Epileptogenic potential of mefloquine chemoprophylaxis: a pathogenic hypothesis

<p>Abstract</p> <p>Background</p> <p>Mefloquine has historically been considered safe and well-tolerated for long-term malaria chemoprophylaxis, but prescribing it requires careful attention in order to rule out contraindications to its use. Contraindications include a history of certain neurological conditions that might increase the risk of seizure and other adverse events. The precise pathophysiological mechanism by which mefloquine might predispose those with such a history to seizure remains unclear.</p> <p>Presentation of the hypothesis</p> <p>Studies have demonstrated that mefloquine at doses consistent with chemoprophylaxis accumulates at high levels in brain tissue, which results in altered neuronal calcium homeostasis, altered gap-junction functioning, and contributes to neuronal cell death. This paper reviews the scientific evidence associating mefloquine with alterations in neuronal function, and it suggests the novel hypothesis that among those with the prevalent EPM1 mutation, inherited and mefloquine-induced impairments in neuronal physiologic safeguards might increase risk of GABAergic seizure during mefloquine chemoprophylaxis.</p> <p>Testing and implications of the hypothesis</p> <p>Consistent with case reports of tonic-clonic seizures occurring during mefloquine chemoprophylaxis among those with family histories of epilepsy, it is proposed here that a new contraindication to mefloquine use be recognized for people with EPM1 mutation and for those with a personal history of myoclonus or ataxia, or a family history of degenerative neurologic disorder consistent with EPM1. Recommendations and directions for future research are presented.</p

Finishing the euchromatic sequence of the human genome

The sequence of the human genome encodes the genetic instructions for human physiology, as well as rich information about human evolution. In 2001, the International Human Genome Sequencing Consortium reported a draft sequence of the euchromatic portion of the human genome. Since then, the international collaboration has worked to convert this draft into a genome sequence with high accuracy and nearly complete coverage. Here, we report the result of this finishing process. The current genome sequence (Build 35) contains 2.85 billion nucleotides interrupted by only 341 gaps. It covers ∼99% of the euchromatic genome and is accurate to an error rate of ∼1 event per 100,000 bases. Many of the remaining euchromatic gaps are associated with segmental duplications and will require focused work with new methods. The near-complete sequence, the first for a vertebrate, greatly improves the precision of biological analyses of the human genome including studies of gene number, birth and death. Notably, the human enome seems to encode only 20,000-25,000 protein-coding genes. The genome sequence reported here should serve as a firm foundation for biomedical research in the decades ahead

A Sculptor for Scotland: the Life and Work of Sir John Robert Steell, RSA (1804-1892)

Sir John Steell was the most eminent and respected Scottish sculptor of his generation. He set new standards of achievement during his long and prolific career, and consistently worked towards the advancement of Scottish arts. He executed many important public monument projects for Scotland and Great Britain, and sent work to India, New Zealand and the United States. He introduced fine art bronze casting to Scotland, creating the Grove Foundry in Edinburgh in 1849 to cast the Scottish National Monument to the Duke of Wellington. Designated Sculptor in Ordinary to Her Majesty for Scotland by Queen Victoria in 1838, Steell earned a deserved reputation as the finest sculptor in Scotland. Until now, there has never been a comprehensive assessment of Steell’s life and work. The thesis and accompanying catalogue raisonne examine Steell’s career by focussing upon his major monument projects, but also assess his portraiture work and activities within the Scottish Victorian art world. Steell matured as a sculptor within a nation that was maturing aesthetically. Previous generations of Scottish sculptors with talent and ambition were essentially forced by market conditions to seek their fortunes elsewhere. Steell was the first Scottish sculptor to have a major international career while remaining in Edinburgh. Steell’s success was often used as an example that Scottish sculpture had achieved parity with sculptural practice in England and Europe. The thesis examines the conditions that allowed Steell to enjoy such a huge level of success in Edinburgh, and places Steell in context with English and European counterparts. The thesis also assesses the political and social conditions in Edinburgh that allowed Steell to dominate the local market. Also addressed are Steell’s activities within the Royal Scottish Academy, and his relationship with the Board of Manufactures, which provided early patronage and assistance. In terms of patronage, projects, methods, style, genres, display and opportunities, Steell’s career offers an excellent example of the conditions under which Victorian sculpture was created. Steell sculpted the most eminent and famous Britons of hs day, and played an essential role in the commemoration of such individuals as Sir Walter Scott, Wellington, Prince Albert and Queen Victoria for Scotland. The thesis and catalogue comprehensively examine the life and art of the man known for over fifty years as Sculptor for Scotland

