A cost-effectiveness analysis of community water fluoridation for schoolchildren.

BACKGROUND: Community water fluoridation (CWF), the controlled addition of fluoride to the water supply for the prevention of dental caries (tooth decay), is considered a safe and effective public health intervention. The Republic of Ireland (Ireland) is the only country in Europe with a legislative mandate for the fluoridation of the public water supply, a key component of its oral health policy. However, more recently, there has been an increase in public concern around the relevance of the intervention given the current environment of multiple fluoride sources and a reported increase in the prevalence of enamel fluorosis. The aim of this economic analysis is to provide evidence to inform policy decisions on whether the continued public investment in community water fluoridation remains justified under these altered circumstances. METHODS: Following traditional methods of economic evaluation and using epidemiological data from a representative sample of 5-, 8-, and 12-year-old schoolchildren, this cost-effectiveness analysis, conducted from the health-payer perspective, compared the incremental costs and consequences associated with the CWF intervention to no intervention for schoolchildren living in Ireland in 2017. A probabilistic model was developed to simulate the potential lifetime treatment savings associated with the schoolchildren's exposure to the intervention for one year. RESULTS: In 2017, approximately 71% of people living in Ireland had access to a publicly provided fluoridated water supply at an average per capita cost to the state of €2.15. The total cost of CWF provision to 5-, 8-, and 12-year-old schoolchildren (n = 148,910) was estimated at €320,664, and the incremental cost per decayed, missing, or filled tooth (d3vcmft/D3vcMFT) prevented was calculated at €14.09. The potential annual lifetime treatment savings associated with caries prevented for this cohort was estimated at €2.95 million. When the potential treatment savings were included in the analysis, the incremental cost per d3vcmft/D3vcMFT prevented was -€115.67, representing a cost-saving to the health-payer and a positive return on investment. The results of the analysis were robust to both deterministic and probability sensitivity analyses. CONCLUSION: Despite current access to numerous fluoride sources and a reported increase in the prevalence of enamel fluorosis, CWF remains a cost-effective public health intervention for Irish schoolchildren.

Partial volume correction for improved PET quantification in 18F-NaF imaging of atherosclerotic plaques.

BACKGROUND: Accurate quantification of plaque imaging using 18F-NaF PET requires partial volume correction (PVC). METHODS: PVC of PET data was implemented by the use of a local projection (LP) method. LP-based PVC was evaluated with an image quality (NEMA) and with a thorax phantom with "plaque-type" lesions of 18-36 mL. The validated PVC method was then applied to a cohort of 17 patients, each with at least one plaque in the carotid or ascending aortic arteries. In total, 51 calcified (HU > 110) and 16 non-calcified plaque lesions (HU < 110) were analyzed. The lesion-to-background ratio (LBR) and the relative change of LBR (ΔLBR) were measured on PET. RESULTS: Following PVC, LBR of the spheres (NEMA phantom) was within 10% of the original values. LBR of the thoracic lesions increased by 155% to 440% when the LP-PVC method was applied to the PET images. In patients, PVC increased the LBR in both calcified [mean = 78% (-8% to 227%)] and non-calcified plaques [mean = 41%, (-9%-104%)]. CONCLUSIONS: PVC helps to improve LBR of plaque-type lesions in both phantom studies and clinical patients. Better results were obtained when the PVC method was applied to images reconstructed with point spread function modeling.

Bone-marrow-homing lipid nanoparticles for genome editing in diseased and malignant haematopoietic stem cells.

Therapeutic genome editing of haematopoietic stem cells (HSCs) would provide long-lasting treatments for multiple diseases. However, the in vivo delivery of genetic medicines to HSCs remains challenging, especially in diseased and malignant settings. Here we report on a series of bone-marrow-homing lipid nanoparticles that deliver mRNA to a broad group of at least 14 unique cell types in the bone marrow, including healthy and diseased HSCs, leukaemic stem cells, B cells, T cells, macrophages and leukaemia cells. CRISPR/Cas and base editing is achieved in a mouse model expressing human sickle cell disease phenotypes for potential foetal haemoglobin reactivation and conversion from sickle to non-sickle alleles. Bone-marrow-homing lipid nanoparticles were also able to achieve Cre-recombinase-mediated genetic deletion in bone-marrow-engrafted leukaemic stem cells and leukaemia cells. We show evidence that diverse cell types in the bone marrow niche can be edited using bone-marrow-homing lipid nanoparticles.

