Periodontitis and systemic diseases:A record of discussions of working group 4 of the Joint EFP/AAP Workshop on Periodontitis and Systemic Diseases

Background There has been an explosion in research into possible associations between periodontitis and various systemic diseases and conditions. Aim To review the evidence for associations between periodontitis and various systemic diseases and conditions, including chronic obstructive pulmonary disease (COPD), pneumonia, chronic kidney disease, rheumatoid arthritis, cognitive impairment, obesity, metabolic syndrome and cancer, and to document headline discussions of the state of each field. Periodontal associations with diabetes, cardiovascular disease and adverse pregnancy outcomes were not discussed by working group 4. Results Working group 4 recognized that the studies performed to date were largely cross-sectional or case-control with few prospective cohort studies and no randomized clinical trials. The best current evidence suggests that periodontitis is characterized by both infection and pro-inflammatory events, which variously manifest within the systemic diseases and disorders discussed. Diseases with at least minimal evidence of an association with periodontitis include COPD, pneumonia, chronic kidney disease, rheumatoid arthritis, cognitive impairment, obesity, metabolic syndrome and cancer. The working group agreed that there is insufficient evidence to date to infer causal relationships with the exception that organisms originating in the oral microbiome can cause lung infections. Conclusions The group was unanimous in their opinion that the reported associations do not imply causality, and establishment of causality will require new studies that fulfil the Bradford Hill or equivalent criteria. Precise and community-agreed case definitions of periodontal disease states must be implemented systematically to enable consistent and clearer interpretations of studies of the relationship to systemic diseases. The members of the working group were unanimous in their opinion that to develop data that best inform clinicians, investigators and the public, studies should focus on robust disease outcomes and avoid surrogate endpoints. It was concluded that because of the relative immaturity of the body of evidence for each of the purported relationships, the field is wide open and the gaps in knowledge are large. © 2013 European Federation of Periodontology and American Academy of Periodontology.

Community structure, diversity and spatial organization of enchytraeids in Mediterranean urban holm oak stands

There is a strong northern bias in Europe as regards enchytraeid community ecology, particularly in urban settings. We approached the enchytraeid assemblages of urban holm oak stands in Naples and Siena adopting a high intensity sampling that, for the first time in the Mediterranean climate zone, would ensure that the data collected be representative of the target populations. Structural parameters (diversity and evenness, biomass, size classes, aggregation) were compared across different spatial (regional, urban district, within habitat) and temporal scales (season and year). Species richness was found to change significantly only at regional scale; background data suggest that this may depend on the higher environmental heterogeneity occurring at Naples. Differences in size class structure were significant only on a seasonal scale and within either city separately. With one exception (Fridericia bulbosa s.s.), the patterns of spatial aggregation of the common species were fairly robust and the total range of patchiness was consistent with previous studies, despite the different sampling methodologies. The size of the sampling unit, the number of replicates per plot and the number of plots proposed in this study appear suitable to obviate the difficulties of evaluating Mediterranean enchytraeid communities.

Uncovering the challenges of managing cachexia in advanced cancer: Preliminary results from semi-structured interviews with healthcare professionals in a regional cancer centre

Background: Cancer cachexia is a complex metabolic syndrome characterised by severe and progressive weight loss which is predominantly muscle mass. It is a devastating and distressing complication of advanced cancer with profound bio-psycho-social implications for patients and their families. At present there is no curative treatment for cachexiain advanced cancer therefore the most important healthcare response entails the minimisation of the psycho-social distress associated with it. However the literature suggests healthcare professionals’are missing opportunities to intervene and respond to the multi-dimensional needs of this population.

Objective:The objective of this study was to explore healthcare professionals’ response to cachexia in advanced cancer.

Methods: An interpretative qualitative approach was adopted in this study. A purposive sample of doctors, nurses, specialist nurses and dieticians were recruited from a regional cancer centre between November 2009 and November 2010. Data was collection was twofold: two multi-professional focus groups were conducted first to uncover the main themes and issues in cachexia management. This data then informed the interview schedule for the following 25 individual semi-structured interviews.