Access period: An investigation of independent study time in a rural secondary school

The purpose of this qualitative study was to investigate the effectiveness of access period. Access period was originally designed to offer students a chance to enhance their academic performance by accessing a number of resources such as teachers, computers, and miscellaneous library materials. The research questions that emerged from the investigation were: 1) How are students utilizing access period?, 2) How do teachers respond to students utilization of access period?, 3) How are administrators responding to what is taking place in access period?, and 4) What suggestions can be made to better facilitate an access period? There is very little research available that is directly related to the type of independent study time I\u27m referring to when I speak of access period. The issue essentially centers around the need for an appropriate schedule that facilitates the needs of all students, staff, and community. This study took place at a rural secondary school located in the Pacific Northwest. The participants were ninth through twelfth grade students. Information was gathered in various classrooms via observations of students during access period and through a variety of methodological approaches including taped interviews with a teacher and principal and surveys of both staff and students. In order to protect the participants\u27 rights to privacy and anonymity I have provided pseudonyms for all participants in this study. After collecting and organizing extensive field notes, interviews, and survey responses, various patterns emerged in the way students conceived access period. Access period lacks uniformity of expectations and organization. Students interested in using this time appropriately often encounter an environment not conducive to studying. My research revealed that there are several apparent problems with access period as it is currently being used

A study of attitudes toward distributive and procedural aspects of the grievance procedure and organizational commitment

This study had five primary objectives. First, to determine attitudes of teacher union members and principals of public schools in the state of Wisconsin toward four aspects of the grievance procedure. Second, to determine commitment levels of teachers and principals toward the school organization. Third, to determine if there is a correlation between attitudes of union members toward the grievance procedure and commitment to the school organization. Fourth to establish if perceptions of the process of the grievance procedure (procedural aspects) are more central to expressed attitude toward the grievance procedure than are perceptions of outcomes (distributive aspects). Fifth, to examine whether demographic variables have an effect on attitude toward the grievance procedure and/or organizational commitment levels. The methodology employed was a mail survey of teacher members of the Wisconsin Education Association Council (WEAC) and principals of public schools. Correlation analysis, regression procedures, and multivariate analysis of variance (MANOVA) were used to analyze the relationships between Section One means (ATGP) and Section Two means (OCQ) and the independent variables included in this study. Results indicate that teachers and principals have positive attitudes toward the grievance procedure, and have higher than average levels of commitment to their school organizations. A correlation was established between attitude toward the grievance procedure and commitment to the school organization. Analysis of the four identified aspects of the grievance procedure provided additional insight into the procedural and distributive aspects of the grievance procedure process. Teachers and principals have reversed and contrasting perceptions of the importance of these elements, that is, teachers prioritized the procedural elements, while principals prioritized the distributive elements. Analysis of demographic data also established a significant relationship between Section One means (ATGP) and gender, age, educational level, union involvement, and tenure, and between Section Two means (OCQ) and age, geographical area, union involvement, and the consensus or win-win bargaining model. The question of what shapes the level of commitment of individuals to the public sector organization is a fundamental issue in labor relations and public sector negotiations. This study has made a significant contribution toward analysis of this issue

Identification of cDNAs by direct hybridization using cosmid probes

The goal of this effort is to quickly obtain as many chromosome-specific cDNAs with as much map and sequence detail as possible. Many techniques have been proposed to isolate and identify genes within defined genomic regions; the technique discussed here is direct hybridization of a relatively complex genomic probe, an entire cosmid clone, to cDNA libraries. This method continues to be a straightforward technique with a fair number of successes