A quality appraisal of economic evaluations of community water fluoridation: A systematic review.

OBJECTIVES: To critically appraise the methodological conduct and reporting quality of economic evaluations (EE) of community water fluoridation (CWF). METHODS: A systematic literature search was conducted in general databases and specialist directories of the economic literature. The Consensus on Health Economic Criteria list (CHEC) appraised the methodological quality while the Consolidated Health Economic Evaluation Reporting Standards (CHEERS) assessed the reporting quality of included studies. RESULTS: A total of 1,138 records were identified, of which 18 met the inclusion criteria. Cost analysis emerged as the most prevalent type of EE, though a growing trend towards conducting full EEs is observed. CHEC revealed the items most frequently unfulfilled were the study design, measurement and valuation of costs and outcomes, while CHEERS also identified reporting deficiencies in these aspects. Furthermore, the review highlights subtleties in methodological aspects that may not be discerned by CHEC, such as the estimation of the impact of fluoridation and the inclusion of treatment savings within cost estimates. CONCLUSIONS: While numerous studies were conducted before publication of these assessment instruments, this review reveals that a noteworthy subset of studies exhibited good methodological conduct and reporting quality. There has been a steady improvement in the methodological and reporting quality over time, with recently published EEs largely adhering to best practice guidelines. The evidence presented will assist policymakers in leveraging the available evidence effectively to inform resource allocation decisions. It may also serve as a resource for researchers to enhance the methodological and reporting standards of future EEs of CWF.

An Improved Evans Blue Staining Method for Consistent, Accurate Assessment of Plasmodiophora brassicae Resting Spore Viability.

Clubroot caused by Plasmodiophora brassicae is an important disease of brassica crops. The use of vital stains to determine the viability of P. brassicae resting spores can provide useful information regarding spore longevity, inoculum potential, or the efficacy of antimicrobial treatments. Evans blue is one example of a vital stain that has been reported to differentially stain viable and nonviable resting spores. Some previously published protocols using Evans blue to stain P. brassicae resting spores have not provided accurate or consistent results. In this study, we modified the Evans blue method by increasing the staining time to 8 h or more and evaluated P. brassicae resting spores after heat treatment at various combinations of temperature and time. Extending staining times significantly increased the numbers of stained resting spores up to 7 h, after which the numbers of stained spores did not change significantly (R2 = 96.88; P ≤ 0.001). The accuracy of the modified method to discriminate viable and nonviable spores was evaluated in repeated experiments and by comparing the staining data with those derived from inoculation assays and propidium monoazide quantitative PCR (qPCR). The results demonstrated that the modified Evans blue staining method improved the accuracy and consistency of measurement of P. brassicae resting spore viability. Additionally, it was equivalent to the qPCR method for differentiating viable and nonviable spores (R2 = 99.84; P ≤ 0.001) and confirmed in canola infection bioassays.

Sustainable treatment systems for removal of pharmaceutical residues and other priority persistent substances.

Pharmaceutical residues and other emerging substances commonly summarised as micropollutants pass through wastewater treatment plants (WWTPs) and end up in the receiving waters and sludge. Many studies have investigated the removal efficiency of various techniques but a holistic evaluation of various relevant treatment alternatives regarding both the removal efficiency for various micropollutants, investment and operating costs, environmental impacts and future comprehensiveness is still lacking. This paper provides the results from a large 3-year project about the evaluation of sustainable treatment systems for removal of various micropollutants or disruptive effects at Swedish WWTPs and their environmental, economic and future sustainability. The presented results are based on our own pilot tests and related assessment and modelling efforts and provide a holistic view on advanced treatment of wastewater for removal of micropollutants.

First Report of Root Rot of Field Pea Caused by Aphanomyces euteiches in Alberta, Canada.

