Susceptibility of microcosm subgingival dental plaques to lethal photosensitisation

Photodynamic therapy (PDT) offers potential as a non-invasive treatment of periodontal 15 disease. In this study, microcosm biofilms were grown in vitro under conditions designed 16 to mimic subgingival plaques typically found in patients with periodontitis. To 17 investigate potential PDT modalities, biofilms were exposed to light from a helium/neon 18 laser in conjunction with a photosensitiser, toluidine blue (TBO), at varying output and 19 concentration, respectively. To determine cytotoxic effects, viability profiling was 20 undertaken on whole biofilms using standard plating methods, and on horizontal cross-21 sections of biofilms using confocal laser-scanning microscopy (CLSM) in conjunction 22 with a differential viability stain. A light energy dose of 94.5 J in combination with 81.7 23 .M TBO was found to be optimal, achieving significant kills of over 97%. CLSM 24 enabled visualisation of the effects of PDT in three dimensions. Viability profiling of the 25 CLSM images revealed that lethal photosensitisation was most effective in the upper 26 layers of biofilm. PDT was found to reduce the viability of subgingivally-modelled 27 plaques in vitro by a similar magnitude to chlorhexidine digluconate (CHL), which is 28 commonly used to treat periodontal disease. The findings of this study indicate that PDT 29 may be an effective alternative to conventional modalities in the treatment of periodontal 30 disease. 3

Evolution of deep-sea sediments across the Paleocene-Eocene and Eocene-Oligocene boundaries

The composition and distribution of deep-sea sediments is the result of a multitude of climatic, biotic and oceanic conditions relating to biogeochemical cycles and environmental change. Here we utilize the extensive sediment archives of the International Ocean Discovery Program (IODP) and its predecessors to construct maps of deep-sea sediment type across two critical but contrasting boundaries in the Paleogene, one characterised by an interval of extreme warmth (Paleocene/Eocene) and the other by global cooling (Eocene/Oligocene). Ocean sediment distribution shows significant divergence both between the latest Paleocene and Paleocene Eocene Thermal Maximum (PETM), across the Eocene-Oligocene Transition (EOT), and in comparison to modern sediment distributions. Carbonate sedimentation in the latest Paleocene extends to high southern latitudes. Disappearance of carbonate sediments at the PETM is well documented and can be attributed to dissolution caused by significant ocean acidification as a result of carbon-cycle perturbation. Biosiliceous sediments are rare and it is posited that the reduced biogenic silica deposition at the equator is commensurate with an overall lack of equatorial upwelling in the early Paleogene ocean. In the Southern Ocean, we attribute the low in biosiliceous burial, to the warm deep water temperatures which would have impacted biogenic silica preservation. In the late Eocene, our sediment depositional maps record a tongue of radiolarian ooze in the eastern equatorial Pacific. Enhanced biosiliceous deposits in the late Eocene equatorial Pacific and South Atlantic are due to increased productivity and the spin-up of the oceans. Our compilation documents the enhanced global carbonate sedimentation in the early Oligocene, confirming that the drop in the carbonate compensation depth was global

Border Terriers under primary veterinary care in England: demography and disorders

The Border Terrier is a working terrier type that is generally considered to be a relatively healthy and hardy breed. This study aimed to characterise the demography and common disorders of Border Terriers receiving veterinary care in England using de-identified electronic patient record data within the VetCompass™ Programme

Second-generation nitazoxanide derivatives: thiazolides are effective inhibitors of the influenza A virus

Aim: The only small molecule drugs currently available for treatment of influenza A virus (IAV) are M2 ion channel blockers and sialidase inhibitors. The prototype thiazolide, nitazoxanide, has successfully completed Phase III clinical trials against acute uncomplicated influenza. Results: We report the activity of seventeen thiazolide analogs against A/PuertoRico/8/1934(H1N1), a laboratory-adapted strain of the H1N1 subtype of IAV, in a cell culture-based assay. A total of eight analogs showed IC50s in the range of 0.14–5.0 μM. Additionally a quantitative structure–property relationship study showed high correlation between experimental and predicted activity based on a molecular descriptor set. Conclusion: A range of thiazolides show useful activity against an H1N1 strain of IAV. Further evaluation of these molecules as potential new small molecule therapies is justified

