Leeds Dental Hospital

Dental diseases are among the most prevalent and costly diseases affecting industrialized societies, and yet are highly preventable. The microflora of dental plaque biofilms from diseased sites is distinct from that found in health, although the putative pathogens can often be detected in low numbers at normal sites. In dental caries, there is a shift towards community dominance by acidogenic and acid-tolerant Gram-positive bacteria (e.g. mutans streptococci and lactobacilli) at the expense of the acid-sensitive species associated with sound enamel. In contrast, the numbers and proportions of obligately anaerobic bacteria, including Gram-negative proteolytic species, increase in periodontal diseases. Modelling studies using defined consortia of oral bacteria grown in planktonic and biofilm systems have been undertaken to identify environmental factors responsible for driving these deleterious shifts in the plaque microflora. Repeated conditions of low pH (rather than sugar availability per se) selected for mutans streptococci and lactobacilli, while the introduction of novel host proteins and glycoproteins (as occurs during the inflammatory response to plaque), and the concomitant rise in local pH, enriched for Gram-negative anaerobic and asaccharolytic species. These studies emphasized (a). significant properties of dental plaque as both a biofilm and a microbial community, and (b). the dynamic relationship existing between the environment and the composition of the oral microflora. This research resulted in a novel hypothesis (the 'ecological plaque hypothesis') to better describe the relationship between plaque bacteria and the host in health and disease. Implicit in this hypothesis is the concept that disease can be prevented not only by directly inhibiting the putative pathogens, but also by interfering with the environmental factors driving the selection and enrichment of these bacteria. Thus, a more holistic approach can be taken in disease control and management strategies.

Dental plaque is a structurally- and functionally-organized biofilm. Plaque forms in an ordered way and has a diverse microbial composition that, in health, remains relatively stable over time (microbial homeostasis). The predominant species from diseased sites are different from those found in healthy sites, although the putative pathogens can often be detected in low numbers at normal sites. In dental caries, there is a shift toward community dominance by acidogenic and acid-tolerating species such as mutans streptococci and lactobacilli, although other species with relevant traits may be involved. Strategies to control caries could include inhibition of biofilm development (e.g. prevention of attachment of cariogenic bacteria, manipulation of cell signaling mechanisms, delivery of effective antimicrobials, etc.), or enhancement of the host defenses. Additionally, these more conventional approaches could be augmented by interference with the factors that enable the cariogenic bacteria to escape from the normal homeostatic mechanisms that restrict their growth in plaque and out compete the organisms associated with health. Evidence suggests that regular conditions of low pH in plaque select for mutans streptococci and lactobacilli. Therefore, the suppression of sugar catabolism and acid production by the use of metabolic inhibitors and non-fermentable artificial sweeteners in snacks, or the stimulation of saliva flow, could assist in the maintenance of homeostasis in plaque. Arguments will be presented that an appreciation of ecological principles will enable a more holistic approach to be taken in caries control.

BACKGROUND: In this paper, we report the findings of a realist synthesis that aimed to understand how and in what circumstances patient reported outcome measures (PROMs) support patient-clinician communication and subsequent care processes and outcomes in clinical care. We tested two overarching programme theories: (1) PROMs completion prompts a process of self-reflection and supports patients to raise issues with clinicians and (2) PROMs scores raise clinicians' awareness of patients' problems and prompts discussion and action. We examined how the structure of the PROM and care context shaped the ways in which PROMs support clinician-patient communication and subsequent care processes. RESULTS: PROMs completion prompts patients to reflect on their health and gives them permission to raise issues with clinicians. However, clinicians found standardised PROMs completion during patient assessments sometimes constrained rather than supported communication. In response, clinicians adapted their use of PROMs to render them compatible with the ongoing management of patient relationships. Individualised PROMs supported dialogue by enabling the patient to tell their story. In oncology, PROMs completion outside of the consultation enabled clinicians to identify problematic symptoms when the PROM acted as a substitute rather than addition to the clinical encounter and when the PROM focused on symptoms and side effects, rather than health related quality of life (HRQoL). Patients did not always feel it was appropriate to discuss emotional, functional or HRQoL issues with doctors and doctors did not perceive this was within their remit. CONCLUSIONS: This paper makes two important contributions to the literature. First, our findings show that PROMs completion is not a neutral act of information retrieval but can change how patients think about their condition. Second, our findings reveal that the ways in which clinicians use PROMs is shaped by their relationships with patients and professional roles and boundaries. Future research should examine how PROMs completion and feedback shapes and is influenced by the process of building relationships with patients, rather than just their impact on information exchange and decision making.

