Workshop - Amundsen Sea Embayment Tectonic and Glacial History - Programme and Abstracts

Overall Objective: Review existing data and identify priorities for future geoscience research (terrestrial, marine and airborne) in the Amundsen Sea embayment (ASE) region required to develop a better understanding of the past, present and future behaviour of this sector of the West Antarctic Ice Sheet (WAIS). Background: The ASE is the most rapidly changing sector of the WAIS and contains enough ice to raise global sea level by 1.2 m. Over the past few years considerable efforts have been made to acquire new data to improve knowledge of the geological structure, subglacial topography, continental shelf bathymetry and glacial history of this remote region. In this workshop we aim to review the current state of knowledge on the tectonic and glacial evolution of the Amundsen Sea embayment. Particular emphasis will be placed on work that will improve boundary conditions for ice sheet models (e.g. subglacial topography, shelf bathymetry, palaeotopography, heat flow and substrate types) and provide palaeo-data against which model outputs can be compared. There will also be a focus on plans and targets for future scientific drilling that will reveal the history of this sector of the WAIS and its sensitivity to major climate changes

Piliation of Invasive Streptococcus pneumoniae Isolates in the Era before Pneumococcal Conjugate Vaccine Introduction in Malawi

The pneumococcal pilus has been shown to be an important determinant of adhesion and virulence in mouse models of colonization, pneumonia, and bacteremia. A pilus is capable of inducing protective immunity, supporting its inclusion in next-generation pneumococcal protein vaccine formulations. Whether this vaccine target is common among pneumococci in sub-Saharan Africa is uncertain. To define the prevalence and genetic diversity of type I and II pili among invasive pneumococci in Malawi prior to the introduction of the 13-valent pneumococcal conjugate vaccine (PCV13) into routine childhood immunization, we examined 188 Streptococcus pneumoniae isolates collected between 2002 and 2008 (17% serotype 1). In this region of high disease burden, we found a low frequency of invasive piliated pneumococci (14%) and pilus gene sequence diversity similar to that seen previously in multiple global pneumococcal lineages. All common serotypes with pilus were covered by PCV13 and so we predict that pilus prevalence will be reduced in the Malawian pneumococcal population after PCV13 introduction

Test-Retest Reliability of Standard Deviation of Lane Position as Assessed on a PC-Based Driving Simulator

Driving is an everyday activity that is commonly affected by neurologic disorders and medical treatments. A frequently used metric for assessing driving ability is the standard deviation of lane position (SDLP), or the amount that subjects “swerve” within their driving lane. This measurement has been used with individuals under the influence of alcohol, illicit drugs, and prescribed medications in both on-road and simulator studies. Although good test-retest reliability is critical if one is to measure change in individuals over time, there is surprisingly limited data regarding the test-retest reliability of SDLP. Objective. To examine the test-retest reliability of SDLP in subjects tested at (1) a 3-month retest interval (a time frame common to clinical trials), and (2) a year or longer retest interval (a time period over which one might track changes in neurologic patients. Methods. Group 1 completed retesting an average of 84 (s.d. = 8.1) days after their initial simulator assessment. Both HIV negative (HIV-; n = 16) and positive (HIV+; n = 13) subjects were included to explore short-term reliability in control and mildly ill patient groups. All HIV+ subjects were medically asymptomatic, and unlikely to experience HIV-related changes over this interval. Two HIV+ subjects were neuropsychologically (NP) impaired. Group 2 (n = 31), a different cohort, was retested an average of 19.8 (8.3) months after baseline. All subjects completed NP evaluations at baseline and follow-up, with NP status rated on a scale of 1 (above average) to 9 (severe impairment) by a clinician blinded to simulator performance. Twelve subjects (39%) were NP impaired. In order to examine reliability in a stable neurologic cohort, all subjects were selected because they remained at the same level of NP functioning at follow-up. SDLP was assessed in both groups using an interactive PC-based driving simulator that consisted of a monitor, steering wheel, and brake/accelerator pedals. Participants were required to maintain lane position while holding a constant speed (55 mph) and responding to divided attention tasks in the corner of the monitor. Group 2 completed an existing, standardized scenario (TOPS), while Group 1 completed a newly developed driving scenario. Both simulations lasted approximately 7 minutes. Results. Combined reliability for Group 1 was .74. Test-retest reliability was .68 for the HIVand .83 for the HIV+ subjects. For Group 2, SDLP was significantly correlated with NP functioning at baseline (r = .5, p = .005) and follow-up (r = .48, p = .006), with impaired subjects evidencing a higher SDLP than NP normal subjects at both baseline (mean of 1.9 vs 1.2; p = .006) and follow-up (1.7 vs 1.1, p = .01). Combined test-retest reliability for Group 2 was .86. The NP normal group had a test-retest reliability of .74; test-retest reliability for the NP impaired group was .87. Conclusions. SDLP is a reliable measure for periods ranging from months to years when assessed in cognitively stable subjects. As such, this may serve as a useful tool in tracking the effects of neurologic disorders and pharmacologic treatments on driving abilities

