Direct costs of glaucoma and severity of the disease:A multinational long term study of resource utilisation in Europe

Background: Resource utilisation and direct costs associated with glaucoma progression in Europe are unknown. As population progressively ages, the economic impact of the disease will increase. Methods: From a total of 1655 consecutive cases, the records of 194 patients were selected and stratified by disease severity. Record selection was based on diagnoses of primary open angle glaucoma, glaucoma suspect, ocular hypertension, or normal tension glaucoma; 5 years minimum follow up were required. Glaucoma severity was assessed using a six stage glaucoma staging system based on static threshold visual field parameters. Resource utilisation data were abstracted from the charts and unit costs were applied to estimate direct costs to the payer. Resource utilisation and estimated direct cost of treatment, per person year, were calculated. Results: A statistically significant increasing linear trend (p = 0.018) in direct cost as disease severity worsened was demonstrated. The direct cost of treatment increased by an estimated €86 for each incremental step ranging from €455 per person year for stage 0 to €969 per person year for stage 4 disease. Medication costs ranged from 42% to 56% of total direct cost for all stages of disease. Conclusions: These results demonstrate for the first time in Europe that resource utilisation and direct medical costs of glaucoma management increase with worsening disease severity. Based on these findings, managing glaucoma and effectively delaying disease progression would be expected to significantly reduce the economic burden of this disease. These data are relevant to general practitioners and healthcare administrators who have a direct influence on the distribution of resources.

Combination of CFD and DOE to analyse solid particle erosion in elbows

Solid particle erosion is a major concern in the engineering industry, particularly where transport of slurry flow is involved. Such flow regimes are characteristic of those in alumina refinement plants. The entrainment of particulate matter, for example sand, in the Bayer liquor can cause severe erosion in pipe fittings, especially in those which redirect the flow. The considerable costs involved in the maintenance and replacement of these eroded components led to an interest in research into erosion prediction by numerical methods at Rusal Aughinish alumina refinery, Limerick, Ireland, and the University of Limerick. The first stage of this study focused on the use of computational fluid dynamics (CFD) to simulate solid particle erosion in elbows. Subsequently an analysis of the factors that affect erosion of elbows was performed using design of experiments (DOE) techniques. Combining CFD with DOE harnesses the computational power of CFD in the most efficient manner for prediction of elbow erosion. An analysis of the factors that affect the erosion of elbows was undertaken with the intention of producing an erosion prediction model. © 2009 Taylor & Francis.

Role of nitric oxide in maintenance of basal oral tissue blood flow in anesthetized cats

Experiments were undertaken to determine if nitric oxide (NO) plays a role in regulation of basal blood flow in the oral cavity of pentobarbital anesthetized cats and, if so, to quantify this effect using dose-response relationships. Blood flow was continuously measured from the surface of the tongue and mandibular gingiva (laser-Doppler flowmetry) and from the lingual artery (ultrasonic flowmetry). Cardiovascular parameters also were recorded. Administration of the nonselective inhibitor of nitric oxide synthase (NOS), L-NAME (0.08-20 mg/kg i.v.), produced a dose-related increase of blood pressure associated with decreases of blood flow at all three measurement sites. Maximal blood flow depression of 50-60% was seen 30-60 min after administration of 1.25 mg/kg of L-NAME. D-NAME (1.25 mg/kg i.v.) was inactive at all sites. Subsequent administration of L-arginine partially reversed effects of L-NAME in the lingual artery and tongue, but not in the gingival circulation. The neuronally selective NOS inhibitor, 7-nitroindazole (7-NI, 30 mg/kg i.p.), was devoid of effect on any of the measured parameters. These results suggest that endothelial (but not neuronally derived) NO plays an important role in control of basal blood flow in oral tissues of the cat.

Description and predictors of hospital costs of oesophageal cancer during the first year following diagnosis in Northern Ireland

The cost-effectiveness of novel interventions in the treatment of cancer is well researched; however, relatively little attention is paid to the cost of many aspects of routine care. Oesophageal cancer is the ninth most common cancer in the UK and sixth most common cause of cancer death. It usually presents late and has a poor prognosis. The hospital costs incurred by oesophageal cancer patients diagnosed in Northern Ireland in 2005 (n = 198) were determined by review of medical records. The average cost of hospital care per patient in the 12 months from presentation was £7847. Variations in total hospital costs by age at diagnosis, gender, cancer stage, histological type, mortality at 1 year, co-morbidity count and socio-economic status were analysed using multiple regression analyses. Higher costs were associated with earlier stages of cancer and cancer stage remained a significant predictor of costs after controlling for cancer type, patient age and mortality at 1 year. Thus, although early detection of cancer usually improves survival, this would mean increased costs in the first year. Deprivation achieved borderline significance with those from more deprived areas having lower resource consumption relative to the more affluent. © 2013 John Wiley & Sons Ltd.