Schools provide an important setting for promoting health, as they reach over 1 billion children worldwide and, through them, the school staff, families and the community as a whole. Health promotion messages can be reinforced throughout the most influential stages of children's lives, enabling them to develop lifelong sustainable attitudes and skills. Poor oral health can have a detrimental effect on children's quality of life, their performance at school and their success in later life. This paper examines the global need for promoting oral health through schools. The WHO Global School Health Initiative and the potential for setting up oral health programmes in schools using the health-promoting school framework are discussed. The challenges faced in promoting oral health in schools in both developed and developing countries are highlighted. The importance of using a validated framework and appropriate methodologies for the evaluation of school oral health projects is emphasized.

Pseudogenes are commonly encountered during investigation of the genomes of a wide range of life forms. This review concentrates on vertebrate, and in particular mammalian, pseudogenes and describes their origin and subsequent evolution. Consideration is also given to pseudogenes that are transcribed and to the unusual group of genes that exist at the interface between functional genes and non-functional pseudogenes. As the sequences of different genomes are characterised, the recognition and interpretation of pseudogene sequences will become more important and have a greater impact in the field of molecular genetics.

OBJECTIVES: The objective of this study was to analyze the development of implant stability by repeated resonance frequency analysis (RFA) measurements during 1 year in 23 patients treated according to an immediate/early-loading protocol. The objective was also to evaluate the possible differences between failing and successful implants. MATERIAL AND METHODS: Eighty-one Brånemark System implants were placed in 23 patients for immediate/early-occlusal loading in all jaw regions. Thirty of the implants were placed in extraction sockets and 62 were subjected to GBR procedures. Apart from clinical and radiographic examinations, the patients were followed with RFA at placement, prosthesis connection and after 1-3, 6 and 12 months. Statistical analyses were carried out to study the possible differences between implants that failed during the study period and implants that remained successful. RESULTS: Nine implants failed (11.2%) during the 1 year of loading. RFA showed a distinct different pattern between the implants that remained stable and the implants that were lost. The implants that failed during the course of the study showed a significantly lower stability already after 1 month. CONCLUSION: Within the limitations of this study, it is concluded that failing implants show a continuous decrease of stability until failure. Low RFA levels after 1 and 2 months seem to indicate an increased risk for future failure. This information may be used to avoid implant failure in the future by unloading implants with decreasing degree of stability with time as diagnosed with the RFA technique.

Rationally designed beta-sheet-forming peptides that spontaneously form three-dimensional fibrillar scaffolds in response to specific environmental triggers may potentially be used in skeletal tissue engineering, including the treatment/prevention of dental caries, via bioactive surface groups. We hypothesized that infiltration of caries lesions with monomeric low-viscosity peptide solutions would be followed by in situ polymerization triggered by conditions of pH and ionic strength, providing a biomimetic scaffold capable of hydroxyapatite nucleation, promoting repair. Our aim was to determine the effect of an anionic peptide applied to caries-like lesions in human dental enamel under simulated intra-oral conditions of pH cycling. Peptide treatment significantly increased net mineral gain by the lesions, due to both increased remineralization and inhibition of demineralization over a five-day period. The assembled peptide was also capable of inducing hydroxyapatite nucleation de novo. The results suggest that self-assembling peptides may be useful in the modulation of mineral behavior during in situ dental tissue engineering.

