Clonal analysis of meningococci during a 26 year period prior to the introduction of meningococcal serogroup C vaccines

Meningococcal disease remains a public health burden in the UK and elsewhere. Invasive Neisseria meningitidis, isolated in Scotland between 1972 and 1998, were characterised retrospectively to examine the serogroup and clonal structure of the circulating population. 2607 isolates causing invasive disease were available for serogroup and MLST analysis whilst 2517 were available for multilocus sequence typing (MLST) analysis only. Serogroup distribution changed from year to year but serogroups B and C were dominant throughout. Serogroup B was dominant throughout the 1970s and early 1980s until serogroup C became dominant during the mid-1980s. The increase in serogroup C was not associated with one particular sequence type (ST) but was associated with a number of STs, including ST-8, ST-11, ST-206 and ST-334. This is in contrast to the increase in serogroup C disease seen in the 1990s that was due to expansion of the ST-11 clonal complex. While there was considerable diversity among the isolates (309 different STs among the 2607 isolates), a large proportion of isolates (59.9%) were associated with only 10 STs. These data highlight meningococcal diversity over time and the need for ongoing surveillance during the introduction of new meningococcal vaccines

It\u27s What\u27s For Lunch: Nectarines, Mushrooms, and Beef - The First Amendment and Compelled Commercial Speech

JAMES WEINSTEIN: Time for dessert, intellectual dessert. It\u27s my great pleasure to introduce and moderate a discussion between two of the nation\u27s most distinguished law professors: Kathleen Sullivan and Robert Post. Any introduction that would do justice to their accomplishments would take up far too much of the short time allotted. So, by way of a very summary and incomplete introduction, Kathleen Sullivan is the Stanley Morrison Professor of Law at Stanford Law School where she served as dean from 1999 to 2004. She is the author of numerous works on various aspects of constitutional law, including, with the late Gerald Gunther, co-author of the leading constitutional case book. Robert Post is the David Boies Professor of Law at Yale Law School and also the author of numerous works on constitutional law, including Constitutional Domains, an extremely influential book on free speech. Despite their wide-ranging interests and accomplishments in other areas of constitutional law, I think it\u27s fair to say that they both have written most extensively on and have a special interest in free speech. Both have written important articles on commercial speech, including, as it turns out, in The Supreme Court Review. And, Robert Post\u27s recent article in that publication is on the subject of today\u27s presentation, compelled commercial speech

Knots and Links in Three-Dimensional Flows

The closed orbits of three-dimensional flows form knots and links. This book develops the tools - template theory and symbolic dynamics - needed for studying knotted orbits. This theory is applied to the problems of understanding local and global bifurcations, as well as the embedding data of orbits in Morse-smale, Smale, and integrable Hamiltonian flows. The necesssary background theory is sketched; however, some familiarity with low-dimensional topology and differential equations is assumed

Developing and Diagnosing Climate Change Indicators of Regional Aerosol Optical Properties

Given the importance of aerosol particles to radiative transfer via aerosol-radiation interactions, a methodology for tracking and diagnosing causes of temporal changes in regional-scale aerosol populations is illustrated. The aerosol optical properties tracked include estimates of total columnar burden (aerosol optical depth, AOD), dominant size mode (ngstrm exponent, AE), and relative magnitude of radiation scattering versus absorption (single scattering albedo, SSA), along with metrics of the structure of the spatial field of these properties. Over well-defined regions of North America, there are generally negative temporal trends in mean and extreme AOD, and SSA. These are consistent with lower aerosol burdens and transition towards a relatively absorbing aerosol, driven primarily by declining sulfur dioxide emissions. Conversely, more remote regions are characterized by increasing mean and extreme AOD that is attributed to increased local wildfire emissions and long-range (transcontinental) transport. Regional and national reductions in anthropogenic emissions of aerosol precursors are leading to declining spatial autocorrelation in the aerosol fields and increased importance of local anthropogenic emissions in dictating aerosol burdens. However, synoptic types associated with high aerosol burdens are intensifying (becoming more warm and humid), and thus changes in synoptic meteorology may be offsetting aerosol burden reductions associated with emissions legislation

Book Reviews

Book Reviews by Charles S. Desmond, Godfrey P. Schmidt, Robert E. Sullivan, Louis C. Kaplan, and Paul C. Bartholomew

A mouse model of autism implicates endosome pH in the regulation of presynaptic calcium entry.

Psychoactive compounds such as chloroquine and amphetamine act by dissipating the pH gradient across intracellular membranes, but the physiological mechanisms that normally regulate organelle pH remain poorly understood. Interestingly, recent human genetic studies have implicated the endosomal Na+/H+ exchanger NHE9 in both autism spectrum disorders (ASD) and attention deficit hyperactivity disorder (ADHD). Plasma membrane NHEs regulate cytosolic pH, but the role of intracellular isoforms has remained unclear. We now find that inactivation of NHE9 in mice reproduces behavioral features of ASD including impaired social interaction, repetitive behaviors, and altered sensory processing. Physiological characterization reveals hyperacidic endosomes, a cell-autonomous defect in glutamate receptor expression and impaired neurotransmitter release due to a defect in presynaptic Ca2+ entry. Acute inhibition of synaptic vesicle acidification rescues release but without affecting the primary defect due to loss of NHE9

Why Major Programs Need Innovation Support Labs: An Example from the Space Shuttle Launch Program at KSC

For over 30 years the Kennedy Space Center (KSC) has processed the Space Shuttle; handling all hands-on aspects from receiving the Orbiter, External Tanks, Solid Rocket Booster Segments, and Payloads, through certification, check-out, and assembly, and ending with fueling, count-down, and launch. A team of thousands have worked this highly complicated, yet supremely organized, process and have, as a consequence, generated an exceptional amount of technology to solve a host of problems. This paper describes the contributions of one team that formed with the express purpose to help solve some of these diverse Shuttle ground processing problems