Nanocolloidal albumin-IRDye 800CW: a near-infrared fluorescent tracer with optimal retention in the sentinel lymph node

Purpose: At present, the only approved fluorescent tracer for clinical near-infrared fluorescence-guided sentinel node (SN) detection is indocyanine green (ICG), but the use of this tracer is limited due to its poor retention in the SN resulting in the detection of higher tier nodes. We describe the development and characterization of a next-generation fluorescent tracer, nanocolloidal albumin-IRDye 800CW that has optimal properties for clinical SN detection Methods: The fluorescent dye IRDye 800CW was covalently coupled to colloidal human serum albumin (HSA) particles present in the labelling kit Nanocoll in a manner compliant with current Good Manufacturing Practice. Characterization of nanocolloidal albumin-IRDye 800CW included determination of conjugation efficiency, purity, stability and particle size. Quantum yield was determined in serum and compared to that of ICG. For in vivo evaluation a lymphogenic metastatic tumour model in rabbits was used. Fluorescence imaging was performed directly after peritumoral injection of nanocolloidal albumin-IRDye 800CW or the reference ICG/HSA (i.e. ICG mixed with HSA), and was repeated after 24 h, after which fluorescent lymph nodes were excised. Results: Conjugation of IRDye 800CW to nanocolloidal albumin was always about 50% efficient and resulted in a stable and pure product without affecting the particle size of the nanocolloidal albumin. The quantum yield of nanocolloidal albumin-IRDye 800CW was similar to that of ICG. In vivo evaluation revealed noninvasive detection of the SN within 5 min of injection of either nanocolloidal albumin-IRDye 800CW or ICG/HSA. No decrease in the fluorescence signal from SN was observed 24 h after injection of the nanocolloidal albumin-IRDye 800CW, while a strong decrease or complete disappearance of the fluorescence signal was seen 24 h after injection of ICG/HSA. Fluorescence-guided SN biopsy was very easy. Conclusion: Nanocolloidal albumin-IRDye 800CW is a promising fluorescent tracer with optimal kinetic features for SN detection. © The Author(s) 2012

Prospective study of the primary evaluation of 1016 horses with clinical signs of abdominal pain by veterinary practitioners, and the differentiation of critical and non‑critical cases

Background: The majority of research on the evaluation of horses with colic is focused on referral hospital populations. Early identification of critical cases is important to optimise outcome and welfare. The aim of this prospective study was to survey the primary evaluation of horses with clinical signs of abdominal pain by veterinary practitioners, and compare the initial presentation of critical and non-critical cases. Results: Data from 1016 primary evaluations of horses presenting with clinical signs of colic were submitted by 167 veterinary practitioners across the United Kingdom over a 13 month period. The mean age of the study population was 13.5 years (median 12.0, range 0–42). Mean heart rate on primary presentation was 47 beats/min (median 44, range 18–125), mean respiratory rate was 20 breaths/min (median 16, range 6–100), and median gastrointestinal auscultation score (0–12, minimum–maximum) was 5 (range 0–12). Clinical signs assessed using a behavioural severity score (0–17, minimum–maximum), were between 0 and 6 in 70.4 % of cases, and 7 12 for 29.6 % of cases. Rectal examination was performed in 73.8 % of cases. Cases that responded positively to simple medical treatment were categorised retrospectively as ‘non-critical’; cases that required intensive medical treatment, surgical intervention, died or were euthanased were categorised as ‘critical’. Eight-hundred-and-twenty- two cases met these criteria; 76.4 % were ‘non-critical’ and 23.6 % were ‘critical’. Multivariable logistic regression was used to identify features of the clinical presentation associated with critical cases. Five variables were retained in the final multivariable model: combined pain score: (OR 1.19, P 2.5 s (OR 3.21, P = 0.046, 95 % CI 1.023–10.09), weak pulse character (OR 2.90, P = 0.004, 95 % CI 1.39–5.99) and absence of gut sounds in ≥1 quadrant (OR 3.65, P < 0.001, 95 % CI 2.08–6.41). Conclusions: This is the first study comparing the primary presentation of critical and non-critical cases of abdominal pain. Pain, heart rate, gastrointestinal borborygmi and simple indicators of hypovolaemia were significant indicators of critical cases, even at the primary veterinary examination, and should be considered essential components of the initial assessment and triage of horses presenting with colic

A comprehensive evaluation of food fortification with folic acid for the primary prevention of neural tube defects

BACKGROUND: Periconceptional use of vitamin supplements containing folic acid reduces the risk of a neural tube defect (NTD). In November 1998, food fortification with folic acid was mandated in Canada, as a public health strategy to increase the folic acid intake of all women of childbearing age. We undertook a comprehensive population based study in Newfoundland to assess the benefits and possible adverse effects of this intervention. METHODS: This study was carried out in women aged 19–44 years and in seniors from November 1997 to March 1998, and from November 2000 to March 2001. The evaluation was comprised of four components: I) Determination of rates of NTDs; II) Dietary assessment; III) Blood analysis; IV) Assessment of knowledge and use of folic acid supplements. RESULTS: The annual rates of NTDs in Newfoundland varied greatly between 1976 and 1997, with a mean rate of 3.40 per 1,000 births. There was no significant change in the average rates between 1991–93 and 1994–97 (relative risk [RR] 1.01, 95% confidence interval [CI] 0.76–1.34). The rates of NTDs fell by 78% (95% CI 65%–86%) after the implementation of folic acid fortification, from an average of 4.36 per 1,000 births during 1991–1997 to 0.96 per 1,000 births during 1998–2001 (RR 0.22, 95% CI 0.14–0.35). The average dietary intake of folic acid due to fortification was 70 μg/day in women aged 19–44 years and 74 μg/day in seniors. There were significant increases in serum and RBC folate levels for women and seniors after mandatory fortification. Among seniors, there were no significant changes in indices typical of vitamin B(12 )deficiencies, and no evidence of improved folate status masking haematological manifestations of vitamin B(12 )deficiency. The proportion of women aged 19–44 years taking a vitamin supplement containing folic acid increased from 17% to 28%. CONCLUSIONS: Based on these findings, mandatory food fortification in Canada should continue at the current levels. Public education regarding folic acid supplement use by women of childbearing age should also continue