BACKGROUND: A number of different dental implant designs are currently in clinical use. A successful outcome of implant placement is thought, at least in part, to be due to the primary stability of an implant after placement. Few data are available for comparing the primary stability characteristics of different implant designs. PURPOSE: This investigation compared the primary stability of five types of endosseous dental implant of varying geometry and surface topography. MATERIALS AND METHODS: Comparison was made between a standard threaded commercially pure titanium implant (Nobel Biocare AB, Göteborg, Sweden), the Mark II self-tapping implant (Nobel Biocare AB, Göteborg, Sweden), the Mark IV tapered self-tapping implant (Nobel Biocare AB, Göteborg, Sweden), the Astra Tioblast (AstraTech AB, Mölndahl, Sweden), and the 3i Osseotite (3I [Implant Innovations Incorporated], Palm Beach, Florida, USA). Fifty-two fixtures were placed in the maxillary bone of nine unembalmed human cadavers. Implant stability as a function of peak insertion torque and resonance frequency values was recorded for each fixture site after placement. Removal torque was also measured 1-hour postinsertion. Assessment of bone quality at each site was made. RESULTS: All of the implants tested demonstrated good primary stability in type 2 and 3 bone. The Standard, Mark II, Osseotite, and Tioblast were less stable when placed into bone type 4. The Mark IV implants appeared to maintain a high primary stability even in Type 4 bone. CONCLUSION: When looking across all bone qualities, the Mark IV implant develops a significantly higher insertion torque than the Standard, Mark II, and Osseotite implant types, and a significantly higher resonance frequency value than the Standard implant, indicating a higher interfacial stiffness at the implant-bone interface.

The chemical changes which occur during the process of carious destruction of enamel are complex due to a number of factors. First, substituted hydroxyapatite, the main component of dental enamel, can behave in a very complex manner during dissolution. This is due not only to its ability to accept substituent ions but also to the wide range of calcium phosphate species which can form following dissolution. In addition, the composition, i.e., the extent of substitution, changes throughout enamel in the direction of carious attack, i.e., from surface to interior. Both surface and positively birefringent zones of the lesion clearly illustrate that carious destruction is not simple dissolution. Selective dissolution of soluble minerals occurs, and there is the probability of reprecipitation. The role of fluoride here is crucial in that not only does it protect enamel per se but also its presence in solution means that rather insoluble fluoridated species can form very easily, encouraging redeposition. The role of organic material clearly needs further investigation, but there is the real possibility of both inhibition of repair and facilitation of redeposition. For the future, delivering fluoride deep into the lesion would appear to offer the prospect of improved repair. This would entail a delivery vehicle which solved the problem of fluoride uptake by apatite at the tooth surface. Elucidation of the role of organic material may also reveal putative mechanisms for encouraging repair and/or protecting the enamel mineral.

OBJECTIVES: The purpose of this study was to evaluate the clinical plaque disclosing agent erythrosine as a photosensitizer in the photodynamic killing of the oral bacterium Streptococcus mutans grown as a biofilm. METHODS: S. mutans biofilms of 200 microm thickness were grown in a constant-depth film fermenter. In addition to determining localization of the photosensitizer within biofilms using confocal laser scanning microscopy (CLSM), we compared the bacterial killing efficacy of erythrosine with that of two well-characterized photosensitizers, methylene blue (MB) and photofrin. Incubations were carried out with each photosensitizer (22 microM), and irradiation was for 15 min using a 400 W white light source. RESULTS: The CLSM results showed that erythrosine is taken up into S. mutans biofilms, where it is associated with the biomass of the biofilm rather than the fluid-filled channels and voids. Comparison of the cell killing efficacy of erythrosine in S. mutans biofilms of different ages showed that erythrosine was 1-2 log(10) more effective at killing biofilm bacteria than photofrin and 0.5-1 log(10) more effective than MB. The results were statistically significant (P < 0.01). Photodynamic therapy (PDT) with all three photosensitizers was increasingly effective as biofilm age increased, suggesting that temporal changes in biofilm architecture and composition affect susceptibility to PDT. CONCLUSIONS: PDT using erythrosine as photosensitizer shows excellent potential as a treatment for oral plaque biofilms.

