The impact of new signals on precise marine navigation - initial results from an experiment in Harwich Harbour

The General Lighthouse Authorities of the United Kingdom and Ireland (GLAs) are supporting a project at University College London (UCL) to study whether it is possible to meet the International Maritime Organisation’s (IMO) future requirements for port and harbour approach using future GNSS constellations, as detailed in IMO resolution A.915. This paper presents the results of a trial focusing on the accuracy, integrity, availability and continuity of port navigation, port approach, and docking. Abstract The required accuracy for docking is 0.1 m (95\%), which currently necessitates the use of Real Time Kinematic (RTK) processing. We consider the single-epoch geometry-based approach, which is robust against loss of lock and will fully benefit from the additional satellites. The trial was held at the beginning of May 2008 and saw THV Alert navigate into Harwich Harbour while satellite observation data were recorded from the vessel and from shore-based reference stations. Additional data were obtained from nearby Ordnance Survey reference stations, and two total stations were used to track the vessel’s passage to provide a truth model. Several modernised GPS satellites were tracked. The data were processed under different scenarios, using software developed at UCL, and the positioning performance analysed. Abstract Providing integrity for single-epoch RTK is particularly difficult. The identification of phase observation outliers is not possible before the integer ambiguities are resolved, but an undetected outlier could prevent successful ambiguity resolution. However, it will not always be necessary to fix every ambiguity to achieve the required precision, particularly with a multi-GNSS constellation. This paper introduces a new algorithm for partial ambiguity resolution in the presence of measurement bias that has been developed and tested at UCL.  This algorithm results in an improved ambiguity resolution success rate at the expense of computation time

Vibrational pocket modes: predictions by the embedded crystallite method and their experimental observation

Simulation studies based on the embedded crystallite method are used to predict, with no free parameters, complex dynamical behavior for a simple alkali halide defect system, Na+ in KI. Far infrared spectroscopic measurements, including uniaxial stress, confirm the predicted vibrational properties, indicating that this methodology can readily be used for complex and extended defects in ionic crystals

Transposon mutagenesis in a hyper-invasive clinical isolate of Campylobacter jejuni reveals a number of genes with potential roles in invasion

Transposon mutagenesis has been applied to a hyper-invasive clinical isolate of Campylobacter jejuni, 01/51. A random transposon mutant library was screened in an in vitro assay of invasion and 26 mutants with a significant reduction in invasion were identified. Given that the invasion potential of C. jejuni is relatively poor compared to other enteric pathogens, the use of a hyper-invasive strain was advantageous as it greatly facilitated the identification of mutants with reduced invasion. The location of the transposon insertion in 23 of these mutants has been determined; all but three of the insertions are in genes also present in the genome-sequenced strain NCTC 11168. Eight of the mutants contain transposon insertions in one region of the genome (∼14 kb), which when compared with the genome of NCTC 11168 overlaps with one of the previously reported plasticity regions and is likely to be involved in genomic variation between strains. Further characterization of one of the mutants within this region has identified a gene that might be involved in adhesion to host cells

The changing patterns of group politics in Britain

Two interpretations of ways in which group politics in Britain have presented challenges to democracy are reviewed: neo-corporatism or pluralistic stagnation and the rise of single issue interest groups. The disappearance of the first paradigm created a political space for the second to emerge. A three-phase model of group activity is developed: a phase centred around production interests, followed by the development of broadly based 'other regarding' groups, succeeded by fragmented, inner directed groups focusing on particular interests. Explanations of the decay of corporatism are reviewed. Single issue group activity has increased as party membership has declined and is facilitated by changes in traditional media and the development of the internet. Such groups can overload the policy-making process and frustrate depoliticisation. Debates about the constitution and governance have largely ignored these issues and there is need for a debate

Concussion in sport: what is known and what is new?