Results: Preliminary data analysis of the semi-structured interviews revealed distinct differences between disciplines in their perceptions of cancer cachexia which influenced their response to it in clinical practice. The commonality between disciplines, with the exception of palliative care, was a reliance on the biomedical approach to cancer cachexia management.

Discussion and Conclusions: Cancer cachexia is a complex and challenging syndrome which needs to be addressed from a holistic model of care to reflect the multi-dimensional needs of this patient group. The perspectives of those involved in care delivery is required in order to inform the development of interventions aimed at minimising the distress associated with this devastating syndrome.

New insights on postglacial colonization in western Europe: the phylogeography of the Leisler’s bat (Nyctalus leisleri)

Despite recent advances in the understanding of the interplay between a dynamic physical environment and phylogeography in Europe, the origins of contemporary Irish biota remain uncertain. Current thinking is that Ireland was colonized post-glacially from southern European refugia, following the end of the last glacial maximum(LGM), some 20 000 years BP. The Leisler’s bat (Nyctalus leisleri), one of the few native Irish mammal species, is widely distributed throughout Europe but, with the exception of Ireland, is generally rare and considered vulnerable. We investigate the origins and phylogeographic relationships of Irish populations in relation to those across Europe, including the closely related species N. azoreum. We use a combination of approaches, including mitochondrial and nuclear DNA markers, in addition to approximate Bayesian computation and palaeo-climatic species distribution modelling. Molecular analyses revealed two distinct and diverse European mitochondrialDNAlineages,which probably diverged in separate glacial refugia. Awestern lineage, restricted to Ireland, Britain and the Azores, comprises Irish and British N. leisleri and N. azoreum specimens; an eastern lineage is distributed throughout mainland Europe. Palaeo-climatic projections indicate suitable habitats during the LGM, including known glacial refugia, in addition to potential novel cryptic refugia along the western fringe of Europe. These results may be applicable to populations of many species.

Utilisation of a novel ProteaseTag™ activity immunoassay for the specific measurement of neutrophil elastase in patients with Cystic Fibrosis

Neutrophil elastase (NE), a biomarker of infection and inflammation, correlates with the severity of several respiratory diseases including cystic fibrosis (CF) however, its detection and quantification in biological samples is confounded by a lack of robust methodologies. Standard assays using chromogenic or fluorogenic substrates are not specific when added to complex samples containing multiple proteolytic and hydrolytic enzymes, resulting in an over-estimation of the target protease. ELISA systems measure total protein levels which can be a mixture of latent, active and protease-inhibitor complexes. We have therefore developed a novel immunoassay (NE-Tag ELISA), incorporating an activity dependent ProteaseTag™ and a specific antibody step, which is selective and specific for the capture of active NE. The objective of this study was to clinically validate NE-Tag ELISA for the detection of active NE in sputum from CF patients. Sputum (n=45) was recovered from CF patients hospitalised for acute exacerbation. Sol was recovered and analysed for NE activity using the NE-Tag ELISA and two fluorogenic substrate-based assays [1. Suc-AAPV-AMC (Sigma) and 2. InnozymeTM Immunocapture assay (Calbiochem)]. NE activity between assays and with a range of clinical parameters was correlated.A highly significant correlation was shown between assays. NE activity (NE-Tag) further correlated appropriately with clinical parameters: inversely with FEV1 (p = 0.036) and positively with CRP (p = 0.035), neutrophils and total white cell counts (p < 0.001). The InnozymeTM assay showed similar correlations with the clinical parameters (with the exception of CRP). No correlations with any of the clinical parameters were observed when NE was measured using the standard fluorogenic substrate.

