Transpolar voltage and polar cap flux during the substorm cycle and steady convection events

Transpolar voltages observed during traversals of the polar cap by the Defense Meteorological Satellite Program (DMSP) F-13 spacecraft during 2001 are analyzed using the expanding-contracting polar cap model of ionospheric convection. Each of the 10,216 passes is classified by its substorm phase or as a steady convection event (SCE) by inspection of the AE indices. For all phases, we detect a contribution to the transpolar voltage by reconnection in both the dayside magnetopause and in the crosstail current sheet. Detection of the IMF influence is 97% certain during quiet intervals and >99% certain during substorm/SCE growth phases but falls to 75% in substorm expansion phases: It is only 27% during SCEs. Detection of the influence of the nightside voltage is only 19% certain during growth phases, rising during expansion phases to a peak of 96% in recovery phases: During SCEs, it is >99%. The voltage during SCEs is dominated by the nightside, not the dayside, reconnection. On average, substorm expansion phases halt the growth phase rise in polar cap flux rather than reversing it. The main destruction of the excess open flux takes place during the 6- to 10-hour interval after the recovery phase (as seen in AE) and at a rate which is relatively independent of polar cap flux because the NENL has by then retreated to the far tail. The best estimate of the voltage associated with viscous-like transfer of closed field lines into the tail is around 10 kV.

An optical study of multiple NEIAL events driven by low energy electron precipitation

Optical data are compared with EISCAT radar observations of multiple Naturally Enhanced Ion-Acoustic Line (NEIAL) events in the dayside cusp. This study uses narrow field of view cameras to observe small-scale, short-lived auroral features. Using multiple-wavelength optical observations, a direct link between NEIAL occurrences and low energy (about 100 eV) optical emissions is shown. This is consistent with the Langmuir wave decay interpretation of NEIALs being driven by streams of low-energy electrons. Modelling work connected with this study shows that, for the measured ionospheric conditions and precipitation characteristics, growth of unstable Langmuir (electron plasma) waves can occur, which decay into ion-acoustic wave modes. The link with low energy optical emissions shown here, will enable future studies of the shape, extent, lifetime, grouping and motions of NEIALs.

Climate change and coastal waterbird populations – past declines and future impacts

Considerable attention has been given to the impact of climate change on avian populations over the last decade. In this paper we examine two issues with respect to coastal bird populations in the UK: (1) is there any evidence that current populations are declining due to climate change, and (2) how might we predict the response of populations in the future? We review the cause of population decline in two species associated with saltmarsh habitats. The abundance of Common Redshank Tringa totanus breeding on saltmarsh declined by about 23% between the mid-1980s and mid-1990s, but the decline appears to have been caused by an increase in grazing pressure. The number of Twite Carduelis flavirostris wintering on the coast of East Anglia has declined dramatically over recent decades; there is evidence linking this decline with habitat loss but a causal role for climate change is unclear. These examples illustrate that climate change could be having population-level impacts now, but also show that it is dangerous to become too narrowly focused on single issues affecting coastal birds. Making predictions about how populations might respond to future climate change depends on an adequate understanding of important ecological processes at an appropriate spatial scale. We illustrate this with recent work conducted on the Icelandic population of Black-tailed Godwits Limosa limosa islandica that shows large-scale regulatory processes. Most predictive models to date have focused on local populations (single estuary or a group of neighbouring estuaries). We discuss the role such models might play in risk assessment, and the need for them to be linked to larger-scale ecological processes. We argue that future work needs to focus on spatial scale issues and on linking physical models of coastal environments with important ecological processes.

Bayesian decision procedures for dose-escalation based on evidence of undesirable events and therapeutic benefit.

In this paper, Bayesian decision procedures are developed for dose-escalation studies based on bivariate observations of undesirable events and signs of therapeutic benefit. The methods generalize earlier approaches taking into account only the undesirable outcomes. Logistic regression models are used to model the two responses, which are both assumed to take a binary form. A prior distribution for the unknown model parameters is suggested and an optional safety constraint can be included. Gain functions to be maximized are formulated in terms of accurate estimation of the limits of a therapeutic window or optimal treatment of the next cohort of subjects, although the approach could be applied to achieve any of a wide variety of objectives. The designs introduced are illustrated through simulation and retrospective implementation to a completed dose-escalation study. Copyright © 2006 John Wiley & Sons, Ltd.