Health-related welfare prioritisation of canine disorders using electronic health records in primary care practice in the UK

Background: Evidence-based comparison of the disorder-specific welfare burdens of major canine conditions could better inform targeting of stakeholder resources, to maximise improvement of health-related welfare in UK dogs. Population-level disease related welfare impact offers a quantitative, welfare-centred framework for objective disorder prioritisation, but practical applications have been limited to date due to sparse reliable evidence on disorder-specific prevalence, severity and duration across the canine disease spectrum. The VetCompass™ Programme collects de-identified electronic health record data from dogs attending primary-care clinics UK-wide, and is well placed to fill these information gaps. Results: The eight common, breed-related conditions assessed were anal sac disorder, conjunctivitis, dental disease, dermatitis, overweight/obese, lipoma, osteoarthritis and otitis externa. Annual period prevalence estimates (based on confirming 250 cases from total potential cases identified from denominator population of 455, 557 dogs) were highest for dental disorder (9.6%), overweight/obese (5.7%) and anal sac disorder (4.5%). Dental disorder (76% of study year), osteoarthritis (82%), and overweight/obese (70%) had highest annual duration scores. Osteoarthritis (scoring 13/21), otitis externa (11/21) and dermatitis demonstrated (10/21) highest overall severity scores. Dental disorder (2.47/3.00 summative score), osteoarthritis (2.24/3.00) and overweight/obese (1.67/3.00) had highest VetCompass Welfare Impact scores overall. Discussion: Of the eight common, breed-related disorders assessed, dental disorder, osteoarthritis and overweight/obese demonstrated particular welfare impact, based on combinations of high prevalence, duration and severity. Future work could extend this methodology to cover a wider range of disorders. Conclusions: Dental disorders, osteoarthritis and overweight/obese have emerged as priority areas for health-related welfare improvement in the UK dog population. This study demonstrated applicability of a standardised methodology to assess the relative health-related welfare impact across a range of canine disorders using VetCompass clinical data

Demography and disorders of German Shepherd Dogs under primary veterinarycare in the UK

The German Shepherd Dog (GSD) has been widely used for a variety of working roles. However, concerns for the health and welfare of the GSD have been widely aired and there is evidence that breed numbers are now in decline in the UK. Accurate demographic and disorder data could assist with breeding and clinical prioritisation. The VetCompassTM Programme collects clinical data on dogs under primary veterinary care in the UK. This study included all VetCompassTM dogs under veterinary care during 2013. Demographic, mortality and clinical diagnosis data on GSDs were extracted and reported

The Scenario Model Intercomparison Project (ScenarioMIP) for CMIP6

Model experiment description paperProjections of future climate change play a fundamental role in improving understanding of the climate system as well as characterizing societal risks and response options. The Scenario Model Intercomparison Project (ScenarioMIP) is the primary activity within Phase 6 of the Coupled Model Intercomparison Project (CMIP6) that will provide multi-model climate projections based on alternative scenarios of future emissions and land use changes produced with integrated assessment models. In this paper, we describe ScenarioMIP's objectives, experimental design, and its relation to other activities within CMIP6. The ScenarioMIP design is one component of a larger scenario process that aims to facilitate a wide range of integrated studies across the climate science, integrated assessment modeling, and impacts, adaptation, and vulnerability communities, and will form an important part of the evidence base in the forthcoming Intergovernmental Panel on Climate Change (IPCC) assessments. At the same time, it will provide the basis for investigating a number of targeted science and policy questions that are especially relevant to scenario-based analysis, including the role of specific forcings such as land use and aerosols, the effect of a peak and decline in forcing, the consequences of scenarios that limit warming to below 2 °C, the relative contributions to uncertainty from scenarios, climate models, and internal variability, and long-term climate system outcomes beyond the 21st century. To serve this wide range of scientific communities and address these questions, a design has been identified consisting of eight alternative 21st century scenarios plus one large initial condition ensemble and a set of long-term extensions, divided into two tiers defined by relative priority. Some of these scenarios will also provide a basis for variants planned to be run in other CMIP6-Endorsed MIPs to investigate questions related to specific forcings. Harmonized, spatially explicit emissions and land use scenarios generated with integrated assessment models will be provided to participating climate modeling groups by late 2016, with the climate model simulations run within the 2017-2018 time frame, and output from the climate model projections made available and analyses performed over the 2018-2020 period.CRESCENDO project members (V. Eyring, P. Friedlingstein, E. Kriegler, R. Knutti, J. Lowe, K. Riahi, D. van Vuuren) acknowledge funding received from the Horizon 2020 European Union’s Framework Programme for Research and Innovation under grant agreement no. 641816. C. Tebaldi, G. A. Meehl and B. M. Sanderson acknowledge the support of the Regional and Global Climate Modeling Program (RGCM) of the U.S. Department of Energy’s, Office of Science (BER), Cooperative Agreement DE-FC02-97ER6240