Transcriptome analysis of a parasitic clade V nematode:comparative analysis of potential molecular anthelmintic targets in Cylicostephanus goldi

Clade V nematodes comprise several parasitic species that include the cyathostomins, primary helminth pathogens of horses. Next generation transcriptome datasets are available for eight parasitic clade V nematodes, although no equine parasites are included in this group. Here, we report next generation transcriptome sequencing analysis for the common cyathostomin species, Cylicostephanus goldi. A cDNA library was generated from RNA extracted from 17 C. goldi male and female adult parasites. Following sequencing using a 454 GS FLX pyrosequencer, a total of 475,215 sequencing reads were generated, which were assembled into 26,910 contigs. Using Gene Ontology and Kyoto Encyclopedia of Genes and Genomes databases, 27% of the transcriptome was annotated. Further in-depth analysis was carried out by comparing the C. goldi dataset with the next generation transcriptomes and genomes of other clade V nematodes, with the Oesophagostomum dentatum transcriptome and the Haemonchus contortus genome showing the highest levels of sequence identity with the cyathostomin dataset (45%). The C. goldi transcriptome was mined for genes associated with anthelmintic mode of action and/or resistance. Sequences encoding proteins previously associated with the three major anthelmintic classes used in horses were identified, with the exception of the P-glycoprotein group. Targeted resequencing of the glutamate gated chloride channel α4 subunit (glc-3), one of the primary targets of the macrocyclic lactone anthelmintics, was performed for several cyathostomin species. We believe this study reports the first transcriptome dataset for an equine helminth parasite, providing the opportunity for in-depth analysis of these important parasites at the molecular level. Sequences encoding enzymes involved in key processes and genes associated with levamisole/pyrantel and macrocyclic lactone resistance, in particular the glutamate gated chloride channels, were identified. This novel data will inform cyathostomin biology and anthelmintic resistance studies in future.

GPU Acceleration of Partial Differential Equation Solvers

Differential equations are often directly solvable by analytical means only in their one dimensional version. Partial differential equations are generally not solvable by analytical means in two and three dimensions, with the exception of few special cases. In all other cases, numerical approximation methods need to be utilized. One of the most popular methods is the finite element method. The main areas of focus, here, are the Poisson heat equation and the plate bending equation. The purpose of this paper is to provide a quick walkthrough of the various approaches that the authors followed in pursuit of creating optimal solvers, accelerated with the use of graphical processing units, and comparing them in terms of accuracy and time efficiency with existing or self-made non-accelerated solvers.

The geographical structure of British bird distributions:diversity, spatial turnover and scale

1. Using data on the spatial distribution of the British avifauna, we address three basic questions about the spatial structure of assemblages: (i) Is there a relationship between species richness (alpha diversity) and spatial turnover of species (beta diversity)? (ii) Do high richness locations have fewer species in common with neighbouring areas than low richness locations?, and (iii) Are any such relationships contingent on spatial scale (resolution or quadrat area), and do they reflect the operation of a particular kind of species-area relationship (SAR)?

2. For all measures of spatial turnover, we found a negative relationship with species richness. This held across all scales, with the exception of turnover measured as beta (sim).

3. Higher richness areas were found to have more species in common with neighbouring areas.

4. The logarithmic SAR fitted better than the power SAR overall, and fitted significantly better in areas with low richness and high turnover.

5. Spatial patterns of both turnover and richness vary with scale. The finest scale richness pattern (10 km) and the coarse scale richness pattern (90 km) are statistically unrelated. The same is true of the turnover patterns.

6. With coarsening scale, locations of the most species-rich quadrats move north. This observed sensitivity of richness 'hotspot' location to spatial scale has implications for conservation biology, e.g. the location of a reserve selected on the basis of maximum richness may change considerably with reserve size or scale of analysis.

7. Average turnover measured using indices declined with coarsening scale, but the average number of species gained or lost between neighbouring quadrats was essentially scale invariant at 10-13 species, despite mean richness rising from 80 to 146 species (across an 81-fold area increase). We show that this kind of scale invariance is consistent with the logarithmic SAR.

