This article is a clinical guide which discusses the “state-of-the-art” usage of the classic monoamine oxidase inhibitor (MAOI) antidepressants (phenelzine, tranylcypromine, and isocarboxazid) in modern psychiatric practice. The guide is for all clinicians, including those who may not be experienced MAOI prescribers. It discusses indications, drug-drug interactions, side-effect management, and the safety of various augmentation strategies. There is a clear and broad consensus (more than 70 international expert endorsers), based on 6 decades of experience, for the recommendations herein exposited. They are based on empirical evidence and expert opinion—this guide is presented as a new specialist-consensus standard. The guide provides practical clinical advice, and is the basis for the rational use of these drugs, particularly because it improves and updates knowledge, and corrects the various misconceptions that have hitherto been prominent in the literature, partly due to insufficient knowledge of pharmacology. The guide suggests that MAOIs should always be considered in cases of treatment-resistant depression (including those melancholic in nature), and prior to electroconvulsive therapy—while taking into account of patient preference. In selected cases, they may be considered earlier in the treatment algorithm than has previously been customary, and should not be regarded as drugs of last resort; they may prove decisively effective when many other treatments have failed. The guide clarifies key points on the concomitant use of incorrectly proscribed drugs such as methylphenidate and some tricyclic antidepressants. It also illustrates the straightforward “bridging” methods that may be used to transition simply and safely from other antidepressants to MAOIs.

Radiocarbon (14C) ages cannot provide absolutely dated chronologies for archaeological or paleoenvironmental studies directly but must be converted to calendar age equivalents using a calibration curve compensating for fluctuations in atmospheric 14C concentration. Although calibration curves are constructed from independently dated archives, they invariably require revision as new data become available and our understanding of the Earth system improves. In this volume the international 14C calibration curves for both the Northern and Southern Hemispheres, as well as for the ocean surface layer, have been updated to include a wealth of new data and extended to 55,000 cal BP. Based on tree rings, IntCal20 now extends as a fully atmospheric record to ca. 13,900 cal BP. For the older part of the timescale, IntCal20 comprises statistically integrated evidence from floating tree-ring chronologies, lacustrine and marine sediments, speleothems, and corals. We utilized improved evaluation of the timescales and location variable 14C offsets from the atmosphere (reservoir age, dead carbon fraction) for each dataset. New statistical methods have refined the structure of the calibration curves while maintaining a robust treatment of uncertainties in the 14C ages, the calendar ages and other corrections. The inclusion of modeled marine reservoir ages derived from a three-dimensional ocean circulation model has allowed us to apply more appropriate reservoir corrections to the marine 14C data rather than the previous use of constant regional offsets from the atmosphere. Here we provide an overview of the new and revised datasets and the associated methods used for the construction of the IntCal20 curve and explore potential regional offsets for tree-ring data. We discuss the main differences with respect to the previous calibration curve, IntCal13, and some of the implications for archaeology and geosciences ranging from the recent past to the time of the extinction of the Neanderthals.

Reducing the delay of backend interconnects is critical in delivering improved performance in next generation computer chips. One option is to implement interlayer dielectric (ILD) materials with increasingly lower dielectric constant (k) values. Despite industry need, there has been a recent decrease in study and production of these materials in academia and business communities. We have generated a backbone and porogen system that allows us to control porosity from 0 to 60% volume, achieve k-values from 3.4 to 1.6, maintain high chemical stability to various wet cleans, and deliver uniquely high mechanical strength at a given porosity. Finite element modeling and experimental results demonstrate that further improvements can be achieved through control of the pore volume into an ordered network. With hopes to spur more materials development, this paper discusses some molecular design and nanoscale hierarchical principles relevant to making next generation low-k ILD materials.

The IntCal09 and Marine09 radiocarbon calibration curves have been revised utilizing newly available and updated data sets from 14C measurements on tree rings, plant macrofossils, speleothems, corals, and foraminifera. The calibration curves were derived from the data using the random walk model (RWM) used to generate IntCal09 and Marine09, which has been revised to account for additional uncertainties and error structures. The new curves were ratified at the 21st International Radiocarbon conference in July 2012 and are available as Supplemental Material at www.radiocarbon.org. The database can be accessed at http://intcal.qub.ac.uk/intcal13/.

