Cost-effectiveness analysis of using probiotics, prebiotics, or synbiotics to control Campylobacter in broilers.

Campylobacter is a food safety hazard, which causes a substantial human disease burden. Infected broiler meat is a common source of campylobacteriosis. The use of probiotics, prebiotics, or synbiotics has been associated with controlling Campylobacter infections in broilers, although efficacy remains a contentiously debated issue. On-farm use of probiotics, prebiotics, or synbiotics is gaining momentum. Therefore, it is interesting to analyze the economic viability of this potential intervention to reduce Campylobacter prevalence in broilers. A normative cost-effectiveness analysis was conducted to estimate the cost-effectiveness ratio of using probiotics, prebiotics, or synbiotics in broiler production in Denmark, the Netherlands, Poland, and Spain. The cost-effectiveness ratio was defined as the estimated costs of probiotics, prebiotics, or synbiotics use divided by the estimated public health benefits expressed in euro (€) per avoided disability-adjusted life year (DALY). The model considered differences between the countries in zootechnical and economic farm performance, in import, export, and transit of live broilers, broiler meat and meat products, and in disease burden of Campylobacter-related human illness. Simulation results revealed that the costs per avoided DALY were lowest in Poland and Spain (€4,000-€30,000 per avoided DALY) and highest in the Netherlands and Denmark (€70,000-€340,000 per avoided DALY) at an efficacy ranging from 10 to 20%. In Poland and Spain, using probiotics can be classified as a moderately expensive intervention if efficacy is more than 10%, otherwise it is relatively expensive. In the Netherlands and Denmark, using probiotics is a relatively expensive intervention irrespective of efficacy. However, if probiotics, prebiotics, or synbiotics were assumed to enhance broiler performance, it would become a relatively cost-effective intervention for Campylobacter even at low efficacy levels of 1 to 10%.

Assessing the sustainability of egg production systems in The Netherlands.

Housing systems for laying hens have changed over the years due to increased public concern regarding animal welfare. In terms of sustainability, animal welfare is just one aspect that needs to be considered. Social aspects as well as environmental and economic factors need to be included as well. In this study, we assessed the sustainability of enriched cage, barn, free-range, and organic egg production systems following a predefined protocol. Indicators were selected within the social, environmental, and economic dimensions, after which parameter values and sustainability limits were set for the core indicators in order to quantify sustainability. Uncertainty in the parameter values as well as assigned weights and compensabilities of the indicators influenced the outcome of the sustainability assessment. Using equal weights for the indicators showed that, for the Dutch situation, enriched cage egg production was most sustainable, having the highest score on the environmental dimension, whereas free-range egg production gave the highest score in the social dimension (covering food safety, animal welfare, and human welfare). In the economic dimension both enriched cage egg and organic egg production had the highest sustainability score. When weights were attributed according to stakeholder outputs, individual differences were seen, but the overall scores were comparable to the sustainability scores based on equal weights. The provided method enabled a quantification of sustainability using input from stakeholders to include societal preferences in the overall assessment. Allowing for different weights and compensabilities helps policymakers in communicating with stakeholders involved and provides a weighted decision regarding future housing systems for laying hens.

The anti-viral effect of sorafenib in hepatitis C-related hepatocellular carcinoma.

BACKGROUND: Sorafenib is currently the only approved systemic therapy shown to have efficacy in the treatment of advanced hepatocellular carcinoma (HCC). Recent studies suggest that hepatitis C (HCV)-related HCC patients derive more clinical benefit from sorafenib than other subgroups, but the mechanism for this effect is unknown. In vitro data suggest that sorafenib may exert anti-viral properties, and thus our aim in this study was to evaluate potential anti-viral activity of sorafenib in patients with HCV-related HCC. AIM: To evaluate potential anti-viral activity of sorafenib in patients with HCV-related HCC. METHODS: We prospectively enrolled patients with HCV-related HCC treated with sorafenib for up to 6 months. Baseline clinical, viral and oncologic data were collected. Patients' HCV viral loads were obtained at various time points, and compared with their baseline viral levels. No patients received any known anti-viral therapy during this time. RESULTS: Thirty-three patients were identified with baseline and subsequent HCV levels available for analysis. Six patients completed 6 months of full dose sorafenib, and comparisons of their HCV viral loads showed no significant change at week 24 (difference of means = 0.3500, CI: -0.1799-0.8799, P = 0.150), or the interim time points. Similarly, the HCV viral loads of all patients who received sorafenib and the viral loads of those patients who had tumour response to sorafenib showed no significant changes at any time point. CONCLUSION: Despite preclinical data and previous subgroup analyses suggesting that sorafenib has an anti-viral effect against HCV, this study suggests that sorafenib lacks significant anti-viral activity in HCV patients with HCC.