Activism and Restraint within the UK Supreme Court

This article provides evidence for the extent to which the UK Supreme Court as a body - and Supreme Court Justices as individuals - have displayed an activist or restrained attitude to their decision-making role. Taking October 2009 as the starting point (when the UKSC came into existence) the article surveys the degree to which the Court and individual Justices have (1) departed from precedents, (2) interpreted legislation in unanticipated ways, (3) rejected the government's position on matters of social, economic or foreign policy, and (4) developed the common law. The article concludes that, while the Supreme Court as a whole remains as conservative as the Appellate Committee of the House of Lords which preceded it (with the possible exception of its approach to immigration law), there are notable differences between the attitudes of individual Justices, one or two of whom appear to be straining at the leash.

Extraordinary solute-stress tolerance contributes to the environmental tenacity of mycobacteria

Mycobacteria are associated with a number of well-characterized diseases, yet we know little about their stress-biology in natural ecosystems. This study focuses on the isolation and characterization of strains from Yellowstone-(YNP) and Glacier-National-Parks (GNP; USA), the majority of those identified were Mycobacterium parascrofulaceum, Mycobacterium avium (YNP) or Mycobacterium gordonae (GNP). Generally, their temperature windows for growth were >60°C; selected isolates grew at super-saturated concentrations of hydrophobic stressors and at levels of osmotic stress and chaotropic activity (up to 13.4 kJkg-1) similar to, or exceeding, those for the xerophilic fungus Aspergillus wentii and solvent-tolerant bacterium Pseudomonas putida. For example, mycobacteria grew down to 0.800 water-activity indicating that they are, with the sole exception of halophiles, more xerotolerant than other bacteria (or any Archaea). Furthermore, the fatty-acid composition of Mycobacterium cells grown over a range of salt concentrations changed less than that of other bacteria, indicating a high level of resilience, regardless of the stress load. Cells of M. parascrofulaceum, M. smegmatis and M. avium resisted the acute, potentially lethal challenges from extremes of pH (<1; >13), and saturated MgCl2-solutions (5 M; 212 kJ kg-1 chaotropicity). Collectively, these findings challenge the paradigm that bacteria have solute tolerances inferior to those of eukaryotes.

Bactericidal efficacy of atmospheric pressure non-thermal plasma (APNTP) against the ESKAPE pathogens

The emergence of multidrug-resistant pathogens within the clinical environment is presenting a mounting problem in hospitals worldwide. The 'ESKAPE' pathogens (Enterococcusfaecium, Staphylococcus aureus, Klebsiella pneumoniae, Acinetobacter baumannii, Pseudomonas aeruginosa and Enterobacter spp.) have been highlighted as a group of causative organisms in a majority of nosocomial infections, presenting a serious health risk due to widespread antimicrobial resistance. The stagnating pipeline of new antibiotics requires alternative approaches to the control and treatment of nosocomial infections. Atmospheric pressure nonthermal plasma (APNTP) is attracting growing interest as an alternative infection control approach within the clinical setting. This study presents a comprehensive bactericidal assessment of an in-house-designed APNTP jet both against biofilms and planktonic bacteria of the ESKAPE pathogens. Standard plate counts and the XTT metabolic assay were used to evaluate the antibacterial effect of APNTP, with both methods demonstrating comparable eradication times. APNTP exhibited rapid antimicrobial activity against all of the ESKAPE pathogens in the planktonic mode of growth and provided efficient and complete eradication of ESKAPE pathogens in the biofilm mode of growth within 360 s, with the exception of A. baumannii where a >4log reduction in biofilm viability was observed. This demonstrates its effectiveness as a bactericidal treatment against these pathogens and further highlights its potential application in the clinical environment for the control of highly antimicrobial-resistant pathogens.