Optimal Afforestation Contracts with Asymmetric Information on Private Environmental Benefits

We investigate the problem of subsidising afforestation when private information exists with respect to the level of private utility derived from the project. We develop a simple model that allows for an intelligent design of contracts when information is asymmetric. The model involves the Principal and two groups of agents (landowners): a green' group deriving high private utility from the projects and a conventional' group deriving lower utility. Afforestation projects may be produced in different environmental quality, and we distinguish between two cases, a high quality and a low quality project. We find that the optimal set of contracts under asymmetric information involves two different contracts. One in which green landowners are somewhat overcompensated for projects of high quality, and one where conventional landowners are offered contracts including lower quality projects, compared to the symmetric case, but with compensation equal to his indifference payment. It is the ability to reduce quality requirements along with subsidies offered that allows for revelation of the private information. Finally, we discus how the results obtained may be used in the implementation of incentive schemes

The Socio-Economic Value of Natural Riverbanks in the Netherlands

Ecologists and economists both use a different approach to determine the value of nature. Its ecological value can be measured using criteria like rarity and diversity of species in an ecosystem. The economic value can be determined using non-market valuation techniques. This paper focuses on an empirical application of the Contingent Valuation Method (CVM) to find out whether this valuation method is a suitable method to estimate the economic value of natural riverbanks in the Netherlands. Natural riverbanks will provide habitat for species that particularly depend on the land water transit area. Since common riverbanks do not provide this habitat, natural river banks increase biodiversity in the Netherlands. On the basis of technical and ecological characteristics nine different types of natural riverbanks were distinguished. For each type a laymen description was made. This description served as a basis for economic valuation by means of CVM. The results of the CVM study shows that the average willingness to pay for non-use of a natural riverbank varied between 16 and 25 Dutch guilders per household year. The willingness to pay for recreational use ranged from 1,07 to 2,50 guilders per visit. The generated outcomes proved to be consistent with results from other studies. At first sight, the economic value of natural riverbanks seemed to be higher than their construction and maintenance cost

On Coalition Formation with Heterogeneous Agents

We propose a framework to analyze coalition formation with heterogeneous agents. Existing literature defines stability conditions that do not ensure that, once an agent decides to sign an agreement, the enlarged coalition is feasible. Defining the concepts of refraction and exchanging, we set up conditions of existence and enlargement of a coalition with heterogeneous agents. We use the concept of exchanging agents to give necessary conditions for internal stability and show that refraction is a sufficient condition for the failure of an enlargement of the coalition. With heterogeneous agents we can get a situation where a group of members of an unstable coalition does not deviate, neither within the coalition nor within the extended coalition. Hence, the possibilities of agreement are richer than in the standard analysis with homogeneous agents. Examples of industrial economics are used for illustration, and an application to climate change negotiations is discussed in more detail

Assessing the Effectiveness of Tradable Landuse Rights for Biodiversity Conservation: An Application to Canada's Boreal Mixedwood Forest

Ecological reserve networks are an important strategy for conserving biodiversity. One approach to selecting reserves is to use optimization algorithms that maximize an ecological objective function subject to a total reserve area constraint. Under this approach, economic factors such as potential land values and tenure arrangements are often ignored. Tradable landuse rights are proposed as an alternative economic mechanism for selecting reserves. Under this approach economic considerations determine the spatial distribution of development and reserves are allocated to sites with the lowest development value, minimizing the cost of the reserve network. The configuration of the reserve network as well as the biodiversity outcome is determined as a residual. However cost savings can be used to increase the total amount of area in reserve and improve biodiversity outcomes. The appropriateness of this approach for regional planning is discussed in light of key uncertainties associated with biodiversity protection. A comparison of biodiversity outcomes and costs under ecological versus economic approaches is undertaken for the Boreal Forest Natural Region of Alberta, Canada. We find a significant increase in total area protected and an increase in species representation under the TLR approach

Investments in Gas Pipelines and Liquefied Natural Gas Infrastructure. What is the Impact on the Security of Supply?

This paper addresses the question of the infrastructure investment required for gas pipeline and liquefied natural gas (LNG) connections to meet growing gas demand in an enlarged EU over the next 20 years. Several issues are presented, bearing in mind the major objective of the security of supply for EU countries. First, to set the scene, recent projections of gas demand in an enlarged EU are presented along with the corresponding need for additional imports. Then a scenario is developed showing possible supply routes to meet the import gap, relying on increasingly remote routes. An impressive bill of $150 to 200 billion will have to be paid for extending and building the required infrastructure in pipeline links and LNG-receiving facilities. The expected major development of LNG markets is subject to a particular discussion, as far as the progressive globalisation of this market and its inherent flexibility provide major advantages in terms of the security of supply, despite more costly infrastructure than pipeline links. The impact of technological progress is expected to reduce both capital investment and unit transport costs, offering access to new supply opportunities. Finally, the question of major obstacles to the realisation of the required huge investments in gas infrastructure over the next 20 years is addressed, opening hot debate on the subjects of future gas price, market liberalisation and financing issues