PTEN Phosphatase-Independent Maintenance of Glandular Morphology in a Predictive Colorectal Cancer Model System

Organotypic models may provide mechanistic insight into colorectal cancer (CRC) morphology. Three-dimensional (3D) colorectal gland formation is regulated by phosphatase and tensin homologue deleted on chromosome 10 (PTEN) coupling of cell division cycle 42 (cdc42) to atypical protein kinase C (aPKC). This study investigated PTEN phosphatase-dependent and phosphatase-independent morphogenic functions in 3D models and assessed translational relevance in human studies. Isogenic PTEN-expressing or PTEN-deficient 3D colorectal cultures were used. In translational studies, apical aPKC activity readout was assessed against apical membrane (AM) orientation and gland morphology in 3D models and human CRC. We found that catalytically active or inactive PTEN constructs containing an intact C2 domain enhanced cdc42 activity, whereas mutants of the C2 domain calcium binding region 3 membrane-binding loop (M-CBR3) were ineffective. The isolated PTEN C2 domain (C2) accumulated in membrane fractions, but C2 M-CBR3 remained in cytosol. Transfection of C2 but not C2 M-CBR3 rescued defective AM orientation and 3D morphogenesis of PTEN-deficient Caco-2 cultures. The signal intensity of apical phospho-aPKC correlated with that of Na/H exchanger regulatory factor-1 (NHERF-1) in the 3D model. Apical NHERF-1 intensity thus provided readout of apical aPKC activity and associated with glandular morphology in the model system and human colon. Low apical NHERF-1 intensity in CRC associated with disruption of glandular architecture, high cancer grade, and metastatic dissemination. We conclude that the membrane-binding function of the catalytically inert PTEN C2 domain influences cdc42/aPKC-dependent AM dynamics and gland formation in a highly relevant 3D CRC morphogenesis model system.

Identification of a BRCA1-mRNA Splicing Complex Required for Efficient DNA Repair and Maintenance of Genomic Stability

Mutations within BRCA1 predispose carriers to a high risk of breast and ovarian cancers. BRCA1 functions to maintain genomic stability through the assembly of multiple protein complexes involved in DNA repair, cell-cycle arrest, and transcriptional regulation. Here, we report the identification of a DNA damage-induced BRCA1 protein complex containing BCLAF1 and other key components of the mRNA-splicing machinery. In response to DNA damage, this complex regulates pre-mRNA splicing of a number of genes involved in DNA damage signaling and repair, thereby promoting the stability of these transcripts/proteins. Further, we show that abrogation of this complex results in sensitivity to DNA damage, defective DNA repair, and genomic instability. Interestingly, mutations in a number of proteins found within this complex have been identified in numerous cancer types. These data suggest that regulation of splicing by the BRCA1-mRNA splicing complex plays an important role in the cellular response to DNA damage.

Trade-offs between personal immunity and reproduction in the burying beetle, Nicrophorus vespilloides

How are resources split between caring for offspring and self-maintenance? Is the timing of immune challenge important? In burying beetles challenging the immune system prior to breeding does not affect the total number and quality of offspring produced during the individual's lifetime. However, the immune system is suppressed during breeding and if an immune challenge is presented during this time the beetle will upregulate its immune system, but at the detriment to the number of offspring produced during that breeding opportunity.We know that parental investment and immune investment are costly processes, but it is unclear which trait will be prioritized when both may be required. Here, we address this question using the burying beetle Nicrophorus vespilloides, carrion breeders that exhibit biparental care of young. Our results show that immunosuppression occurs during provision of parental care. We measured phenoloxidase (PO) on Days 1-8 of the breeding bout and results show a clear decrease in PO immediately from presentation of the breeding resource onward. Having established baseline immune investment during breeding we then manipulated immune investment at different times by applying a wounding challenge. Beetles were wounded prior to and during the parental care period and reproductive investment quantified. Different effects on reproductive output occur depending on the timing of wounding. Challenging the immune system with wounding prior to breeding does not affect reproductive output and subsequent lifetime reproductive success (LRS). LRS is also unaffected by applying an immune elicitor prior to breeding, though different arms of the immune system are up/downregulated, perhaps indicating a trade-off between cellular and humoral immunity. In contrast, wounding during breeding reduces reproductive output and to the greatest extent if the challenge is applied early in the breeding bout. Despite being immunosuppressed, breeding beetles can still respond to wounding by increasing PO, albeit not to prebreeding levels. This upregulation of PO during breeding may affect parental investment, resulting in a reduction in reproductive output. The potential role of juvenile hormone in controlling this trade-off is discussed.