Olympic outreach: testing for sexually transmitted infections in construction workers.

Concerns have been voiced in the national press that the surge in migrant construction workers leading up to the 2012 Olympics Games would increase the levels of sexual ill health in East London. Between 2009 and 2011, we sent a sexual health outreach team to the Olympic Park and Village. A total of 614 clients were tested, of whom 91% were men and 46% reported English/Scottish/Welsh ethnicity. The age range was 17-73 years and median age 30 years. Reported sexual risk factors were low, including use of commercial sex workers. Prevalence of sexually transmitted infections was low, with Chlamydia trachomatis found in 20 clients (3%), and hepatitis B diagnosed in one client. This study, although small, did not support the image of construction workers presenting a higher than average sexual health risk.

Amyloid beta and impairment in multiple memory systems in older transgenic APP TgCRND8 mice.

The relationship between amyloid beta and cognitive dysfunction in mouse models of Alzheimer's disease has been evaluated predominantly with the spatial reference memory version of the water maze task. However, as Alzheimer's disease encompasses decline in multiple memory systems, it is important to also utilize non-spatial tasks to fully characterize the role of amyloid on behaviour in animal models. We used the TgCRND8 mouse model of Alzheimer's disease to evaluate the effect of amyloid on spatial reference memory, as well as on the non-spatial task of acquisition of conditioned taste aversion, and on the procedural task of swimming to a visible platform. We demonstrate that 8- to 12-month-old TgCRND8 mice are significantly impaired in all three tasks, and that the levels of soluble amyloid beta are significantly correlated with impairment in spatial reference memory, but not with impairment in conditioned taste aversion or swimming to a visible platform. Insoluble fractions of amyloid, which correspond closely to amyloid plaque burden in the brain, are not associated with any behavioural measure. Our study extends the characterization of the model to stages of advanced amyloid pathology and demonstrates that older TgCRND8 mice are impaired in multiple memory systems, including procedural tasks, which are spared at younger ages. The lack of association between amyloid plaques and memory decline supports clinical findings in Alzheimer's patients.

Increasing children's physical activity: a peer modelling, rewards and pedometer-based intervention.

BACKGROUND/OBJECTIVES: To evaluate a peer modelling, rewards and pedometer-feedback intervention designed to increase children's physical activity and which uses the same behaviour-change principles underlying the Food Dude Healthy Eating Programme. SUBJECTS/METHODS: The study was conducted in two primary schools in Wales. Participants were 47 children (21 boys, 26 girls) from the experimental school and 53 children (29 boys, 24 girls) from a matched control school, aged 9-11 years. Children in the experimental school took part in the intervention; over 8 days they were introduced to fictional role models (the Fit n' Fun Dudes) via visual and audio intervention materials and received small rewards when their daily pedometer step counts increased by 1500 steps per day relative to their baselines. Pedometer measures were taken from children in both schools at baseline, intervention (baseline 2 for the control school) and 12-week follow-up. RESULTS: Among experimental girls, steps per day were significantly higher during the intervention (14 686+/-2540) and at follow-up (13 737+/-3288) compared to baseline (10 864+/-2481, P<0.001) and control girls (P<0.005). Experimental boys showed significantly higher daily steps during the intervention compared to baseline (16 237+/-4204 cf. 13 452+/-3258, P<0.001) and control boys (P<0.005). There were no significant differences between activity levels of experimental and control boys at follow-up. CONCLUSIONS: The intervention resulted in substantial increases in children's physical activity, which was well maintained over a 12-week period in girls.

Increasing parental provision and children's consumption of lunchbox fruit and vegetables in Ireland: the Food Dudes intervention.

