Improving Child Oral Health: Cost Analysis of a National Nursery Toothbrushing Programme

Dental caries is one of the most common diseases of childhood. The aim of this study was to compare the cost of providing the Scotland-wide nursery toothbrushing programme with associated National Health Service (NHS) cost savings from improvements in the dental health of five-year-old children: through avoided dental extractions, fillings and potential treatments for decay.

Methods

Estimated costs of the nursery toothbrushing programme in 2011/12 were requested from all Scottish Health Boards. Unit costs of a filled, extracted and decayed primary tooth were calculated using verifiable sources of information. Total costs associated with dental treatments were estimated for the period from 1999/00 to 2009/10. These costs were based on the unit costs above and using the data of the National Dental Inspection Programme and then extrapolated to the population level. Expected cost savings were calculated for each of the subsequent years in comparison with the 2001/02 dental treatment costs. Population standardised analysis of hypothetical cohorts of 1000 children per deprivation category was performed.

Results

The estimated cost of the nursery toothbrushing programme in Scotland was £1,762,621 per year. The estimated cost of dental treatments in the baseline year 2001/02 was £8,766,297, while in 2009/10 it was £4,035,200. In 2002/03 the costs of dental treatments increased by £213,380 (2.4%). In the following years the costs decreased dramatically with the estimated annual savings ranging from £1,217,255 in 2003/04 (13.9% of costs in 2001/02) to £4,731,097 in 2009/10 (54.0%). Population standardised analysis by deprivation groups showed that the largest decrease in modelled costs was for the most deprived cohort of children.

Conclusions

The NHS costs associated with the dental treatments for five-year-old children decreased over time. In the eighth year of the toothbrushing programme the expected savings were more than two and a half times the costs of the programme implementation.     

Risk Factors for Maternal Mortality in Rural Tigray,Northern Ethiopia: A Case-Control Study

Background

Maternal mortality continues to have devastating impacts in many societies, where it constitutes a leading cause of death, and thus remains a core issue in international development. Nevertheless, individual determinants of maternal mortality are often unclear and subject to local variation. This study aims to characterise individual risk factors for maternal mortality in Tigray, Ethiopia.

Methods

A community-based case-control study was conducted, with 62 cases and 248 controls from six randomly-selected rural districts. All maternal deaths between May 2012 and September 2013 were recruited as cases and a random sample of mothers who delivered in the same communities within the same time period were taken as controls. Multiple logistic regression was used to identify independent determinants of maternal mortality.

Results

Four independent individual risk factors, significantly associated with maternal death, emerged. Women who were not members of the voluntary Women’s Development Army were more likely to experience maternal death (OR 2.07, 95% CI 1.04–4.11), as were women whose husbands or partners had below-median scores for involvement during pregnancy (OR 2.19, 95% CI 1.14–4.18). Women with a pre-existing history of other illness were also at increased risk (OR 5.58, 95% CI 2.17–14.30), as were those who had never used contraceptives (OR 2.58, 95% CI 1.37–4.85). Previous pregnancy complications, a below-median number of antenatal care visits and a woman’s lack of involvement in health care decision making were significant bivariable risks that were not significant in the multivariable model.

Conclusions

The findings suggest that interventions aimed at reducing maternal mortality need to focus on encouraging membership of the Women’s Development Army, enhancing husbands’ involvement in maternal health services, improving linkages between maternity care and other disease-specific programmes and ensuring that women with previous illnesses or non-users of contraceptive services are identified and followed-up as being at increased risk during pregnancy and childbirth.     

Anthropogenically-Mediated Density Dependence in a Declining Farmland Bird

Land management intrinsically influences the distribution of animals and can consequently alter the potential for density-dependent processes to act within populations. For declining species, high densities of breeding territories are typically considered to represent productive populations. However, as density-dependent effects of food limitation or predator pressure may occur (especially when species are dependent upon separate nesting and foraging habitats), high territory density may limit per-capita productivity. Here, we use a declining but widespread European farmland bird, the yellowhammer Emberiza citrinella L., as a model system to test whether higher territory densities result in lower fledging success, parental provisioning rates or nestling growth rates compared to lower densities. Organic landscapes held higher territory densities, but nests on organic farms fledged fewer nestlings, translating to a 5 times higher rate of population shrinkage on organic farms compared to conventional. In addition, when parental provisioning behaviour was not restricted by predation risk (i.e., at times of low corvid activity), nestling provisioning rates were higher at lower territory densities, resulting in a much greater increase in nestling mass in low density areas, suggesting that food limitation occurred at high densities. These findings in turn suggest an ecological trap, whereby preferred nesting habitat does not provide sufficient food for rearing nestlings at high population density, creating a population sink. Habitat management for farmland birds should focus not simply on creating a high nesting density, but also on ensuring heterogeneous habitats to provide food resources in close proximity to nesting birds, even if this occurs through potentially restricting overall nest density but increasing population-level breeding success.     

miRNA-197 and miRNA-223 Predict Cardiovascular Death in a Cohort of Patients with Symptomatic Coronary Artery Disease

Background

Circulating microRNAs (miRNAs) have been described as potential diagnostic biomarkers in cardiovascular disease and in particular, coronary artery disease (CAD). Few studies were undertaken to perform analyses with regard to risk stratification of future cardiovascular events. miR-126, miR-197 and miR-223 are involved in endovascular inflammation and platelet activation and have been described as biomarkers in the diagnosis of CAD. They were identified in a prospective study in relation to future myocardial infarction.