The lifetime direct cost of periodontal treatment:A case study from a norwegian specialist practice

Background: Successful periodontal treatment requires a commitment to regular lifelong maintenance and may be perceived by patients to be costly. This study calculates the total lifetime cost of periodontal treatment in the setting of a specialist periodontal practice and investigates the cost implications of choosing not to proceed with such treatment. Methods: Data from patients treated in a specialist practice in Norway were used to calculate the total lifetime cost of periodontal treatment that included baseline periodontal treatment, regular maintenance, retreatment, and replacing teeth lost during maintenance. Incremental costs for alternative strategies based on opting to forego periodontal treatment or maintenance and to replace any teeth lost with either bridgework or implants were calculated. Results: Patients who completed baseline periodontal treatment but did not have any additional maintenance or retreatment could replace only three teeth with bridgework or two teeth with implants before the cost of replacing additional teeth would exceed the cost of lifetime periodontal treatment. Patients who did not have any periodontal treatment could replace ≤4 teeth with bridgework or implants before a replacement strategy became more expensive. Conclusions: Within the limits of the assumptions made, periodontal treatment in a Norwegian specialist periodontal practice is cost-effective when compared to an approach that relies on opting to replace teeth lost as a result of progressive periodontitis with fixed restorations. In particular, patients who have initial comprehensive periodontal treatment but do not subsequently comply with maintenance could, on average, replace ≤3 teeth with bridgework or two teeth with implants before this approach would exceed the direct cost of lifetime periodontal treatment in the setting of the specialist practice studied. © 2012 American Academy of Periodontology.

Incorporating Severity and Risk as Factors to the Fardal Cost-Effectiveness Model to Create a Cost-Benefit Model for Periodontal Treatment

Background: A previously described economic model was based on average values for patients diagnosed with chronic periodontitis (CP). However, tooth loss varies among treated patients and factors for tooth loss include CP severity and risk. The model was refined to incorporate CP severity and risk to determine the cost of treating a specific level of CP severity and risk that is associated with the benefit of tooth preservation.

Methods: A population that received and another that did not receive periodontal treatment were used to determine treatment costs and tooth loss. The number of teeth preserved was the difference of the number of teeth lost between the two populations. The cost of periodontal treatment was divided by the number of teeth preserved for combinations of CP severity and risk.

Results: The cost of periodontal treatment divided by the number of teeth preserved ranged from (US) $ 1,405 to $ 4,895 for high or moderate risk combined with any severity of CP and was more than $ 8,639 for low risk combined with mild CP. The cost of a three-unit bridge was $ 3,416, and the cost of a single-tooth replacement was $ 4,787.

Conclusion: Periodontal treatment could be justified on the sole basis of tooth preservation when CP risk is moderate or high regardless of disease severity.

Energy balance of SRC willow used for managing farmyard washings - how does it compare to a conventional wastewater treatment works?

The water and wastewater industry in the UK accounts for around 3% of total energy use and just over 1% of total UK greenhouse gas emissions. Targets for greenhouse gas emissions reduction and higher renewable energy penetration, coupled with rising energy costs, growing demand for wastewater services and tightening EU water quality requirements, have led to an increased interest in alternative wastewater treatment methods. The use of short rotation coppice (SRC) willow for the treatment of wastewater effluent is one such alternative, which brings with it the dual benefits of wastewater treatment and production of biomass for energy. In order to assess the effectiveness of SRC willow, it is important to analyse the overall energy balance in terms of energy input versus energy output. This paper carries out an energy life cycle analysis of a specific SRC willow plantation in Northern Ireland to which farmyard washings (dirty water) are applied. The system boundaries include the establishment, maintenance, and harvesting of the plantation, along with the transport and drying of the wood for biomass combustion. The analysis shows that the overall energy balance is positive, and that the direct and indirect energy demands are 12% and 8% of gross energy production respectively. The energy demands of the plantation are compared with the energy required to treat an equivalent nutrient load in a conventional wastewater treatment plant. While a conventional plant consumes 2.6 MJ/m3 , the irrigation system consumes 1.6 MJ/m3 and the net energy production of the scenario is 48 MJ/m3 .

Prediction of integral type failures in semiconductor manufacturing through classification methods

Smart management of maintenances has become fundamental in manufacturing environments in order to decrease downtime and costs associated with failures. Predictive Maintenance (PdM) systems based on Machine Learning (ML) techniques have the possibility with low added costs of drastically decrease failures-related expenses; given the increase of availability of data and capabilities of ML tools, PdM systems are becoming really popular, especially in semiconductor manufacturing. A PdM module based on Classification methods is presented here for the prediction of integral type faults that are related to machine usage and stress of equipment parts. The module has been applied to an important class of semiconductor processes, ion-implantation, for the prediction of ion-source tungsten filament breaks. The PdM has been tested on a real production dataset. © 2013 IEEE.