing RTS,S/AS01 to 30,000 children in rural Lilongwe was estimated to cost $782,400 and to prevent 58,611 (35,778 to 82,932) cases of malaria over a three-year period. Joint interventions providing both vaccination and bed nets (to those without them) were estimated to prevent additional cases of malaria and to be similarly cost-effective, compared to vaccine-only interventions. Interpretation: To maximize malaria prevention, vaccination and bed net distribution programs could be integrated. Funding: Impacts of Environment, Host Genetics and Antigen Diversity on Malaria Vaccine Efficacy (1R01AI137410-01

Diminished Expression of Corticotropin-Releasing Hormone Receptor 2 in Human Colon Cancer Promotes Tumor Growth and Epithelial-to-Mesenchymal Transition via Persistent Interleukin-6/Stat3 Signaling

Cellular mechanisms in basic and clinical gastroenterology and hepatolog