BACKGROUND/OBJECTIVES: Previous research in the United Kingdom, where there is a school canteen system, has shown that the Food Dudes intervention substantially increases children's fruit and vegetable consumption. The current study evaluated its effectiveness in Ireland where school meals are not provided and children bring food to school in lunchboxes. SUBJECTS/METHODS: Participants were 4- to 11-year-old children attending two primary schools; the schools were randomly assigned to experimental or control conditions (n=228 and 207, respectively). During the 16-day intervention in the experimental school, children watched video adventures featuring the heroic Food Dudes, and received small rewards for eating fruit and vegetables provided. In both schools, parental provision and children's consumption of fruit and vegetables in the lunchboxes were assessed at baseline and 12-month follow-up (Lunchbox measures). Fruit and vegetables were provided in both schools over an 8-day baseline phase and the 16-day intervention, and children's consumption was measured (school-provided food measures). RESULTS: Relative to baseline, consumption of the school-provided foods increased during the intervention in the experimental school (P<0.001), whereas in the control school it showed a significant decline. At 12-month follow-up, parents in the experimental school provided and their children consumed significantly more lunchbox fruit, vegetables and juice relative to baseline and to the control school (P<0.001 in all instances). CONCLUSIONS: The Food Dudes intervention was effective in changing parental provision and children's consumption of lunchbox fruit and vegetables in Ireland.

Alloreactive (CD4-Independent) CD8+ T cells jeopardize long-term survival of intrahepatic islet allografts.

Despite success of early islet allograft engraftment and survival in humans, late islet allograft loss has emerged as an important clinical problem. CD8+ T cells that are independent of CD4+ T cell help can damage allograft tissues and are resistant to conventional immunosuppressive therapies. Previous work demonstrates that islet allografts do not primarily initiate rejection by the (CD4-independent) CD8-dependent pathway. This study was performed to determine if activation of alloreactive CD4-independent, CD8+ T cells, by exogenous stimuli, can precipitate late loss of islet allografts. Recipients were induced to accept intrahepatic islet allografts (islet 'acceptors') by short-term immunotherapy with donor-specific transfusion (DST) and anti-CD154 mAb. Following the establishment of stable long-term islet allograft function for 60-90 days, recipients were challenged with donor-matched hepatocellular allografts, which are known to activate (CD4-independent) CD8+ T cells. Allogeneic islets engrafted long-term were vulnerable to damage when challenged locally with donor-matched hepatocytes. Islet allograft loss was due to allospecific immune damage, which was CD8- but not CD4-dependent. Selection of specific immunotherapy to suppress both CD4- and CD8-dependent immune pathways at the time of transplant protects islet allografts from both early and late immune damage.

Activation and maturation of alloreactive CD4-independent, CD8 cytolytic T cells.

The goal of this study was to determine the in vivo conditions that promote activation of the (CD4-independent) CD8+ T cell-mediated rejection pathway. We have previously noted that hepatocellular but not islet allografts readily activate this rejection pathway. In the current study, we utilized these two cell transplant models to investigate whether differences in host cell recruitment to the graft site, expression of T-cell activation markers by CD8+ graft infiltrating cells (GICs), and/or development of delayed-type hypersensitivity (DTH) and cytotoxic T lymphocyte cell-mediated effector functions could account for the differential transplant outcomes. The collective results demonstrate that recruitment of CD8+ T cells to the site of transplant, CD103 or CD69 expression on CD8+ GICs, and activation of alloreactive DTH responses are insufficient to initiate CD4-independent, CD8-dependent transplant rejection. Instead, rejection by alloreactive (CD4-independent) CD8+ T cells correlated with expression of CD25, CD154 and CD43 by CD8+ GICs, in vitro alloproliferation by recipient CD8+ T cells, and the development of in vivo allospecific cytolytic effector function. These results suggest that tissue-derived factors influence the activation and maturation of (CD4-independent) CD8+ T cells into cytolytic effectors, which correlates with transplant rejection.

Increasing children's fruit and vegetable consumption: a peer-modelling and rewards-based intervention.