The Heliophysics Feature Catalogue, a tool for the study of solar features

The behavior of filaments and prominences during the Solar Cycle is a signature of Sun's activity. It is therefore important to follow their evolution during the cycle, in order to be able to associate it with the various phases of the Solar Cycle as well as with other Solar features or events. The virtual observatory HELIO provides information that can be used for such studies, especially its Heliophysics Feature Catalogue gives a unique access to the description of various features during around one cycle. Features available are: filaments, prominences, photospheric and coronal active regions, coronal radio emission, type III radio bursts, coronal holes and sunspots. Web interfaces allow the user to query data for these features. Useful information can also be shared with other HELIO services, such as Heliophysics Event Catalogue, which provides access to dozens of tables of events such as flares, CME

Genomic identification of a novel co-trimoxazole resistance genotype and its prevalence amongst Streptococcus pneumoniae in Malawi

Objectives This study aimed to define the molecular basis of co-trimoxazole resistance in Malawian pneumococci under the dual selective pressure of widespread co-trimoxazole and sulfadoxine/pyrimethamine use. Methods We measured the trimethoprim and sulfamethoxazole MICs and analysed folA and folP nucleotide and translated amino acid sequences for 143 pneumococci isolated from carriage and invasive disease in Malawi (2002–08). Results Pneumococci were highly resistant to both trimethoprim and sulfamethoxazole (96%, 137/143). Sulfamethoxazole-resistant isolates showed a 3 or 6 bp insertion in the sulphonamide-binding site of folP. The trimethoprim-resistant isolates fell into three genotypic groups based on dihydrofolate reductase (encoded by folA) mutations: Ile-100-Leu (10%), the Ile-100-Leu substitution together with a residue 92 substitution (56%) and those with a novel uncharacterized resistance genotype (34%). The nucleotide sequence divergence and dN/dS of folA and folP remained stable from 2004 onwards. Conclusions S. pneumoniae exhibit almost universal co-trimoxazole resistance in vitro and in silico that we believe is driven by extensive co-trimoxazole and sulfadoxine/pyrimethamine use. More than one-third of pneumococci employ a novel mechanism of co-trimoxazole resistance. Resistance has now reached a point of stabilizing evolution. The use of co-trimoxazole to prevent pneumococcal infection in HIV/AIDS patients in sub-Saharan Africa should be re-evaluated

Effects of 5-HT2C, 5-HT1A receptor challenges and modafinil on the initiation and persistence of gambling behaviours

Rationale Problematic patterns of gambling are characterised by loss of control and persistent gambling often to recover losses. However, little is known about the mechanisms that mediate initial choices to begin gambling and then continue to gamble in the face of losing outcomes. Objectives These experiments first assessed gambling and loss-chasing performance under different win/lose probabilities in C57Bl/6 mice, and then investigated the effects of antagonism of 5-HT2CR with SB242084, 5-HT1AR agonism with 8-OH-DPAT and modafinil, a putative cognitive enhancer. Results As seen in humans and other species, mice demonstrated the expected patterns of behaviour as the odds for winning were altered increasing gambling and loss-chasing when winning was more likely. SB242084 decreased the likelihood to initially gamble, but had no effects on subsequent gambling choices in the face of repeated losses. In contrast, 8-OH-DPAT had no effects on choosing to gamble in the first place, but once started 8-OH-DPAT increased gambling choices in a dose-sensitive manner. Modafinil effects were different to the serotonergic drugs in both decreasing the propensity to initiate gambling and chase losses. Conclusions We present evidence for dissociable effects of systemic drug administration on different aspects of gambling behaviour. These data extend and reinforce the importance of serotonergic mechanisms in mediating discrete components of gambling behaviour. They further demonstrate the ability of modafinil to reduce gambling behaviour. Our work using a novel mouse paradigm may be of utility in modelling the complex psychological and neurobiological underpinnings of gambling problems, including the analysis of genetic and environmental factors

Qualitative impact assessment of land management interventions on ecosystem services (“QEIA”). Report-3 theme-6: carbon sequestration