In recent years, root rots have severely impacted yields of field pea (Pisum sativum L.) in the Canadian province of Alberta. Above-normal precipitation levels in the springs of 2011 to 2013 led to the hypothesis that Aphanomyces euteiches Drechsler may play a role in root rot in water-saturated pea fields. To determine causal agent(s) of root rot, 145 pea fields were surveyed at flowering in July 2013 (1). Symptoms of root rot were abundant; the most prominent included red vascular streaking and dark brown rot of the tap root, indicative of Fusarium spp., but brown discoloration and cortical decay of lateral roots, indicative of A. euteiches, was also observed. Total genomic DNA was extracted from diseased root samples from each field, using the Qiagen DNeasy Plant kit, and amplified with species-specific primers for A. euteiches (2). Fusarium spp. were present in all fields, but seven fields located within a 200-km radius yielded a positive reaction for A. euteiches. Five fields were re-visited in May 2014 to collect soil for a bait test (3). Tests were performed using surface-sterilized pea seeds (cv. CDC Meadow) treated with Allegiance FL (Bayer, a.i. metalaxyl) at a rate of 110 ml/kg of seed. Five seeds per pot were planted into field soils in 10-cm pots with 12 replicate pots per field. Soils were irrigated as needed until the second-node stage and then kept at saturation for 14 days. Thirty day-old pea roots were evaluated for root rot symptoms; plated onto cornmeal agar amended with metalaxyl, benomyl, and vancomycin (MBV) without surface sterilization; and visualized microscopically for presence of oospores in the roots. Roots from three out of the five field soils showed symptoms typical of A. euteiches infection, including honey-brown discoloration, degradation of the root cortex, and presence of oospores. Root rot symptoms from the remaining fields were characteristic of Fusarium root rot, and oospores were not observed in roots. Fungal cultures with fast-growing, white, aerial mycelia characteristic of A. euteiches on MBV, were recovered from roots with Aphanomyces root rot symptoms, and transferred to PDA. To confirm pathogen identity, total DNA was extracted from 7-day-old cultures growing on PDA using the Qiagen DNeasy Plant Kit. The ribosomal DNA internal transcribed spacer (ITS) region was amplified using the primer pair ITS1 and ITS4 and sequenced (4). The sequences, deposited in GenBank with accession numbers KM486065, KM486066, and KM486067, were 100% identical to the ITS rDNA sequence of several isolates of A. euteiches using a BLASTn query. Fusarium spp. were also recovered from all root samples in the soil bait test. Total DNA extracted from roots was used in PCR assays with A. euteiches-specific primers as described above. PCR amplification of root DNA was successful only from the same three fields that showed Aphanomcyces root rot symptoms, further verifying presence of A. euteiches. The inability to detect or recover A. euteiches from two fields that had tested positive in the survey was likely due to patchy distribution of this pathogen and emphasizes the importance of rigorous soil collection methods to accurately detect pathogens. Although this is the first record of A. euteiches on field pea in Alberta, the distribution of A. euteiches within a 200-km radius in southern Alberta indicates that it has likely been present in soils for several years. The interaction between A. euteiches and Fusarium spp. infection in the root rot complex of field pea and their impact on field pea production in Alberta is currently being investigated. References: (1) S. Chatterton et al. Can. Plant Dis. Surv. 94:189, 2014. (2) C. Gangneux et al. Phytopathology 104:1138, 2014. (3) D. Malvick et al. Plant Dis. 78:361, 1994. (4) T. J. White et al. Page 315 in: PCR Protocols: A Guide to Methods and Applications. Academic Press, San Diego, 1990.

Differential regulation of simultaneous antitumor and alloreactive CD8(+) T-cell responses in the same host by rapamycin.

Rapamycin is an immunosuppressive agent routinely used in organ transplantation but also paradoxically exerts antiviral and antitumor activities. Pathogen-specific memory CD8(+) T-cell (T(CD8) ) responses were recently found to be augmented by rapamycin. However, whether rapamycin influences the magnitude and quality of anticancer T(CD8) responses is unknown. Importantly, how rapamycin may regulate simultaneous virus/tumor-specific and alloreactive T(CD8) in the same host remains unexplored. To answer these questions, we primed wild-type mice with allogeneic cells concomitantly expressing simian virus 40 large tumor antigen (T Ag), a viral oncoprotein with well-defined epitopes. Rapamycin selectively enhanced the cross-priming of T(CD8) specific for T Ag's most immunodominant epitope called site IV but not T(CD8) alloreactivity. Rapamycin-treated mice also had a high percentage of splenic CD127(high) KLRG1(low) T(CD8) and an increased frequency of site IV-specific T cells long after the peak of their primary response. When site IV was presented as a cytosolic minigene encoded by a recombinant vaccinia virus, rapamycin failed to boost the site IV-specific response. Therefore, the nature and presentation mode of antigen determine the susceptibility to the adjuvant effect of rapamycin. Our findings reveal the unexpected benefit of rapamycin treatment in recipients of allografts co-expressing tumor/viral Ags.