Sequential genome-wide association studies for monitoring adverse events in the clinical evaluation of new drugs

Pharmacovigilance, the monitoring of adverse events (AEs), is an integral part in the clinical evaluation of a new drug. Until recently, attempts to relate the incidence of AEs to putative causes have been restricted to the evaluation of simple demographic and environmental factors. The advent of large-scale genotyping, however, provides an opportunity to look for associations between AEs and genetic markers, such as single nucleotides polymorphisms (SNPs). It is envisaged that a very large number of SNPs, possibly over 500 000, will be used in pharmacovigilance in an attempt to identify any genetic difference between patients who have experienced an AE and those who have not. We propose a sequential genome-wide association test for analysing AEs as they arise, allowing evidence-based decision-making at the earliest opportunity. This gives us the capability of quickly establishing whether there is a group of patients at high-risk of an AE based upon their DNA. Our method provides a valid test which takes account of linkage disequilibrium and allows for the sequential nature of the procedure. The method is more powerful than using a correction, such as idák, that assumes that the tests are independent. Copyright © 2006 John Wiley & Sons, Ltd.

Novel high-resolution characterization of ancient DNA reveals C > U-type base modification events as the sole cause of post mortem miscoding lesions

Ancient DNA (aDNA) research has long depended on the power of PCR to amplify trace amounts of surviving genetic material from preserved specimens. While PCR permits specific loci to be targeted and amplified, in many ways it can be intrinsically unsuited to damaged and degraded aDNA templates. PCR amplification of aDNA can produce highly-skewed distributions with significant contributions from miscoding lesion damage and non-authentic sequence artefacts. As traditional PCR-based approaches have been unable to fully resolve the molecular nature of aDNA damage over many years, we have developed a novel single primer extension (SPEX)-based approach to generate more accurate sequence information. SPEX targets selected template strands at defined loci and can generate a quantifiable redundancy of coverage; providing new insights into the molecular nature of aDNA damage and fragmentation. SPEX sequence data reveals inherent limitations in both traditional and metagenomic PCR-based approaches to aDNA, which can make current damage analyses and correct genotyping of ancient specimens problematic. In contrast to previous aDNA studies, SPEX provides strong quantitative evidence that C U-type base modifications are the sole cause of authentic endogenous damage-derived miscoding lesions. This new approach could allow ancient specimens to be genotyped with unprecedented accuracy.

Climate change and coastal waterbird populations - past declines and future impacts

Considerable attention has been given to the impact of climate change on avian populations over the last decade. In this paper we examine two issues with respect to coastal bird populations in the UK: (1) is there any evidence that current populations are declining due to climate change, and (2) how might we predict the response of populations in the future? We review the cause of population decline in two species associated with saltmarsh habitats. The abundance of Common Redshank Tringa totanus breeding on saltmarsh declined by about 23% between the mid-1980s and mid-1990s, but the decline appears to have been caused by an increase in grazing pressure. The number of Twite Carduelis flavirostris wintering on the coast of East Anglia has declined dramatically over recent decades; there is evidence linking this decline with habitat loss but a causal role for climate change is unclear. These examples illustrate that climate change could be having population-level impacts now, but also show that it is dangerous to become too narrowly focused on single issues affecting coastal birds. Making predictions about how populations might respond to future climate change depends on an adequate understanding of important ecological processes at an appropriate spatial scale. We illustrate this with recent work conducted on the Icelandic population of Black-tailed Godwits Limosa limosa islandica that shows large-scale regulatory processes. Most predictive models to date have focused on local populations (single estuary or a group of neighbouring estuaries). We discuss the role such models might play in risk assessment, and the need for them to be linked to larger-scale ecological processes. We argue that future work needs to focus on spatial scale issues and on linking physical models of coastal environments with important ecological processes.

Past, present and future mathematical models for buildings (i)

This is the first of two articles presenting a detailed review of the historical evolution of mathematical models applied in the development of building technology, including conventional buildings and intelligent buildings. After presenting the technical differences between conventional and intelligent buildings, this article reviews the existing mathematical models, the abstract levels of these models, and their links to the literature for intelligent buildings. The advantages and limitations of the applied mathematical models are identified and the models are classified in terms of their application range and goal. We then describe how the early mathematical models, mainly physical models applied to conventional buildings, have faced new challenges for the design and management of intelligent buildings and led to the use of models which offer more flexibility to better cope with various uncertainties. In contrast with the early modelling techniques, model approaches adopted in neural networks, expert systems, fuzzy logic and genetic models provide a promising method to accommodate these complications as intelligent buildings now need integrated technologies which involve solving complex, multi-objective and integrated decision problems.