Influence of arthritis and non-arthritis related factors on areal bone mineral density (BMDa) in women with longstanding inflammatory polyarthritis: a primary care based inception cohort

<p>Abstract</p> <p>Background</p> <p>The aim of this analysis was to determine the relative influence of disease and non-disease factors on areal bone mineral density (BMD_a) in a primary care based cohort of women with inflammatory polyarthritis.</p> <p>Methods</p> <p>Women aged 16 years and over with recent onset inflammatory polyarthritis were recruited to the Norfolk Arthritis Register (NOAR) between 1990 and 1993. Subjects were examined at both baseline and follow up for the presence of tender, swollen and deformed joints. At the 10^thanniversary visit, a sub-sample of women were invited to complete a bone health questionnaire and attend for BMD_a(Hologic, QDR 4000). Linear regression was used to examine the association between BMD_awith both (i) arthritis-related factors assessed at baseline and the 10^thanniversary visit and (ii) standard risk factors for osteoporosis. Adjustments were made for age.</p> <p>Results</p> <p>108 women, mean age 58.0 years were studied. Older age, decreasing weight and BMI at follow up were all associated with lower BMD_aat both the spine and femoral neck. None of the lifestyle factors were linked. Indices of joint damage including 10^thanniversary deformed joint count and erosive joint count were the arthritis-related variables linked with a reduction in BMD_aat the femoral neck. By contrast, disease activity as determined by the number of tender and or swollen joints assessed both at baseline and follow up was not linked with BMD_aat either site.</p> <p>Conclusion</p> <p>Cumulative disease damage was the strongest predictor of reduced femoral bone density. Other disease and lifestyle factors have only a modest influence.</p

Validity of measures of pain and symptoms in HIV/AIDS infected households in resources poor settings: results from the Dominican Republic and Cambodia

BACKGROUND: HIV/AIDS treatment programs are currently being mounted in many developing nations that include palliative care services. While measures of palliative care have been developed and validated for resource rich settings, very little work exists to support an understanding of measurement for Africa, Latin America or Asia. METHODS: This study investigates the construct validity of measures of reported pain, pain control, symptoms and symptom control in areas with high HIV-infected prevalence in Dominican Republic and Cambodia Measures were adapted from the POS (Palliative Outcome Scale). Households were selected through purposive sampling from networks of people living with HIV/AIDS. Consistencies in patterns in the data were tested used Chi Square and Mantel Haenszel tests. RESULTS: The sample persons who reported chronic illness were much more likely to report pain and symptoms compared to those not chronically ill. When controlling for the degrees of pain, pain control did not differ between the chronically ill and non-chronically ill using a Mantel Haenszel test in both countries. Similar results were found for reported symptoms and symptom control for the Dominican Republic. These findings broadly support the construct validity of an adapted version of the POS in these two less developed countries. CONCLUSION: The results of the study suggest that the selected measures can usefully be incorporated into population-based surveys and evaluation tools needed to monitor palliative care and used in settings with high HIV/AIDS prevalence