Milestones in oral health services in the Republic of Ireland.

With the many changes occurring in Ireland it would seem an opportune time to review the body of research conducted and policy enacted in the Republic of Ireland on oral health services and oral health. The dental health of the nation prior to water fluoridation, the legislation and policy decisions impacting on oral health up to budgetary changes, and the production of evidence-based guidelines will be discussed. The first national survey of dental health was conducted in Ireland in 1952 - 'Dental Caries in Ireland'. In the intervening 60 years, further surveys of the oral health of people in Ireland have been carried out. Legislation, surveys and policy documents that have shaped dentistry and the oral health of the population are set out in Tables 1 and 2. A more comprehensive description of the policies can be found in the thesis submitted in fulfilment of Masters in Dental Public Health (MDPH) by the lead author.

Characteristics of wastewater originating from dental practices using predominantly mercury-free dental materials.

Dental materials are currently undergoing a revolution. Mercury use, including traditional amalgam (mercury-containing) material used in dental fillings, is now being widely regulated under the Minamata convention, and dental amalgam is currently being replaced by resin formulations in dentistry. These resin-based materials can be tuned to offer varying material properties by incorporation of a range of nano- and micro-particle based 'fillers' for different dental properties and applications. However, these innovations may have a concomitant effect on the waste streams associated with common dental applications, in particular the potential for higher concentrations of novel micro- and nanomaterials within wastewater streams, and a potential route for novel nanomaterials into the wider Environment. These new materials may also mean that wastewater filtering apparatus commonly deployed at present, such as amalgam separators, may be less efficient or insufficient to capture these new filler materials in dental facility wastewater. In this work, we analyse dental wastewater streams from three dental facilities in Ireland with differing amalgam separators in place. The potential overall toxicity, particulate load and physicochemical properties are analysed. The overall risk posed by these new materials is also discussed.

Ultrasonic testing of thick and thin Inconel 625 alloys manufactured by laser powder bed fusion.

Additive manufacturing of alloys enables low-volume production of functional metallic components with complex geometries. Ultrasonic testing can ensure the quality of these components and detect typical defects generated during laser powder bed fusion (LPBF). However, it is difficult to find a single ultrasonic inspection technique that can detect defects in the large variety of geometries generated using LPBF. In this work, phased array ultrasonic testing (PAUT) is suggested to inspect thick LPBF components, while guided waves are explored for thin curved ones. PAUT is used to detect cylindrical lack of fusion defects in thick LPBF rectangular parts. Practical defects are generated by reducing the laser power at prespecified locations in the samples. The defects' shape and density are verified using optical microscopy and X-ray computed tomography. Partially fused defects down to 0.25 mm in diameter are experimentally detected using a 10 MHz PAUT probe with the total focusing method post-processing. The experimental results are compared to defect images predicted by finite element simulations. For thin components with curved geometry, guided waves are used to detect powder-filled cylindrical defects. The waves are generated using piezoelectric transducers, and the spatiotemporal wavefield is measured using a scanning laser Doppler vibrometer. Using root-mean-square imaging of the wavefield, defects down to 1 mm are clearly detected despite the complex internal features in the samples.

Complementary catalysis and analysis within solid state additively manufactured metal micro flow reactors.

Additive Manufacturing is transforming how researchers and industrialists look to design and manufacture chemical devices to meet their specific needs. In this work, we report the first example of a flow reactor formed via the solid-state metal sheet lamination technique, Ultrasonic Additive Manufacturing (UAM), with directly integrated catalytic sections and sensing elements. The UAM technology not only overcomes many of the current limitations associated with the additive manufacturing of chemical reactionware but it also significantly increases the functionality of such devices. A range of biologically important 1, 4-disubstituted 1, 2, 3-triazole compounds were successfully synthesised and optimised in-flow through a Cu mediated Huisgen 1, 3-dipolar cycloaddition using the UAM chemical device. By exploiting the unique properties of UAM and continuous flow processing, the device was able to catalyse the proceeding reactions whilst also providing real-time feedback for reaction monitoring and optimisation.