This project assessed the impacts of 741 potential land management actions, suitable for agricultural land in England, on the Farming & Countryside Programme’s Environmental Objectives (and therefore Environment Act targets and climate commitments) through 53 relevant environmental and cultural service indicators. The project used a combination of expert opinion and rapid evidence reviews, which included 1000+ pages of evidence in 10 separate reports with reference to over 2400 published studies, and an Integrated Assessment comprising expert-derived qualitative impact scores. The project has ensured that ELM schemes are evidence-based, offer good value for money, and contribute to SoS priorities for farming

Early signals of vaccine driven perturbation seen in pneumococcal carriage population genomic data

BACKGROUND: Pneumococcal conjugate vaccines (PCV) have reduced pneumococcal diseases globally. Pneumococcal genomic surveys elucidate PCV effects on population structure but are rarely conducted in low-income settings despite the high disease burden. METHODS:We undertook whole genome sequencing of 660 pneumococcal isolates collected through surveys from healthy carriers two years from PCV14 introduction and one-year post-rollout in northern Malawi. We investigated changes in population structure, within-lineage serotype dynamics, serotype diversity, and frequency of antibiotic resistance (ABR) and accessory genes. RESULTS:In the under-fives, frequency and diversity of vaccine serotypes (VT) decreased significantly post-PCV but no significant changes occurred in over-fives. Clearance of VT serotypes was consistent across different genetic backgrounds (lineages). There was an increase of non-vaccine serotypes (NVT) namely 7C, 15B/C, 23A in under-fives but 28F increased in both age groups. While carriage rates have been recently shown to remain stable post-PCV due replacement serotypes, there was no change in diversity of NVTs. Additionally, frequency of intermediate-penicillin-resistant lineages decreased post-PCV. While frequency of ABR genes remained stable, other accessory genes especially those associated with MGEs and bacteriocins showed changes in frequency post-PCV. CONCLUSIONS:We demonstrate evidence of significant population restructuring post-PCV driven by decreasing frequency of vaccine serotypes and increasing frequency of few NVTs mainly in under-fives. Continued surveillance with WGS remains crucial to fully understand dynamics of the residual VTs and replacement NVT serotypes post-PCV

Recombination in Streptococcus pneumoniae Lineages Increase with Carriage Duration and Size of the Polysaccharide Capsule

Streptococcus pneumoniae causes a high burden of invasive pneumococcal disease (IPD) globally, especially in children from resource-poor settings. Like many bacteria, the pneumococcus can import DNA from other strains or even species by transformation and homologous recombination, which has allowed the pneumococcus to evade clinical interventions such as antibiotics and pneumococcal conjugate vaccines (PCVs). Pneumococci are enclosed in a complex polysaccharide capsule that determines the serotype; the capsule varies in size and is associated with properties including carriage prevalence and virulence. We determined and quantified the association between capsule and recombination events using genomic data from a diverse collection of serotypes sampled in Malawi. We determined both the amount of variation introduced by recombination relative to mutation (the relative rate) and how many individual recombination events occur per isolate (the frequency). Using univariate analyses, we found an association between both recombination measures and multiple factors associated with the capsule, including duration and prevalence of carriage. Because many capsular factors are correlated, we used multivariate analysis to correct for collinearity. Capsule size and carriage duration remained positively associated with recombination, although with a reduced P value, and this effect may be mediated through some unassayed additional property associated with larger capsules. This work describes an important impact of serotype on recombination that has been previously overlooked. While the details of how this effect is achieved remain to be determined, it may have important consequences for the serotype-specific response to vaccines and other interventions

A simple method for directional transcriptome sequencing using Illumina technology.

High-throughput sequencing of cDNA has been used to study eukaryotic transcription on a genome-wide scale to single base pair resolution. In order to compensate for the high ribonuclease activity in bacterial cells, we have devised an equivalent technique optimized for studying complete prokaryotic transcriptomes that minimizes the manipulation of the RNA sample. This new approach uses Illumina technology to sequence single-stranded (ss) cDNA, generating information on both the direction and level of transcription throughout the genome. The protocol, and associated data analysis programs, are freely available from http://www.sanger.ac.uk/Projects/Pathogens/Transcriptome/. We have successfully applied this method to the bacterial pathogens Salmonella bongori and Streptococcus pneumoniae and the yeast Schizosaccharomyces pombe. This method enables experimental validation of genetic features predicted in silico and allows the easy identification of novel transcripts throughout the genome. We also show that there is a high correlation between the level of gene expression calculated from ss-cDNA and double-stranded-cDNA sequencing, indicting that ss-cDNA sequencing is both robust and appropriate for use in quantitative studies of transcription. Hence, this simple method should prove a useful tool in aiding genome annotation and gene expression studies in both prokaryotes and eukaryotes