OBJECTIVE: To evaluate a peer-modelling and rewards-based intervention designed to increase children's fruit and vegetable consumption. DESIGN: Over a 5-month period, children in an experimental and a control school were presented with fruit and vegetables at lunchtime. Children aged 5-7 y also received fruit at snacktime (mid-morning). The intervention was implemented in the experimental school and levels of fruit and vegetable consumption were measured at baseline, intervention and at 4-month follow-up. SETTING: Two inner-city London primary schools. SUBJECTS: In total, 749 children aged 5-11 y. INTERVENTION: Over 16 days children watched video adventures featuring heroic peers (the Food Dudes) who enjoy eating fruit and vegetables, and received small rewards for eating these foods themselves. After 16 days there were no videos and the rewards became more intermittent. MAIN OUTCOME MEASURES: Consumption was measured (i) at lunchtime using a five-point observation scale; (ii) at snacktime using a weighed measure; (iii) at home using parental recall. RESULTS: Compared to the control school, lunchtime consumption in the experimental school was substantially higher at intervention and follow-up than baseline (P<0.001), while snacktime consumption was higher at intervention than baseline (P<0.001). The lunchtime data showed particularly large increases among those who initially ate very little. There were also significant increases in fruit and vegetable consumption at home (P<0.05). CONCLUSIONS: The intervention was effective in bringing about substantial increases in children's consumption of fruit and vegetables.

Effects of a peer modelling and rewards-based intervention to increase fruit and vegetable consumption in children.

OBJECTIVE: To measure children's consumption of, and liking for, fruit and vegetables and how these are altered by a peer modelling and rewards-based intervention. DESIGN: In this initial evaluation of the programme, children's consumption of fruit and vegetables were compared within and across baseline and intervention phases. SETTING: Three primary schools in England and Wales. SUBJECTS: In total, 402 children, aged from 4 to 11 y. INTERVENTION: Over 16 days, children watched six video adventures featuring heroic peers (the Food Dudes) who enjoy eating fruit and vegetables, and received small rewards for eating these foods themselves. MAIN OUTCOME MEASURES: Fruit and vegetable consumption was measured (i) in school at lunchtime and snacktime using a five-point observation scale, with inter-rated reliability and weighed validation tests; and (ii) at home using parental recall. A questionnaire measured children's liking for fruit and vegetables before and after the intervention. RESULTS: Consumption during the intervention was significantly higher than during baseline at lunchtime and at snacktime (P<0.001 in all instances). Consumption outside school was significantly higher during the intervention on weekdays (P<0.05) but not weekend days. Following the intervention, children's liking for fruit and vegetables also showed a significant increase (P<0.001). CONCLUSIONS: The peer modelling and rewards-based intervention was shown to be effective in bringing about substantial increases in children's consumption of, and expressed liking for, fruit and vegetables. SPONSORSHIP: : Horticultural Development Council, Fresh Produce Consortium, ASDA, Co-operative Group, Safeway, Sainsbury, Somerfield, Tesco and Birds Eye Wall's.

First evidence of enterobiasis in ancient Egypt.

The oldest and most common parasite for which we have direct evidence, in the New World, is Enterobius vernicularis. Numerous archaeological sites, especially in the arid American southwest, have yielded fecal samples positive for pinworm ova, some of these dating back 10,000 yr. Reports of pinworm from the Old World are scarce. This article reports the first evidence of pinworm infection from Roman-occupied (30 BC-AD 395) Egypt.

Therapeutically effective antibodies against amyloid-beta peptide target amyloid-beta residues 4-10 and inhibit cytotoxicity and fibrillogenesis.

Immunization of transgenic mouse models of Alzheimer disease using amyloid-beta peptide (Abeta) reduces both the Alzheimer disease-like neuropathology and the spatial memory impairments of these mice. However, a therapeutic trial of immunization with Abeta42 in humans was discontinued because a few patients developed significant meningo-encephalitic cellular inflammatory reactions. Here we show that beneficial effects in mice arise from antibodies selectively directed against residues 4-10 of Abeta42, and that these antibodies inhibit both Abeta fibrillogenesis and cytotoxicity without eliciting an inflammatory response. These findings provide the basis for improved immunization antigens as well as attempts to design small-molecule mimics as alternative therapies.

Assembly of Alzheimer's amyloid-beta fibrils and approaches for therapeutic intervention.