A new index to measure tooth wear--methodolgy and practical advice.

A new tooth wear index, designed to measure stages of tooth wear in enamel and dentine is presented. The index measures the lateral spread of wear in enamel and the depth of tooth wear in dentine. The index scores enamel loss at 5 levels and 6 levels in dentine and provides a more sensitive index for monitoring the progression of wear than older indices. The protocols and methods of the index are described and incorporate refinements based on the combined experiences of two independent studies conducted on adults and children. The findings of both studies are summarised and recommendations are made for future studies which investigate the prevalence of tooth wear in adults or children.

Impact of Reducing Water Fluoride on Dental Caries and Fluorosis.

Guidance intended to reduce fluoride toothpaste ingestion in early childhood was introduced in Ireland in 2002. In 2007, water fluoride concentration was adjusted from 0.8-1.0 to 0.6-0.8 ppm. The objective of this study was to determine the difference in caries and fluorosis levels following introduction of these 2 policy measures. A before-and-after study compared caries and fluorosis in random samples of 8-y-olds in Dublin (n = 707) and Cork-Kerry (n = 1148) in 2017 with 8-y-olds in Dublin (n = 679) and Cork-Kerry (n = 565) in 2002. Dentinal caries experience (primary teeth, d3vcmft(cde)) and fluorosis (permanent teeth, Dean's index of very mild or higher) were clinically measured. Lifetime exposure to community water fluoridation (CWF) was classified as "full CWF"/"no CWF." Effect of examination year on caries prevalence and severity and fluorosis prevalence was assessed using multivariate regression adjusting for other explanatory variables. There was little change in commencement of fluoride toothpaste use at ≤24 mo following introduction of toothbrushing guidance. Among children with full CWF, there was no statistically significant difference in caries prevalence or severity between 2017 and 2002. In 2017, caries prevalence was 55% in Dublin (full CWF) and 56% in Cork-Kerry (full CWF), and mean d3vcmft(cde) among children with caries was 3.4 and 3.7, respectively. Caries severity was less in 2017 (mean 4.2) than 2002 (mean 4.9) among children with no CWF (P = 0.039). The difference in caries severity between children with full CWF and no CWF was less in 2017 than in 2002 (interaction P = 0.013), suggesting a reduced benefit for CWF in 2017. In 2017, fluorosis prevalence was 18% in Dublin (full CWF) and 12% in Cork-Kerry (full CWF). Fluorosis was predominantly "very mild" with no statistically significant difference between 2017 and 2002. CWF at 0.6 to 0.8 ppm is an effective caries-preventive measure. Results suggested low uptake of toothbrushing guidance, a reduced caries-preventive effect for CWF in primary teeth, and no reduction in fluorosis following introduction of the policy measures.

Is tooth wear in the primary dentition predictive of tooth wear in the permanent dentition? Report from a longitudinal study.

OBJECTIVES: To determine the prevalence of tooth wear in the permanent dentition of a sample of 12-year-old school children and establish whether an association exists between tooth wear recorded now and tooth wear recorded in their primary dentition at age five. DESIGN: A prospective cohort study. METHODS: At follow-up to a previous study complete data were available for 123 children; fieldwork was conducted in the child's primary school. Measurement of tooth wear used a scoring system modified from the Smith and Knight Tooth Wear Index (TWI). Tooth wear which had progressed to dentine was assessed on the occlusal surfaces of the four first permanent molars, the labial, lingual/palatal and incisal surfaces of the six upper and six lower anterior teeth; a total of 40 scoreable surfaces. Demographic data were collected from the parents, and a questionnaire on oral hygiene habits, diet and behaviours was completed by each child. RESULTS: In total 38% (n = 47) of subjects had tooth wear, if incisor teeth only were included, 33% (n = 40) had tooth wear and similarly if the occlusal surfaces of molar teeth only were included 10% (n = 12) had signs of tooth wear. Gender was significantly associated with tooth wear: males had more tooth wear. The presence of tooth wear with dentine exposed in the primary dentition was significantly associated with tooth wear on the occlusal surfaces of the first permanent molars. CONCLUSION: Males had more tooth wear than females. An association existed between tooth wear recorded at age 5 and molar tooth wear recorded at age 12. Tooth wear is a lifelong cumulative process and should be recorded in both the primary and permanent dentitions.