The aim of this article was to summarise the latest definition of concussion, signs of concussion, as well as important facts on recovery and graduated return to play, for different age groups. New technologies available to the sports physician are listed.Keywords: concussion, diagnosis, return to play, sign

Photodynamic therapy of malignant and premalignant lesions in patients with ’field cancerization‘ of the oral cavity

The management of patients with 'field cancerization' of the oral mucosa. with multicentric foci of invasion, presents a considerable problem for the head and neck surgeon. Surgical resection of synchronous or metachronous primary squamous cell carcinomas, along with adjacent premalignant lesions, is likely to be associated with considerable mutilation. Photodynamic therapy (PDT) has been shown to be of value in the treatment of superficial tumours in the upper aerodigestive tract, with excellent healing of treated areas. This study reports the use of PDT to treat 11 patients with 'field cancerization' occurring in the oral cavity. Six 'patients had multiple primary cancers and five had single primary tumours. All had associated areas of leukoplakia. Each received Photofrin 2 mg/kg 48 hours prior to photoirradiation with 50-100 J/cm2 red laser light by surface illumination. Six to eight weeks later treated areas in 10 of the 11 patients showed a complete response to PDT; one patient had areas of residual leukoplakia. Two patients developed further areas of leukoplakia or erythroplakia within 12 months but no patient has had evidence of recurrent invasive carcinoma in the treated areas. Longer term follow-up will be necessary to exclude further recurrence. It is concluded that PDT offers an effective repeatable treatment option, whether on its own or as an adjunct to local excision, for patients with 'field cancerization' of the oral cavity

Total hip arthroplasty improves pain and function but not physical activity

Background: People with hip osteoarthritis are likely to limit physical activity (PA) engagement due to pain and lack of function. Total hip arthroplasty (THA) reduces pain and improves function, potentially allowing increased PA. PA of THA patients was quantified to 12m post-operation. The hypothesis was that post-operatively levels of PA would increase. Methods: PA of 30 THA patients (67±7 years) was objectively measured pre-operatively and three and 12 months post-operation. Harris Hip Score (HHS), Oxford Hip Score (OHS) and six minute walk test (6MWT) were recorded. Mixed linear modelling was used to examine relationships of outcomes with time, baseline BMI, age, gender and baseline HHS. Results: Time was not a significant factor in predicting volume measures of PA, including sit-to-stand transitions, upright time and steps. Notably baseline BMI was a significant predictor of upright time, steps, largest number of steps in an upright bout, HHS and 6MWT. Baseline HHS helped predict longest upright bout, cadence of walking bouts >60s and OHS. The significant effect of participant as a random intercept in the model for PA outcomes suggested habituation from pre- to post-surgery. Conclusions: Volume measures of PA did not change from pre- to 12m post-surgery despite improvement in HHS, OHS and 6MWT. Baseline BMI was a more important predictor of upright activity and stepping than time. Pre- and post-operative PA promotion could be used to modify apparently habitual low levels of PA to enable full health benefits of THA to be gained

Within-host spatiotemporal dynamics of systemic Salmonella infection during and after antimicrobial treatment

$\textbf{Objectives:}$ We determined the interactions between efficacy of antibiotic treatment, pathogen growth rates and between-organ spread during systemic $\textit{Salmonella}$ infections. $\textbf{Methods:}$ We infected mice with isogenic molecularly tagged subpopulations of either a fast-growing WT or a slow-growing $\Delta$$\textit{aroC Salmonella}$ strain. We monitored viable bacterial numbers and fluctuations in the proportions of each bacterial subpopulation in spleen, liver, blood and mesenteric lymph nodes (MLNs) before, during and after the cessation of treatment with ampicillin and ciprofloxacin. $\textbf{Results:}$ Both antimicrobials induced a reduction in viable bacterial numbers in the spleen, liver and blood. This reduction was biphasic in infections with fast-growing bacteria, with a rapid initial reduction followed by a phase of lower effect. Conversely, a slow and gradual reduction of the bacterial load was seen in infections with the slow-growing strain, indicating a positive correlation between bacterial net growth rates and the efficacy of ampicillin and ciprofloxacin. The viable numbers of either bacterial strain remained constant in MLNs throughout the treatment with a relapse of the infection with WT bacteria occurring after cessation of the treatment. The frequency of each tagged bacterial subpopulation was similar in the spleen and liver, but different from that of the MLNs before, during and after treatment. $\textbf{Conclusions:}$ In $\textit{Salmonella}$ infections, bacterial growth rates correlate with treatment efficacy. MLNs are a site with a bacterial population structure different to those of the spleen and liver and where the total viable bacterial load remains largely unaffected by antimicrobials, but can resume growth after cessation of treatment.This work was supported by the Biotechnology and Biological Sciences Research Council (BBSRC) grant number BB/M000982/1 (http://www.bbsrc.ac.uk/research/grants/grants/AwardDetails.aspx?FundingReference=BB/M000982/1). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript

Quantification of the effects of antibodies on the extra- and intracellular dynamics of Salmonella enterica.

Antibodies are known to be essential in controlling Salmonella infection, but their exact role remains elusive. We recently developed an in vitro model to investigate the relative efficiency of four different human immunoglobulin G (IgG) subclasses in modulating the interaction of the bacteria with human phagocytes. Our results indicated that different IgG subclasses affect the efficacy of Salmonella uptake by human phagocytes. In this study, we aim to quantify the effects of IgG on intracellular dynamics of infection by combining distributions of bacterial numbers per phagocyte observed by fluorescence microscopy with a mathematical model that simulates the in vitro dynamics. We then use maximum likelihood to estimate the model parameters and compare them across IgG subclasses. The analysis reveals heterogeneity in the division rates of the bacteria, strongly suggesting that a subpopulation of intracellular Salmonella, while visible under the microscope, is not dividing. Clear differences in the observed distributions among the four IgG subclasses are best explained by variations in phagocytosis and intracellular dynamics. We propose and compare potential factors affecting the replication and death of bacteria within phagocytes, and we discuss these results in the light of recent findings on dormancy of Salmonella.This work was funded by grants from the Wellcome Trust and from the Medical Research Council to PM. O.R. is supported by the Royal Society through a University Research Fellowship. M.P. is supported by a studentship from the Wellcome Trust

Dual role of splenic mononuclear and polymorphonuclear cells in the outcome of ciprofloxacin treatment of Salmonella enterica infections.

OBJECTIVES: To determine the immune cell populations associated with Salmonella enterica serovar Typhimurium before and after ciprofloxacin treatment using a murine model of systemic infection. The effect of depletion of immune cells associating with Salmonella on treatment outcome was also determined. METHODS: We infected mice with a Salmonella enterica serovar Typhimurium strain expressing GFP and used multicolour flow cytometry to identify splenic immune cell populations associating with GFP-positive Salmonella before and after treatment with ciprofloxacin. This was followed by depletion of different immune cell populations using antibodies and liposomes. RESULTS: Our results identified CD11b+CD11chi/lo (dendritic cells/macrophages) and Ly6G+CD11b+ (neutrophils) leucocytes as the main host cell populations that are associated with Salmonella after ciprofloxacin treatment. We therefore proceeded to test the effects of depletion of such populations during treatment. We show that depletion of Ly6G+CD11b+ populations resulted in an increase in the number of viable bacterial cells in the spleen at the end of ciprofloxacin treatment. Conversely, treatment with clodronate liposomes during antimicrobial treatment, which depleted the CD11b+CD11chi/lo populations, resulted in lower numbers of viable bacteria in the tissues. CONCLUSIONS: Our study identified host cells where Salmonella bacteria persist during ciprofloxacin treatment and revealed a dual and opposing effect of removal of Ly6G+CD11b+ and CD11b+CD11chi/lo host cells on the efficacy of antimicrobial treatment. This suggests a dichotomy in the role of these populations in clearance/persistence of Salmonella during antimicrobial treatment