In vivo editing of lung stem cells for durable gene correction in mice.

In vivo genome correction holds promise for generating durable disease cures; yet, effective stem cell editing remains challenging. In this work, we demonstrate that optimized lung-targeting lipid nanoparticles (LNPs) enable high levels of genome editing in stem cells, yielding durable responses. Intravenously administered gene-editing LNPs in activatable tdTomato mice achieved >70% lung stem cell editing, sustaining tdTomato expression in >80% of lung epithelial cells for 660 days. Addressing cystic fibrosis (CF), NG-ABE8e messenger RNA (mRNA)-sgR553X LNPs mediated >95% cystic fibrosis transmembrane conductance regulator (CFTR) DNA correction, restored CFTR function in primary patient-derived bronchial epithelial cells equivalent to Trikafta for F508del, corrected intestinal organoids and corrected R553X nonsense mutations in 50% of lung stem cells in CF mice. These findings introduce LNP-enabled tissue stem cell editing for disease-modifying genome correction.

Severe cleidocranial dysplasia and hypophosphatasia in a child with microdeletion of the C-terminal region of RUNX2.

Cleidocranial dysplasia (CCD) is a rare autosomal dominant skeletal dysplasia due to mutations causing haploinsufficiency of RUNX2, an osteoblast transcription factor specific for bone and cartilage. The classic form of CCD is characterized by delayed closure of the fontanels, hypoplastic or aplastic clavicles and dental anomalies. Clinical reports suggest that a subset of patients with CCD have skeletal changes which mimic hypophosphatasia (HPP). Mutations in RUNX2 are detected in approximately 65% of cases of CCD, and microdeletions occur in 13%. We present clinical and radiological features in a 6-year-old child with severe CCD manifested by absence of the clavicles marked calvarial hypomineralization, osteoporosis and progressive kyphoscoliosis. HPP features included Bowdler spurs, severe osteopenia, and low alkaline phosphatase. Following negative mutation analysis of RUNX2, comparative genomic hybridization (CGH) microarray was performed. The result revealed a microdeletion in RUNX2, disrupting the C-terminal part of the gene.

A four year longitudinal sero-epidemiological study of bovine herpesvirus type-1 (BHV-1) in adult cattle in 107 unvaccinated herds in south west England.

BACKGROUND: Bovine herpesvirus type-1 (BHV-1) is an important pathogen of cattle that presents with a variety of clinical signs, including the upper respiratory tract infection infectious bovine rhinotracheitis (IBR). A seroepidemiological study of BHV-1 antibodies was conducted in England from 2002 - 2004: 29,782 blood samples were taken from 15,736 cattle from 114 herds which were visited on up to three occasions. Antibody concentration was measured using a commercial ELISA. Farm management information was collected using an interview questionnaire, and herd size and cattle movements were obtained from the cattle tuberculosis testing database and the British Cattle Movement Service. Hierarchical statistical models were used to investigate associations between cattle and herd variables and the continuous outcome percentage positive (PP) values from the ELISA test in unvaccinated herds. RESULTS: There were 7 vaccinated herds, all with at least one seropositive bovine. In unvaccinated herds 83.2% had at least one BHV-1 seropositive bovine, and the mean cattle and herd BHV-1 seroprevalence were 42.5% and 43.1% respectively. There were positive associations between PP value, age, herd size, presence of dairy cattle. Adult cattle in herds with grower cattle had lower PP values than those in herds without grower cattle. Purchased cattle had significantly lower PP values than homebred cattle, whereas cattle in herds that were totally restocked after the foot-and-mouth epidemic in 2001 had significantly higher PP values than those in continuously stocked herds. Samples taken in spring and summer had significantly lower PP values than those taken in winter, whereas those taken in autumn had significantly higher PP values than those taken in winter. The risks estimated from a logistic regression model with a binary outcome (seropositive yes/no) were similar. CONCLUSION: The prevalence of BHV-1 seropositivity in cattle and herds has increased since the 1970s. Although the study population prevalence of BHV-1 was temporally stable during study period, the associations between serological status and cattle age, herd size, herd type, presence of young stock and restocked versus continuously stocked herds indicate that there is heterogeneity between herds and so potential for further spread of BHV-1 within and between herds.

