Using register data to assess the impact of response enhancement methods on the risk of nonresponse bias and survey costs

The pursuit of high response rates to minimise the threat of nonresponse bias continues to dominate decisions about resource allocation in survey research. Yet a growing body of research has begun to question this practice. In this study, we use previously unavailable data from a new sampling frame based on population registers to assess the value of different methods designed to increase response rates on the European Social Survey in Switzerland. Using sampling data provides information about both respondents and nonrespondents, making it possible to examine how changes in response rates resulting from the use of different fieldwork methods relate to changes in the composition and representativeness of the responding sample. We compute an R-indicator to assess representativity with respect to the sampling register variables, and find little improvement in the sample composition as response rates increase. We then examine the impact of response rate increases on the risk of nonresponse bias based on Maximal Absolute Bias (MAB), and coefficients of variation between subgroup response rates, alongside the associated costs of different types of fieldwork effort. The results show that increases in response rate help to reduce MAB, while only small but important improvements to sample representativity are gained by varying the type of effort. These findings lend further support to research that has called into question the value of extensive investment in procedures aimed at reaching response rate targets and the need for more tailored fieldwork strategies aimed both at reducing survey costs and minimising the risk of bias.

Common variation in PHACTR1 is associated with susceptibility to cervical artery dissection.

Cervical artery dissection (CeAD), a mural hematoma in a carotid or vertebral artery, is a major cause of ischemic stroke in young adults although relatively uncommon in the general population (incidence of 2.6/100,000 per year). Minor cervical traumas, infection, migraine and hypertension are putative risk factors, and inverse associations with obesity and hypercholesterolemia are described. No confirmed genetic susceptibility factors have been identified using candidate gene approaches. We performed genome-wide association studies (GWAS) in 1,393 CeAD cases and 14,416 controls. The rs9349379[G] allele (PHACTR1) was associated with lower CeAD risk (odds ratio (OR) = 0.75, 95% confidence interval (CI) = 0.69-0.82; P = 4.46 × 10(-10)), with confirmation in independent follow-up samples (659 CeAD cases and 2,648 controls; P = 3.91 × 10(-3); combined P = 1.00 × 10(-11)). The rs9349379[G] allele was previously shown to be associated with lower risk of migraine and increased risk of myocardial infarction. Deciphering the mechanisms underlying this pleiotropy might provide important information on the biological underpinnings of these disabling conditions.

Comparison of human and rhesus macaque T-cell responses elicited by boosting with NYVAC encoding human immunodeficiency virus type 1 clade C immunogens.

Rhesus macaques (Macaca mulatta) have played a valuable role in the development of human immunodeficiency virus (HIV) vaccine candidates prior to human clinical trials. However, changes and/or improvements in immunogen quality in the good manufacturing practice (GMP) process or changes in adjuvants, schedule, route, dose, or readouts have compromised the direct comparison of T-cell responses between species. Here we report a comparative study in which T-cell responses from humans and macaques to HIV type 1 antigens (Gag, Pol, Nef, and Env) were induced by the same vaccine batches prepared under GMP and administered according to the same schedules in the absence and presence of priming. Priming with DNA (humans and macaques) or alphavirus (macaques) and boosting with NYVAC induced robust and broad antigen-specific responses, with highly similar Env-specific gamma interferon (IFN-gamma) enzyme-linked immunospot assay responses in rhesus monkeys and human volunteers. Persistent cytokine responses of antigen-specific CD4(+) and CD8(+) T cells of the central memory as well as the effector memory phenotype, capable of simultaneously eliciting multiple cytokines (IFN-gamma, interleukin 2, and tumor necrosis factor alpha), were induced. Responses were highly similar in humans and primates, confirming earlier data indicating that priming is essential for inducing robust NYVAC-boosted IFN-gamma T-cell responses. While significant similarities were observed in Env-specific responses in both species, differences were also observed with respect to responses to other HIV antigens. Future studies with other vaccines using identical lots, immunization schedules, and readouts will establish a broader data set of species similarities and differences with which increased confidence in predicting human responses may be achieved.