Frequency-comb spectroscopy on pure quantum states of a single molecular ion.

Spectroscopy is a powerful tool for studying molecules and is commonly performed on large thermal molecular ensembles that are perturbed by motional shifts and interactions with the environment and one another, resulting in convoluted spectra and limited resolution. Here, we use quantum-logic techniques to prepare a trapped molecular ion in a single quantum state, drive terahertz rotational transitions with an optical frequency comb, and read out the final state nondestructively, leaving the molecule ready for further manipulation. We can resolve rotational transitions to 11 significant digits and derive the rotational constant of 40CaH+ to be B R = 142 501 777.9(1.7) kilohertz. Our approach is suited for a wide range of molecular ions, including polyatomics and species relevant for tests of fundamental physics, chemistry, and astrophysics.

Cyclophilin: a specific cytosolic binding protein for cyclosporin A.

Cyclophilin, a specific cytosolic binding protein responsible for the concentration of the immunosuppressant cyclosporin A by lymphoid cells, was purified to homogeneity from bovine thymocytes. Cation-exchange high-performance liquid chromatography resolved a major and minor cyclophilin species that bind cyclosporin A with a dissociation constant of about 2 X 10(-7) moles per liter and specific activities of 77 and 67 micrograms per milligram of protein, respectively. Both cyclophilin species have an apparent molecular weight of 15,000, an isoelectric point of 9.6, and nearly identical amino acid compositions. A portion of the NH2-terminal amino acid sequence of the major species was determined. The cyclosporin A-binding activity of cyclophilin is sulfhydryl dependent, unstable at 56 degrees C and at pH 4 or 9.5, and sensitive to trypsin but not to chymotrypsin digestion. Cyclophilin specifically binds a series of cyclosporin analogs in proportion to their activity in a mixed lymphocyte reaction. Isolation of cyclophilin from the cytosol of thymocytes suggests that the immunosuppressive activity of cyclosporin A is mediated by an intracellular mechanism, not by a membrane-associated mechanism.

Altered cytokine export and apoptosis in mice deficient in interleukin-1 beta converting enzyme.

The interleukin-1 beta (IL-1 beta) converting enzyme (ICE) processes the inactive IL-1 beta precursor to the proinflammatory cytokine. Adherent monocytes from mice harboring a disrupted ICE gene (ICE-/-) did not export IL-1 beta or interleukin-1 alpha (IL-1 alpha) after stimulation with lipopolysaccharide. Export of tumor necrosis factor-alpha and interleukin-6 (IL-6) from these cells was also diminished. Thymocytes from ICE-/- mice were sensitive to apoptosis induced by dexamethasone or ionizing radiation, but were resistant to apoptosis induced by Fas antibody. Despite this defect in apoptosis, ICE-/- mice proceed normally through development.

Activation of interferon-gamma inducing factor mediated by interleukin-1beta converting enzyme.

The interleukin-1beta (IL-1beta) converting enzyme (ICE) processes the inactive IL-1beta precursor to the proinflammatory cytokine. ICE was also shown to cleave the precursor of interferon-gamma inducing factor (IGIF) at the authentic processing site with high efficiency, thereby activating IGIF and facilitating its export. Lipopolysaccharide-activated ICE-deficient (ICE-/-) Kupffer cells synthesized the IGIF precursor but failed to process it into the active form. Interferon-gamma and IGIF were diminished in the sera of ICE-/- mice exposed to Propionibacterium acnes and lipopolysaccharide. The lack of multiple proinflammatory cytokines in ICE-/- mice may account for their protection from septic shock.

In-situ time resolved spectrographic measurement using an additively manufactured metallic micro-fluidic analysis platform.