Adsorption of metallic radionuclides on plastic phantom walls.

Metal radionuclide solutions at neutral pH adhere to plastic containers. Adsorption of radionuclides on the walls of phantoms leads to a nonuniform activity distribution, which could adversely affect imaging studies, as well as phantom-based validations of absorbed dose calculations used in radioimmunotherapy, requiring accurate knowledge of the underlying activity distribution. In the work reported here, the authors determined the degree of metal chelation required to minimize metallic radionuclide oxide formation and adsorption on phantom walls in order to yield more reliable experimental data for validating image-based dosimetry. Using hollow spherical plastic phantoms, the authors evaluated three different radionuclides, I-131, In-111, and Y-90, in solutions containing three different concentrations of the chelator, ethylenediaminetetraacetate (EDTA). Adsorption to plastic walls was determined using microSPECT imaging and/or by counting aliquots of solutions. Reconstructed images and measurements of I-131 activity showed that it was uniformly distributed within all spheres; however, images of In-111 in 0.25-microM EDTA indicated that the activity concentration near the wall was much higher than that in the middle of the sphere. The decrease in activity concentration near the center of the spheres was approximately 47%. Y-90 in 0.25-microM EDTA behaved similarly; the activity concentration of Y-90 decreased by 46%. For an In-111 or Y-90 radioactivity concentration of 0.74 MBq/mL, a 2.5-microM EDTA solution was required to achieve a uniform distribution, suggesting that, under our experimental conditions, approximately 700 EDTA molecules were required for each radiometal atom to prevent precipitation and adsorption on poly(methylmethacrylate). For certain radiometals, e.g., In-111 or Y-90, adequate chelation is essential to achieve uniform activity concentration values and homogeneous distribution within the phantom compartments.

A four year longitudinal sero-epidemiology study of Neospora caninum in adult cattle from 114 cattle herds in south west England: associations with age, herd and dam-offspring pairs.

BACKGROUND: Neosporosis caused by the protozoan parasite Neospora caninum, is an economically important cause of abortion, stillbirth, low milk yield, reduced weight gain and premature culling in cattle. Consequently, a seroepidemiological study of N. caninum antibodies was conducted in England with 29,782 samples of blood taken from 15,736 cattle from 114 herds visited on three occasions at yearly intervals. Herds were categorised into lower (< 10%) and higher (> or = 10%) median herd seroprevalence. Hierarchical models were run to investigate associations between the sample to positive (S/P) ratio and herd and cattle factors. RESULTS: Ninety-four percent of herds had at least one seropositive cow; 12.9% of adult cattle had at least one seropositive test. Approximately 90% of herds were seropositive at all visits; 9 herds (8%) changed serological status between visits. The median N. caninum seroprevalence in positive herds was 10% (range 0.4% to 58.8%). There was a positive association between the serostatus of offspring and dams that were ever seropositive. In the hierarchical model of low seroprevalence herds there was no significant association between S/P ratio and cattle age. There was a significantly lower S/P ratio in cattle in herds that were totally restocked after the foot-and-mouth epidemic of 2001 compared with those from continuously stocked herds and cattle purchased into these herds had a higher S/P ratio than homebred cattle. In the model of high seroprevalence herds the S/P ratio increased with cattle age, but was not associated with restocking or cattle origin. CONCLUSION: There were no strong temporal changes in herd seroprevalence of N. caninum but 90% of herds had some seropositive cattle over this time period. Vertical transmission from seropositive dams appeared to occur in all herds. In herds with a high seroprevalence the increasing S/P ratio in 2-4 year old cattle is suggestive of exposure to N. caninum: horizontal transmission between adult cattle, infection from a local source or recrudescence and abortions. Between-herd movements of infected cattle enhance the spread of N. caninum, particularly into low seroprevalence herds. Some restocked herds had little exposure to N. caninum, while in others infection had spread in the time since restocking.