Deep microbial biofilms are a major problem in many industrial, environmental, and medical settings. Novel approaches are needed to understand the structure and metabolism of these biofilms. Two-photon excitation microscopy (TPE) and conventional confocal laser scanning microscopy (CLSM) were compared quantitatively for the ability to visualize bacteria within deep in vitro biofilms. pH gradients within these biofilms were determined by fluorescence lifetime imaging, together with TPE. A constant-depth film fermentor (CDFF) was inoculated for 8 h at 50 ml. h(-1) with a defined mixed culture of 10 species of bacteria grown in continuous culture. Biofilms of fixed depths were developed in the CDFF for 10 or 11 days. The microbial compositions of the biofilms were determined by using viable counts on selective and nonselective agar media; diverse mixed-culture biofilms developed, including aerobic, facultative, and anaerobic species. TPE was able to record images four times deeper than CLSM. Importantly, in contrast to CLSM images, TPE images recorded deep within the biofilm showed no loss of contrast. The pH within the biofilms was measured directly by means of fluorescence lifetime imaging; the fluorescence decay of carboxyfluorescein was correlated with biofilm pH and was used to construct a calibration curve. pH gradients were detectable, in both the lateral and axial directions, in steady-state biofilms. When biofilms were overlaid with 14 mM sucrose for 1 h, distinct pH gradients developed. Microcolonies with pH values of below pH 3.0 were visible, in some cases adjacent to areas with a much higher pH (>5.0). TPE allowed resolution of images at significantly greater depths (as deep as 140 microm) than were possible with CLSM. Fluorescence lifetime imaging allowed the in situ, real-time imaging of pH and the detection of sharp gradients of pH within microbial biofilms.

Streptococcus salivarius is an early colonizer of human oral and nasopharyngeal epithelia, and strain K12 has reported probiotic effects. An emerging paradigm indicates that commensal bacteria downregulate immune responses through the action on NF-kappaB signaling pathways, but additional mechanisms underlying probiotic actions are not well understood. Our objective here was to identify host genes specifically targeted by K12 by comparing their responses with responses elicited by pathogens and to determine if S. salivarius modulates epithelial cell immune responses. RNA was extracted from human bronchial epithelial cells (16HBE14O- cells) cocultured with K12 or bacterial pathogens. cDNA was hybridized to a human 21K oligonucleotide-based array. Data were analyzed using ArrayPipe, InnateDB, PANTHER, and oPOSSUM. Interleukin 8 (IL-8) and growth-regulated oncogene alpha (Groalpha) secretion were determined by enzyme-linked immunosorbent assay. It was demonstrated that S. salivarius K12 specifically altered the expression of 565 host genes, particularly those involved in multiple innate defense pathways, general epithelial cell function and homeostasis, cytoskeletal remodeling, cell development and migration, and signaling pathways. It inhibited baseline IL-8 secretion and IL-8 responses to LL-37, Pseudomonas aeruginosa, and flagellin in epithelial cells and attenuated Groalpha secretion in response to flagellin. Immunosuppression was coincident with the inhibition of activation of the NF-kappaB pathway. Thus, the commensal and probiotic behaviors of S. salivarius K12 are proposed to be due to the organism (i) eliciting no proinflammatory response, (ii) stimulating an anti-inflammatory response, and (iii) modulating genes associated with adhesion to the epithelial layer and homeostasis. S. salivarius K12 might thereby ensure that it is tolerated by the host and maintained on the epithelial surface while actively protecting the host from inflammation and apoptosis induced by pathogens.

PURPOSE: To determine the changes in stability as a reflection of early healing around single-stage, roughened-surface implants in humans utilizing resonance frequency analysis (RFA). RFA makes use of a transducer, attached to an implant, which is excited over a range of sound frequencies with subsequent response analysis. MATERIALS AND METHODS: Twenty patients had 1 to 4 implants placed in the posterior maxilla or mandible. Bone type was classified into 1 of 4 groups according to the Lekholm and Zarb index (1985). RFA was used for direct measurement of implant stability on the day of implant placement and consecutively once per week for 6 weeks and at weeks 8 and 10. RESULTS: Twenty-seven ITI SLA implants placed in the premolar and molar regions of the maxilla and mandible were evaluated. Early failure occurred with 1 implant related to parafunction. The remaining 26 implants were distributed as follows: 29.6% in Type 1 bone, 37% in Type 2 or 3 bone, and 33.3% in Type 4 bone. The lowest mean stability measurement was at 3 weeks for all bone types. The percentage decrease in stability from baseline to 3 weeks was highest for Type 4 bone (8.6%), as was the percentage increase in stability from 3 to 10 weeks (26.9%). A Bonferroni adjusted Student t test comparison of bone groups at each time point revealed highly significant differences between implant stability in Types 1 and 4 bone at 3 weeks (P = .004) and a moderately significant difference between Types 2, 3, and 4 bone (P = .08) at 3 weeks. Implant stability did not change significantly during the 10-week period in Type 1 bone (P > .10). With the same test, by 5 weeks, no bone groups showed any difference in implant RFA measurements (P = 1.0). DISCUSSION: This study demonstrated the lowest values for implant stability at 3 weeks after placement for all bone types. This effect was statistically significant and most pronounced in Type 4 bone. CONCLUSION: There was no significant difference in the pattern of stability changes among different bone types after 5 weeks of healing.