Objectives

The aim of our study was to further evaluate the prognostic value of these miRNAs in a large prospective cohort of patients with documented CAD.

Methods

Levels of miR-126, miR-197 and miR-223 were evaluated in serum samples of 873 CAD patients with respect to the endpoint cardiovascular death. miRNA quantification was performed using real time polymerase chain reaction (RT-qPCR).

Results

The median follow-up period was 4 years (IQR 2.78–5.04). The median age of all patients was 64 years (IQR 57–69) with 80.2% males. 38.9% of the patients presented with acute coronary syndrome (ACS), 61.1% were diagnosed with stable angina pectoris (SAP). Elevated levels of miRNA-197 and miRNA-223 reliably predicted future cardiovascular death in the overall group (miRNA-197: hazard ratio (HR) 1.77 per one standard deviation (SD) increase (95% confidence interval (CI) 1.20; 2.60), p = 0.004, C-index 0.78; miRNA-223: HR 2.23 per one SD increase (1.20; 4.14), p = 0.011, C-index 0.80). In ACS patients the prognostic power of both miRNAs was even higher (miRNA-197: HR 2.24 per one SD increase (1.25; 4.01), p = 0.006, C-index 0.89); miRA-223: HR 4.94 per one SD increase (1.42; 17.20), p = 0.012, C-index 0.89).

Conclusion

Serum-derived circulating miRNA-197 and miRNA-223 were identified as predictors for cardiovascular death in a large patient cohort with CAD. These results reinforce the assumption that circulating miRNAs are promising biomarkers with prognostic value with respect to future cardiovascular events.     

Functionality of Dengue Virus Specific Memory T Cell Responses in Individuals Who Were Hospitalized or Who Had Mild or Subclinical Dengue Infection

Background

Although antibody responses to dengue virus (DENV) in naturally infected individuals have been extensively studied, the functionality of DENV specific memory T cell responses in relation to clinical disease severity is incompletely understood.

Methodology/Principal findings

Using ex vivo IFNγ ELISpot assays, and by determining cytokines produced in ELISpot supernatants, we investigated the functionality of DENV-specific memory T cell responses in a large cohort of individuals from Sri Lanka (n=338), who were naturally infected and were either hospitalized due to dengue or had mild or sub clinical dengue infection. We found that T cells of individuals with both past mild or sub clinical dengue infection and who were hospitalized produced multiple cytokines when stimulated with DENV-NS3 peptides. However, while DENV-NS3 specific T cells of those with mild/sub clinical dengue infection were more likely to produce only granzyme B (p=0.02), those who were hospitalized were more likely to produce both TNFα and IFNγ (p=0.03) or TNFα alone.We have also investigated the usefulness of a novel T cell based assay, which can be used to determine the past infecting DENV serotype. 92.4% of DENV seropositive individuals responded to at least one DENV serotype of this assay and none of the seronegatives responded. Individuals who were seronegative, but had received the Japanese encephalitis vaccine too made no responses, suggesting that the peptides used in this assay did not cross react with the Japanese encephalitis virus.

Conclusions/significance

The types of cytokines produced by DENV-specific memory T cells appear to influence the outcome of clinical disease severity. The novel T cell based assay, is likely to be useful in determining the past infecting DENV serotype in immune-epidemiological studies and also in dengue vaccine trials.     

Diversity in host clone performance within a Chinese hamster ovary cell line

Much effort has been expended to improve the capabilities of individual Chinese hamster ovary (CHO) host cell lines to synthesize recombinant therapeutic proteins (rPs). However, given the increasing variety in rP molecular types and formats it may be advantageous to employ a toolbox of CHO host cell lines in biomanufacturing. Such a toolbox would contain a panel of hosts with specific capabilities to synthesize certain molecular types at high volumetric concentrations and with the correct product quality (PQ). In this work, we examine a panel of clonally derived host cell lines isolated from CHOK1SV for the ability to manufacture two model proteins, an IgG4 monoclonal antibody (Mab) and an Fc‐fusion protein (etanercept). We show that these host cell lines vary in their relative ability to synthesize these proteins in transient and stable pool production format. Furthermore, we examined the PQ attributes of the stable pool‐produced Mab and etanercept (by N‐glycan ultra performance liquid chromatography (UPLC) and liquid chromatography ‐ tandem mass spectrometry (LC‐MS/MS), respectively), and uncovered substantial variation between the host cell lines in Mab N‐glycan micro‐heterogeneity and etanercept N and O‐linked macro‐heterogeneity. To further investigate the capabilities of these hosts to act as cell factories, we examined the glycosylation pathway gene expression profiles as well as the levels of endoplasmic reticulum (ER) and mitochondria in the untransfected hosts. We uncovered a moderate correlation between ER mass and the volumetric product concentration in transient and stable pool Mab production. This work demonstrates the utility of leveraging diversity within the CHOK1SV pool to identify new host cell lines with different performance characteristics. © 2015 American Institute of Chemical Engineers Biotechnol. Prog., 31:1187–1200, 2015     