Transit timing variations in WASP-10b induced by stellar activity

The hot-JupiterWASP-10bwas reported by Maciejewski et al. to showtransit timing variations (TTVs) with an amplitude of ~3.5 min. These authors proposed that the observed TTVs were caused by a 0.1M_Jup perturbing companion with an orbital period of ~5.23 d, and hence, close to the outer 5:3 mean-motion resonance with WASP-10b. To test this scenario, we present eight new transit light curves of WASP-10b obtained with the Faulkes Telescope North and the Liverpool Telescope. The new light curves, together with 22 previously published ones, were modelled with a Markov Chain Monte Carlo transit fitting code. Transit depth differences reported forWASP-10b are thought to be due to starspot-induced brightness modulation of the host star. Assuming the star is brighter at the activity minimum, we favour a small planetary radius. We find Rp = 1.039^+0.043 _-0.049R_Jup in agreement with Johnson et al. and Maciejewski et al. Recent studies find no evidence for a significant eccentricity in this system. We present consistent system parameters for a circular orbit and refine the orbital ephemeris ofWASP-10b. Our homogeneously derived transit times do not support the previous claimed TTV signal, which was strongly dependent on two previously published transits that have been incorrectly normalized. Nevertheless, a linear ephemeris is not a statistically good fit to the transit times of WASP-10b. We show that the observed transit time variations are due to spot occultation features or systematics. We discuss and exemplify the effects of occultation spot features in the measured transit times and show that despite spot occultation during egress and ingress being difficult to distinguish in the transit light curves, they have a significant effect in the measured transit times. We conclude that if we account for spot features, the transit times of WASP-10b are consistent with a linear ephemeris with the exception of one transit (epoch 143) which is a partial transit. Therefore, there is currently no evidence for the existence of a companion to WASP-10b. Our results support the lack of TTVs of hot-Jupiters reported for the Kepler sample. 

Arsenic is not stored as arsenitephytochelatin complexes in the seaweeds Fucus spiralis and Hizikia fusiforme

Environmental context Seaweeds hyperaccumulate the toxic metalloid arsenic, but seemingly achieve detoxification by transformation to arsenosugars. The edible seaweed hijiki is a notable exception because it contains high levels of toxic arsenate and arsenite. Terrestrial plants detoxify arsenic by forming arsenitephytochelatin complexes. The hypothesis that seaweeds also synthesise phytochelatins to bind arsenite as a means of detoxification before arsenosugar synthesis is tested in this investigation. Abstract Phytochelatins (PCs), generic structure [-Glu-Cys]n-Gly, are peptides synthesised by terrestrial plants to bind toxic metal(loid)s such as cadmium and arsenic. Seaweeds are arsenic hyperaccumulators, seemingly achieving detoxification via arsenosugar biosynthesis. Whether seaweeds synthesise PCs to aid detoxification during arsenic exposure is unknown. Hizikia fusiforme (hijiki) and Fucus spiralis were used as model seaweeds: the former is known for its large inorganic arsenic concentration, whereas the latter contains mainly arsenosugars. F. spiralis was exposed to 0, 1 and 10mgL ^-1 arsenate solutions for 24h, whereas hijiki was analysed fresh. All samples contained As ^III, glutathione and reduced PC ₂, identified using HPLC-ICP-MS/ES-MS. Although hijiki contained no As ^IIIPC complexes, arsenate exposed F. spiralis generated traces of numerous arsenic compounds that might be As ^IIIGS or As ^IIIPC ₂ complexes. As ^IIIPC complexes seem not to be a principal storage form for long-term arsenic storage within seaweeds. However, 40 times higher glutathione concentrations were found in hijiki than F. spiralis, which may explain how hijiki deals with its high inorganic arsenic burden. © 2011 CSIRO.