The hydroxyapatite crystals of mature enamel are unusually large, uniform and regularly disposed within the tissue, implying that their development is a highly controlled process. The organic matrix of developing enamel is presumed to play an important role in the modulation of mineral deposition and growth during tooth morphogenesis but the precise functions of individual matrix proteins remain unclear. The aim of this review was to survey the current knowledge of enamel matrix proteins with a view to suggesting possible functions. The organic matrix is highly heterogeneous, comprising proteins derived from a number of different genes, including amelogenin, enamelin, ameloblastin (amelin/sheathlin), tuftelin, dentine sialophosphoprotein, enzymes and serum proteins such as albumin. Each of these classes appears to undergo post-secretory sequential degradation which contributes further towards matrix heterogeneity. Possible functions of these proteins include de novo mineral nucleation/initiation (dentine sialophosphoprotein, tuftelin), mineral ion binding as crystal precursors (amelogenin, enamelin), control of crystal growth (amelogenin, enamelin, ameloblastin), support of growing crystals (amelogenin, enamelin), determination of prismatic structure (ameloblastin), cell signalling (tuftelin, ameloblastin), control of secretion (breakdown products) and protection of the mineral phase (amelogenin, enamelin). Failure of these mechanisms could lead to incomplete maturation of the enamel and the eruption of dysplastic tissue.

BACKGROUND: The host provides environmental conditions that support diverse communities of microorganisms on all environmentally-exposed surfaces of the body. MATERIALS AND METHODS: To review the literature to determine which properties of the host substantially influence the development of dental biofilms. RESULTS: The mouth facilitates the growth of a characteristic resident microbiota. The composition of the oral microbiota is influenced by temperature, pH, and atmosphere, as well as by the host defences and host genetics. In addition, the host supplies endogenous nutrients and a variety of surfaces for biofilm formation. In health, the resident oral microbiota forms a symbiotic relationship with the host, regulated by active host-microbe cross talk. This resident microbiota is sensitive to perturbations in the host environment, especially to changes in nutrient supply and pH, so that previously minor components of the microbiota can become more competitive (and vice versa), resulting in reorganization of biofilm community structure. CONCLUSION: The host environment dictates the composition and gene expression of the resident microbiota. Changes in oral environmental conditions can disrupt the normal symbiotic relationship between the host and its resident microbes, and increase the risk of disease.

Determination of the structure of human plaque will be of great benefit in the prediction of its formation and also the effects of treatment. However, a problem lies in the harvesting of undisturbed intact plaque samples from human volunteers and the viewing of the biofilms in their natural state. In this study, we used an in situ device for the in vivo generation of intact dental plaque biofilms on natural tooth surfaces in human subjects. Two devices were placed in the mouths of each of eight healthy volunteers and left to generate biofilm for 4 days. Immediately upon removal from the mouth, the intact, undisturbed biofilms were imaged by the non-invasive technique of confocal microscopy in both reflected light and fluorescence mode. Depth measurements indicated that the plaque formed in the devices was thicker round the edges at the enamel/nylon junction (range = 75-220 microm) than in the center of the devices (range = 35-215 microm). The reflected-light confocal images showed a heterogeneous structure in all of the plaque biofilms examined; channels and voids were clearly visible. This is in contrast to images generated previously by electron microscopy, suggesting a more compact structure. Staining of the biofilms with fluorescein in conjunction with fluorescence imaging suggested that the voids were fluid-filled. This more open architecture is consistent with recent models of biofilm structure from other habitats and has important implications for the delivery of therapeutics to desired targets within the plaque.