High-quality data from appropriate archives are needed for the continuing improvement of radiocarbon calibration curves. We discuss here the basic assumptions behind 14C dating that necessitate calibration and the relative strengths and weaknesses of archives from which calibration data are obtained. We also highlight the procedures, problems, and uncertainties involved in determining atmospheric and surface ocean 14C/12C in these archives, including a discussion of the various methods used to derive an independent absolute timescale and uncertainty. The types of data required for the current IntCal database and calibration curve model are tabulated with examples.

We isolated over 650 yeasts over a three year period from the gut of a variety of beetles and characterized them on the basis of LSU rDNA sequences and morphological and metabolic traits. Of these, at least 200 were undescribed taxa, a number equivalent to almost 30% of all currently recognized yeast species. A Bayesian analysis of species discovery rates predicts further sampling of previously sampled habitats could easily produce another 100 species. The sampled habitat is, thereby, estimated to contain well over half as many more species as are currently known worldwide. The beetle gut yeasts occur in 45 independent lineages scattered across the yeast phylogenetic tree, often in clusters. The distribution suggests that the some of the yeasts diversified by a process of horizontal transmission in the habitats and subsequent specialization in association with insect hosts. Evidence of specialization comes from consistent associations over time and broad geographical ranges of certain yeast and beetle species. The discovery of high yeast diversity in a previously unexplored habitat is a first step toward investigating the basis of the interactions and their impact in relation to ecology and evolution.

Information concerning parasite genomes will be fundamental to the future directions of parasitology research in the new millennium. Already the complete sequences of numerous pathogenic bacteria are available to the scientific community. These sequences contain essential information and clues on drug targets and vaccine candidates and will eventually help to unravel the mechanisms whereby pathogens succeed in their often complex and intricate life cycles. The void between a complete genome sequence of a pathogenic organism and the tools for its control might be truly enormous but the sequence provides the essential foundation for future study. Considerable progress has been made over the last five years to transfer genome technologies to eukaryotic pathogens and it was timely for the British Society for Parasitology to consider parasite genome research at the Autumn Symposium in September 1998. The meeting provided the opportunity to consider the rapid progress being made in various parasite genome projects, bioinformatics of genome analysis (including availability and access) and the exciting possibilities for research in the post-genomic era.

Critics argue that shelf registration greatly reduces the ability of underwriters to perform adequate due diligence. This argument suggests underwriters will demand greater compensation for shelf issues compared to such traditional issues as an insurance premium for protection against potential litigation or loss of reputation caused by inadequate due diligence. Our findings suggest the presence of such a premium, that the premium is higher for firms with higher expected due diligence liabilities, and that underwriters perceive that shelf registration erodes due diligence and, subsequently, price the due diligence erosion accordingly. This pricing behavior is consistent with our findings that firms with higher expected due diligence liabilities are more likely to choose traditional registration.

1. In 1923 Eggenberger and Pólya introduced the following ‘urn scheme’ as a model for the development of a contagious phenomenon. A box contains b black and r red balls, and a ball is drawn from it at random with ‘double replacement’ (i.e. whatever ball is drawn, it is returned to the box together with a fresh ball of the same colour); the procedure is then continued indefinitely. A slightly more complicated version with m-fold replacement is sometimes discussed, but it will be sufficient for our purposes to keep m = 2 and it will be convenient further to simplify the scheme by taking b = r = 1 as the initial condition. We shall however generalise the scheme in another direction by allowing an arbitrary number k(≧2) of colours. Thus initially the box will contain k differently coloured balls and successive random drawings will be followed by double replacement as before. We write s n (a k-vector with jth component ) for the numerical composition of the box immediately after the nth replacement, so that and we observe that is a Markov process for which the state-space consists of all ordered k-ads of positive integers, the (constant) transition-probability matrix having elements determined by where Sn is the sum of the components of sn and (e(i))j = δij . We shall calculate the Martin boundary for this Markov process, and point out some applications to stochastic models for population growth.