Amyloid plaques are the principal features of Alzheimers disease (AD) pathology and are considered to be a major factor in the disease process. These fibrillar deposits are composed primarily of the 40-42 residue amyloid-beta (Abeta) peptide which is a proteolytic product of a larger membrane precursor protein. Electron microscopy and X-ray diffraction have revealed that the mature amyloid fibrils are assembled as a highly beta-sheet polymer that has a well-defined protofilament quaternary structure. This organization is observed for amyloid fibrils from a wide variety of disorders and appears to represent a structural superfamily. Amyloid plaques also contain a number of other components such as proteoglycans that contain highly sulfated glycosaminoglycan (GAG) chains. These amyloid-associated elements may contribute to the aggregation and/or stabilization of Abeta as insoluble fibrils. We have recently developed an aggressive model for Abeta plaque formation in transgenic mice that exhibits an "early-onset" phenotype. Immunocytochemistry has demonstrated that even with this rapid progression, Abeta deposits within the neuropil and cerebrovascular system all co-localize with heparan sulfate proteoglycans (HSPG). These findings indicate a number of structural features that can be targeted as potential sites for the development of amyloid inhibitors. In addition, the use of small compounds that interfere with the proteoglycan-amyloid pathway may be effective therapeutic agents that can be assessed through the use of these transgenic models.

Early-onset amyloid deposition and cognitive deficits in transgenic mice expressing a double mutant form of amyloid precursor protein 695.

We have created early-onset transgenic (Tg) models by exploiting the synergistic effects of familial Alzheimer's disease mutations on amyloid beta-peptide (Abeta) biogenesis. TgCRND8 mice encode a double mutant form of amyloid precursor protein 695 (KM670/671NL+V717F) under the control of the PrP gene promoter. Thioflavine S-positive Abeta amyloid deposits are present at 3 months, with dense-cored plaques and neuritic pathology evident from 5 months of age. TgCRND8 mice exhibit 3,200-4,600 pmol of Abeta42 per g brain at age 6 months, with an excess of Abeta42 over Abeta40. High level production of the pathogenic Abeta42 form of Abeta peptide was associated with an early impairment in TgCRND8 mice in acquisition and learning reversal in the reference memory version of the Morris water maze, present by 3 months of age. Notably, learning impairment in young mice was offset by immunization against Abeta42 (Janus, C., Pearson, J., McLaurin, J., Mathews, P. M., Jiang, Y., Schmidt, S. D., Chishti, M. A., Horne, P., Heslin, D., French, J., Mount, H. T. J., Nixon, R. A., Mercken, M., Bergeron, C., Fraser, P. E., St. George-Hyslop, P., and Westaway, D. (2000) Nature 408, 979-982). Amyloid deposition in TgCRND8 mice was enhanced by the expression of presenilin 1 transgenes including familial Alzheimer's disease mutations; for mice also expressing a M146L+L286V presenilin 1 transgene, amyloid deposits were apparent by 1 month of age. The Tg mice described here suggest a potential to investigate aspects of Alzheimer's disease pathogenesis, prophylaxis, and therapy within short time frames.

Costs of immunization registries: experiences from the All Kids Count II Projects.

BACKGROUND: Immunization registries are tools to improve and sustain immunization coverage rates for our nation's preschool children. Developing a means of supporting registries over the long term requires information on costs to operate registries. METHODS: To determine the annual cost per child to operate immunization registries for the 16 All Kids Count (AKC) II projects, some of the most developed registry projects in the United States, we projected a national figure for operating registries and compared the figure with a variety of potential cost offsets. RESULTS: When the registries are fully operational, the average cost per child for the 16 AKC II projects will be $3.91 (range, $1.60 to $6.23; interquartile range, $2.91 to $4.81) per year. CONCLUSIONS: Based on the AKC study, maintaining a nationwide network of registries for children aged 0 to 5 will require an estimated $78.2 million. Cost offsets include not having to manually retrieve records for school entry, child care, change in provider, and Health Plan Employer Data Information Set reports; not having to carry out the National Immunization Survey; and prevention of overimmunization. We estimate these offsets at $113.8 million annually.

Partial remediation of speaker and listener behaviors in people with severe dementia.

We investigated the effects of contingent reinforcement (Intervention 1) and contingent reinforcement with modeling (Intervention 2) on speaker and listener behaviors in 5 people with severe dementia. Intervention 1 generally increased listener behavior; there was no clear effect on tacting, but echoic behavior increased in the one case investigated. Given the weak baseline repertoires of these clients and the paucity of other effective interventions, even the small increases in verbal behaviors found here are important. Further gains may be achieved, for example, if reinforcement opportunity per trial type were to be increased from one to several per day or if participants were trained to echo the listener stimulus in mand compliance tasks.