INTRODUCTION: Microfluidic reactionware allows small volumes of reagents to be utilized for highly controlled flow chemistry applications. By integrating these microreactors with onboard analytical systems, the devices change from passive ones to active ones, increasing their functionality and usefulness. A pressing application for these active microreactors is the monitoring of reaction progress and intermediaries with respect to time, shedding light on important information about these real-time synthetic processes. OBJECTIVE: In this multi-disciplinary study the objective was to utilise advanced digital fabrication to research metallic, active microreactors with integrated fibre optics for reaction progress monitoring of solvent based liquids, incompatible with previously researched polymer devices, in combination with on-board Ultraviolet-visible spectroscopy for real-time reaction monitoring. METHOD: A solid-state, metal-based additive manufactured system (Ultrasonic Additive Manufacturing) combined with focussed ion beam milling, that permitted the accurate embedment of delicate sensory elements directly at the point of need within aluminium layers, was researched as a method to create active, metallic, flow reactors with on-board sensing. This outcome was then used to characterise and correctly identify concentrations of UV-active water-soluble B-vitamin nicotinamide and fluorescein. A dilution series was formed from 0.01-1.75 mM; which was pumped through the research device and monitored using UV-vis spectroscopy. RESULTS: The results uniquely showed the in-situ ion milling of ultrasonically embedded optical fibres resulted in a metallic microfluidic reaction and monitoring device capable of measuring solvent solutions from 18 µM to 18 mM of nicotinamide and fluorescein, in real time. This level of accuracy highlights that the researched device and methods are capable of real-time spectrographic analysis of a range of chemical reactions outside of those possible with polymer devices.

The heat shock response in HeLa cells is accompanied by elevated expression of the c-fos proto-oncogene.

Several known inducers of the heat shock response (heat stress, arsenite, and heavy metals) were shown to cause a significant elevation of c-fos mRNA in HeLa cells. Heat stress resulted in a time- and temperature-dependent prolonged elevation in the level of c-fos mRNA, which was accompanied by increased translation of c-fos protein and its appearance in the nucleus. Elevated expression of c-fos during heat stress was paralleled by induction of hsp 70 mRNA, while levels of c-myc and metallothionein mRNAs declined. Treatment of HeLa cells with arsenite or heavy metals also resulted in increased levels of hsp 70, as well as c-fos mRNA. Although elevated expression of c-fos was prevented by inhibitors of RNA synthesis, analysis of relative rates of gene transcription showed that during heat stress there was a negligible change in c-fos transcription. Therefore, the enhanced expression of c-fos during the heat shock response is likely to occur primarily through posttranscriptional processes. Cycloheximide was also shown to significantly increase the c-fos mRNA level in HeLa cells. There results are consistent with the observation that these inducers of the heat shock response, as well as cycloheximide, repress protein synthesis and suggest that the increase in the level of c-fos mRNA is caused by an inhibition of protein synthesis. This supports the hypothesis that c-fos mRNA is preferentially stabilized under conditions which induce the heat shock response, perhaps by decreased synthesis of a short-lived protein which regulates c-fos mRNA turnover.

Does breastfeeding duration decrease child obesity? An instrumental variables analysis.

BACKGROUND: Many studies have documented that breastfeeding is associated with a significant reduction in child obesity risk. However, a persistent problem in this literature is that unobservable confounders may drive the correlations between breastfeeding behaviors and child weight outcomes. OBJECTIVE: This study examines the effect of breastfeeding practices on child weight outcomes at age 2. METHODS: This study relied on population-based data for all births in Oregon in 2009 followed for two years. We used instrumental variables methods to exploit variations in breastfeeding by mothers immediately after delivery and the degree to which hospitals encouraged mothers to breastfeed in order to isolate the effect of breastfeeding practices on child weight outcomes. RESULTS: We found that for every extra week that the child was breastfed, the likelihood of the child being obese at age 2 declined by 0.82% [95% CI -1.8% to 0.1%]. Likewise, for every extra week that the child was exclusively breastfed, the likelihood of being obese declined by 0.66% [95% CI -1.4 to 0.06%]. While the magnitudes of effects were modest and marginally significant, the results were robust in a variety of specifications. CONCLUSION: The results suggest that hospital practices that support breastfeeding may influence childhood weight outcomes.

Human milk vacuolating cytotoxin A immunoglobulin A antibodies modify Helicobacter pylori infection in Gambian children.

We collected data, including the weights, urea breath test results, and presence of maternal milk cytotoxin-associated gene-specific and vacuolating cytotoxin A-specific immunoglobulin A monthly from 48 mothers and infants (to 44 weeks of age) in The Gambia. In all, 11 children (23%) had negative urea breath test results, and 37 (77%) had positive results. Weight loss associated with Helicobacter pylori colonization was restricted to children whose mothers did not produce anti-vacuolating cytotoxin A antibodies in their milk (P=.028, by t test).