Highly effective yet simple transmembrane anion transporters based upon ortho-phenylenediamine bis-ureas.

Simple, highly fluorinated receptors are shown to function as highly effective transmembrane anion antiporters with the most active transporters rivalling the transport efficacy of natural anion transporter prodigiosin for bicarbonate.

Mammary analog secretory carcinoma of salivary glands: a report of 2 cases in the lips.

OBJECTIVE: This study presents 2 cases of labial mammary analog secretory carcinoma (MASC) including diagnostic criteria and a review of literature. MASC has not been previously described in the dental literature. DESIGN: Two cases of MASC and 1 case of acinic cell carcinoma (ACC) of the lips were reviewed for their microscopic and immunohistochemical features. Fluorescence in situ hybridization (FISH) for the ETV6-NTRK3 translocation was performed. The clinical features of 65 cases previously described in the medical literature are reviewed. RESULTS: MASCs had hematoxylin and eosin features similar to those of ACC but demonstrated larger, globular periodic acid-Schiff positive deposits, whereas ACC had finer granular deposits. MASCs were strongly positive for S100, vimentin, and mammaglobin, whereas ACC was negative for S100 and vimentin and only focally mammaglobin positive. FISH demonstrated that MASCs were positive for ETV6 disruption. CONCLUSION: MASCs are newly described, can occur in a wide age range, favor males, and can be misinterpreted as ACC or adenocarcinoma not otherwise specified by routine microscopy.

A synergistic approach to anion antiport.

A synergistic approach to Cl(-)/HCO(3)(-) antiport has been demonstrated in POPC lipid bilayers using an ion selective electrode assay showing that, when using combinations of carriers each optimised for a particular component of the transport process, enhanced rates of transport are observed.

Tripodal transmembrane transporters for bicarbonate.

Easy-to-make tripodal tris-thiourea receptors based upon tris(2-aminoethyl)amine are capable of chloride/bicarbonate transport and as such represent a new class of bicarbonate transport agent.

The recovery of latent fingermarks and DNA using a silicone-based casting material.

There are many techniques available for the recovery of fingermarks at scenes of crime including the possibility of taking casts of the marks. Casts can be advantageous in cases where other destructive recovery techniques might not be suitable, such as when recovering finger marks deposited on valued or immobile items. In this research, Isomark (a silicone-based casting material) was used to recover casts of finger marks placed on a variety of substrates. Casts were enhanced using cyanoacrylate fuming. Good quality marks were successfully recovered from a range of smooth, non-porous surfaces. Recovery from semi-porous surfaces was shown to be inefficient. DNA was subsequently extracted from the casts using QIAamp Mini extraction kits, amplified and profiled. Full DNA profiles were obtained 34% of samples extracted.

Recovery of DNA and fingerprints from touched documents.

This study investigated the various factors affecting DNA profiling from DNA recovered from fingerprints deposited on paper before and after fingerprint enhancement treatments. The DNeasy plant mini kit (QIAGEN) was found to improve DNA recovery from paper by over 150% compared with the QIAamp mini kit. A significant decrease in the amount of DNA recovered was observed following treatment with DFO and/or Ninhydrin. This decrease in yield did not have a comparably significant effect on the quality of the SGM Plus profiles. Furthermore, this study found that whilst certain paper types, such as newspaper, magazine and filter paper allowed for the good recovery of DNA, common office paper and white card, strongly interfered with the recovery of DNA resulting in poor quality profiles.