Storage of sediment-associated nutrients and contaminants in river channel and floodplain systems

Samples of fine-grained channel bed sediment and overbank floodplain deposits were collected along the main channels of the Rivers Aire (and its main tributary, the River Calder) and Swale, in Yorkshire, UK, in order to investigate downstream changes in the storage and deposition of heavy metals (Cr, Cu, Pb, Zn), total P and the sum of selected PCB congeners, and to estimate the total storage of these contaminants within the main channels and floodplains of these river systems. Downstream trends in the contaminant content of the <63 μm fraction of channel bed and floodplain sediment in the study rivers are controlled mainly by the location of the main sources of the contaminants, which varies between rivers. In the Rivers Aire and Calder, the contaminant content of the <63 μm fraction of channel bed and floodplain sediment generally increases in a downstream direction, reflecting the location of the main urban and industrialized areas in the middle and lower parts of the basin. In the River Swale, the concentrations of most of the contaminants examined are approximately constant along the length of the river, due to the relatively unpolluted nature of this river. However, the Pb and Zn content of fine channel bed sediment decreases downstream, due to the location of historic metal mines in the headwaters of this river, and the effect of downstream dilution with uncontaminated sediment. The magnitude and spatial variation of contaminant storage and deposition on channel beds and floodplains are also controlled by the amount of <63 μm sediment stored on the channel bed and deposited on the floodplain during overbank events. Consequently, contaminant deposition and storage are strongly influenced by the surface area of the floodplain and channel bed. Contaminant storage on the channel beds of the study rivers is, therefore, generally greatest in the middle and lower reaches of the rivers, since channel width increases downstream. Comparisons of the estimates of total storage of specific contaminants on the channel beds of the main channel systems of the study rivers with the annual contaminant flux at the catchment outlets indicate that channel storage represents <3% of the outlet flux and is, therefore, of limited importance in regulating that flux. Similar comparisons between the annual deposition flux of specific contaminants to the floodplains of the study rivers and the annual contaminant flux at the catchment outlet, emphasise the potential importance of floodplain deposition as a conveyance loss. In the case of the River Aire the floodplain deposition flux is equivalent to between ca. 2% (PCBs) and 36% (Pb) of the outlet flux. With the exception of PCBs, for which the value is ≅0, the equivalent values for the River Swale range between 18% (P) and 95% (Pb). The study emphasises that knowledge of the fine-grained sediment delivery system operating in a river basin is an essential prerequisite for understanding the transport and storage of sediment-associated contaminants in river systems and that conveyance losses associated with floodplain deposition exert an important control on downstream contaminant fluxes and the fate of such contaminants. © 2003 Elsevier Science Ltd. All rights reserved.

The frequency of Environmental Quality Standard (EQS) exceedance for chlorinated organic pollutants in rivers of the Humber catchments

The southern industrial rivers (Aire, Calder, Don and Trent) feeding the Humber estuary were routinely monitored for a range of chlorinated micro- organic contaminants at least once a week over a 1.5-year period. Environmental Quality Standards (EQSs) for inland waters were set under the European Economic Community for a limited number of problematic contaminants (18). The results of the monitoring program for seven classes of chlorinated pollutants on the EQS list are presented in this study. All compounds were detected frequently with the exception of hexachlorobutadiene (where only one detectable measurement out of 280 individual samples occurred). In general, the rivers fell into two classes with respect to their contamination patterns. The Aire and Calder carried higher concentrations of micro- pollutants than the Don and Trent, with the exception of hexachlorobenzene (HCB). For Σ hexachlorocyclohexane (HCH) isomers (α + γ) and for dieldrin, a number of samples (~ 5%) exceeded their EQS for both the Aire and Calder. Often, ΣHCH concentrations were just below the EQS level. Levels of p,p'- DDT on occasions approached the EQS for these two rivers, but only one sample (out of 140) exceeded the EQS. No compounds exceeded their EQS levels on the Don and Trent. Analysis of the ratio of γ HCH/αHCH indicated that the source of HCH for the Don and Trent catchments was primarily lindane (γHCH) and, to a lesser extent, technical HCH (mixture of HCH isomers, dominated by α HCH), while the source(s) for the Aire and Calder had a much higher contribution from technical HCH.