Dental-unit water systems (DUWS) harbor bacterial biofilms, which may serve as a haven for pathogens. The aim of this study was to investigate the microbial load of water from DUWS in general dental practices and the biofouling of DUWS tubing. Water and tube samples were taken from 55 dental surgeries in southwestern England. Contamination was determined by viable counts on environmentally selective, clinically selective, and pathogen-selective media, and biofouling was determined by using microscopic and image analysis techniques. Microbial loading ranged from 500 to 10(5) CFU. ml(-1); in 95% of DUWS water samples, it exceeded European Union drinking water guidelines and in 83% it exceeded American Dental Association DUWS standards. Among visible bacteria, 68% were viable by BacLight staining, but only 5% of this "viable by BacLight" fraction produced colonies on agar plates. Legionella pneumophila, Mycobacterium spp., Candida spp., and Pseudomonas spp. were detected in one, five, two, and nine different surgeries, respectively. Presumptive oral streptococci and Fusobacterium spp. were detected in four and one surgeries, respectively, suggesting back siphonage and failure of antiretraction devices. Hepatitis B virus was never detected. Decontamination strategies (5 of 55 surgeries) significantly reduced biofilm coverage but significantly increased microbial numbers in the water phase (in both cases, P < 0.05). Microbial loads were not significantly different in DUWS fed with soft, hard, deionized, or distilled water or in different DUWS (main, tank, or bottle fed). Microbiologically, no DUWS can be considered "cleaner" than others. DUWS deliver water to patients with microbial levels exceeding those considered safe for drinking water.

The WHO Commission on Social Determinants of Health issued the 2008 report 'Closing the gap within a generation - health equity through action on the social determinants of health' in response to the widening gaps, within and between countries, in income levels, opportunities, life expectancy, health status, and access to health care. Most individuals and societies, irrespective of their philosophical and ideological stance, have limits as to how much unfairness is acceptable. In 2010, WHO published another important report on 'Equity, Social Determinants and Public Health Programmes', with the aim of translating knowledge into concrete, workable actions. Poor oral health was flagged as a severe public health problem. Oral disease and illness remain global problems and widening inequities in oral health status exist among different social groupings between and within countries. The good news is that means are available for breaking poverty and reduce if not eliminate social inequalities in oral health. Whether public health actions are initiated simply depends on the political will. The Ottawa Charter for Health Promotion (1986) and subsequent charters have emphasized the importance of policy for health, healthy environments, healthy lifestyles, and the need for orientation of health services towards health promotion and disease prevention. This report advocates that oral health for all can be promoted effectively by applying this philosophy and some major public health actions are outlined.

Hemodynamic assessment is an integral part of the diagnosis and management of cardiovascular disease. Four-dimensional cardiovascular magnetic resonance flow imaging (4D Flow CMR) allows comprehensive and accurate assessment of flow in a single acquisition. This consensus paper is an update from the 2015 '4D Flow CMR Consensus Statement'. We elaborate on 4D Flow CMR sequence options and imaging considerations. The document aims to assist centers starting out with 4D Flow CMR of the heart and great vessels with advice on acquisition parameters, post-processing workflows and integration into clinical practice. Furthermore, we define minimum quality assurance and validation standards for clinical centers. We also address the challenges faced in quality assurance and validation in the research setting. We also include a checklist for recommended publication standards, specifically for 4D Flow CMR. Finally, we discuss the current limitations and the future of 4D Flow CMR. This updated consensus paper will further facilitate widespread adoption of 4D Flow CMR in the clinical workflow across the globe and aid consistently high-quality publication standards.

This project examined the relative significance of dietary sugars, toothbrushing frequency and social class as predictors of caries experience (caries vs. no caries) among 1,450 British pre-school children who took part in the National Diet and Nutrition Survey. This cross-sectional survey was based on a representative sample of children aged 1.5-4.5 years studied in 1992/3. Children were classified into four groups according to social class and toothbrushing habit. Diet/caries associations were examined for biscuits and cakes, sugar confectionery, chocolate confectionery and soft drinks, and the percentage of energy from non-milk extrinsic sugars, using data on amount and frequency of consumption from 4-day weighed dietary records. In stepwise logistic regressions, the strength of the association between social class and caries experience was twice that between toothbrushing and caries, and nearly three times that between sugar confectionery and caries (other dietary variables were not significant). The association of caries with sugar confectionery (both in amount and frequency) was only present among children whose teeth were brushed less than twice a day. Toothbrushing frequency appeared to have a stronger impact on caries prevention in non-manual compared with manual children. Household expenditure on confectionery was associated with caries only among children from the manual group. The findings suggest the hypothesis that regular brushing (twice a day) with a fluoride toothpaste may have greater impact on caries in young children than restricting sugary foods.