Vaccination with Human Papillomavirus Pseudovirus-Encapsidated Plasmids Targeted to Skin Using Microneedles

Human papilloma virus-like particles (HPV VLP) serve as the basis of the current licensed vaccines for HPV. We have previously shown that encapsidation of DNA expressing the model antigen M/M2 from respiratory syncytial virus (RSV) in HPV pseudovirions (PsV) is immunogenic when delivered intravaginally. Because the HPV capsids confer tropism for basal epithelium, they represent attractive carriers for vaccination targeted to the skin using microneedles. In this study we asked: 1) whether HPV16 VLP administered by microneedles could induce protective immune responses to HPV16 and 2) whether HPV16 PsV-encapsidated plasmids delivered by microneedles could elicit immune responses to both HPV and the antigen delivered by the transgene. Mice immunized with HPV16 VLP coated microneedles generated robust neutralizing antibody responses and were protected from HPV16 challenge. Microneedle arrays coated with HPV16-M/M2 or HPV16-F protein (genes of RSV) were then tested and dose-dependent HPV and F-specific antibody responses were detected post-immunization, and M/M2-specific T-cell responses were detected post RSV challenge, respectively. HPV16 PsV-F immunized mice were fully protected from challenge with HPV16 PsV and had reduced RSV viral load in lung and nose upon intranasal RSV challenge. In summary, HPV16 PsV-encapsidated DNA delivered by microneedles induced neutralizing antibody responses against HPV and primed for antibody and T-cell responses to RSV antigens encoded by the encapsidated plasmids. Although the immunogenicity of the DNA component was just above the dose response threshold, the HPV-specific immunity was robust. Taken together, these data suggest microneedle delivery of lyophilized HPV PsV could provide a practical, thermostable combined vaccine approach that could be developed for clinical evaluation.     

Insect-Inspired Navigation Algorithm for an Aerial Agent Using Satellite Imagery

Humans have long marveled at the ability of animals to navigate swiftly, accurately, and across long distances. Many mechanisms have been proposed for how animals acquire, store, and retrace learned routes, yet many of these hypotheses appear incongruent with behavioral observations and the animals’ neural constraints. The “Navigation by Scene Familiarity Hypothesis” proposed originally for insect navigation offers an elegantly simple solution for retracing previously experienced routes without the need for complex neural architectures and memory retrieval mechanisms. This hypothesis proposes that an animal can return to a target location by simply moving toward the most familiar scene at any given point. Proof of concept simulations have used computer-generated ant’s-eye views of the world, but here we test the ability of scene familiarity algorithms to navigate training routes across satellite images extracted from Google Maps. We find that Google satellite images are so rich in visual information that familiarity algorithms can be used to retrace even tortuous routes with low-resolution sensors. We discuss the implications of these findings not only for animal navigation but also for the potential development of visual augmentation systems and robot guidance algorithms.     

Pretransplant HRCT Characteristics Are Associated with Worse Outcome of Lung Transplantation for Cystic Fibrosis Patients

Objectives

Peri- and postoperative complications diminish the outcome of lung transplantation (LTx) in patients with cystic fibrosis (CF). We hypothesized that the degree of pathological findings on pre-LTx high resolution computed tomography (HRCT) is associated with higher morbidity and mortality in CF.

Methods

All our CF patients undergoing LTx between 2001 and 2011 were included. HRCT examinations were evaluated according to a scoring system for pulmonary disease in CF patients, the Severe Advanced Lung Disease (SALD) score and for pleural involvement.

Results

Fifty-three patients were included. Dominant infectious/inflammatory disease according to the SALD score was observed in 10 patients (19%). Five (50%) of those patients died within one week after LTx, compared to 2 (5%) patients without dominant infectious/inflammatory disease (p<0.001). This difference in survival percentage remained also significant in multivariate analysis. Patients with infectious/inflammatory disease received more packed red blood cells; 26 versus 8 in the first week (p<0.001). Pleural thickening was associated with higher requirement (10 units) for blood transfusion during LTx, compared to patients with normal pleura (4 units).

Conclusions

The analysis of HRCT in CF patients according to the SALD score showed that dominant infectious/inflammatory disease is associated with a higher mortality after LTx. If confirmed in other studies, HRCT might aid estimation of surgical risk in some adult CF patients.