Acute mesenteric vein thrombosis: factors associated with evolution to chronic mesenteric vein thrombosis

OBJECTIVE. Acute mesenteric venous thrombosis signs at MDCT are well described, but the literature lacks studies assessing their evolution. We aimed to describe the radiologic evolution of isolated acute mesenteric venous thrombosis and associated prognostic factors. MATERIALS AND METHODS. Patients with isolated acute mesenteric venous thrombosis with follow-up for a minimum of 1 month with MDCT were selected. Images at the acute phase and on follow-up were reviewed in consensus reading. For acute mesenteric venous thrombosis, we searched for low-attenuated intraluminal filling defect. For chronic mesenteric venous thrombosis, we searched for vessel stenosis or occlusion associated with collateral mesenteric veins. Treatment, thrombosis risk factor, symptoms, location, and length and diameter of mesenteric venous thrombosis were reported and correlated with evolution over time. RESULTS. Twenty patients (nine women and 11 men; mean age, 52 years) were selected. Four patients recovered without radiologic sequelae, and 16 developed chronic mesenteric venous thrombosis signs. Anticoagulation did not influence recovery (p = 1). Patients with recovery compared with patients with chronic mesenteric venous thrombosis showed more frequent central lesions (p = 0.03). At diagnosis, the thrombosed segment was shorter and larger in the complete radiologic recovery group compared with the chronic mesenteric venous thrombosis signs group: mean length (± SD) 6.25 ± 3.21 cm and 12.81 ± 5.96 cm, respectively (p = 0.01); mean transverse diameter 1.82 ± 0.42 cm and 1.12 ± 0.34 cm, respectively (p = 0.01). Mesenteric fat infiltration at diagnosis was more frequent in the chronic mesenteric venous thrombosis signs group than in the complete recovery group (p = 0.03). CONCLUSION. Most cases of acute mesenteric venous thrombosis evolve toward the chronic form with vein stenosis or occlusion and development of collateral veins. Location, length of mesenteric venous thrombosis, transverse diameter of the vein, and mesenteric fat infiltration at diagnosis are determinant factors for mesenteric venous thrombosis evolution.

Aerosol immunization with NYVAC and MVA vectored vaccines is safe, simple, and immunogenic.

Each year, approximately five million people die worldwide from putatively vaccine-preventable mucosally transmitted diseases. With respect to mass vaccination campaigns, one strategy to cope with this formidable challenge is aerosol vaccine delivery, which offers potential safety, logistical, and cost-saving advantages over traditional vaccination routes. Additionally, aerosol vaccination may elicit pivotal mucosal immune responses that could contain or eliminate mucosally transmitted pathogens in a preventative or therapeutic vaccine context. In this current preclinical non-human primate investigation, we demonstrate the feasibility of aerosol vaccination with the recombinant poxvirus-based vaccine vectors NYVAC and MVA. Real-time in vivo scintigraphy experiments with radiolabeled, aerosol-administered NYVAC-C (Clade C, HIV-1 vaccine) and MVA-HPV vaccines revealed consistent mucosal delivery to the respiratory tract. Furthermore, aerosol delivery of the vaccines was safe, inducing no vaccine-associated pathology, in particular in the brain and lungs, and was immunogenic. Administration of a DNA-C/NYVAC-C prime/boost regime resulted in both systemic and anal-genital HIV-specific immune responses that were still detectable 5 months after immunization. Thus, aerosol vaccination with NYVAC and MVA vectored vaccines constitutes a tool for large-scale vaccine efforts against mucosally transmitted pathogens.

Canakinumab (Acz885) Relieves Pain And Controls Inflammation Rapidly In Patients With Difficult-To-Treat Gouty Arthritis : Comparison With Triamcinolone Acetonide

Background : Monosodium urate (MSU) crystals stimulate the productionof interleukin-1b (IL-1b), a potent inflammatory cytokine. Targeted IL-1b blockade with canakinumab, a fully human monoclonal anti-IL-1b antibody, is a novel treatment for gouty arthritis. Its effects on pain and inflammation in acute gouty arthritis flares were compared with triamcinolone acetonide (TA). TA has been shown to be effective in the treatment of acute gouty arthritis flares.Methods : This was an 8-week, dose-ranging, multicenter, blinded, active-controlled trial. Patients _18 to _80 years with an acute gouty arthritis flare, refractory to or contraindicated to NSAIDs and/or colchicine were randomized to one subcutaneous dose of canakinumab (10, 25, 50, 90, or 150 mg; n¼143) or one intramuscular dose of TA (40 mg; n¼57). Primary outcome was pain intensity at 72 hours post dose on VAS scale (0-100 mm). Secondary outcomes included Creactive protein (CRP), serum amyloid A (SAA), and physician's assessment of tenderness, swelling and erythema of target joint at 72 hours, 7 days, 4 and 8-weeks post dose.Results : 191/200 patients completed the study. Canakinumab showed a statistically significant dose response at 72 hours. The 150mg dose group reached superior pain relief compared to TA group starting from 24 hours as previously reported. At 72 hours post dose, 78% of canakinumab 150mg treated patients achieved _75% and 96% achieved _50% reduction in pain from baseline. In contrast, 45% and 61% of patients treated with TA achieved _75% and _50% pain reduction, respectively. Median CRP/SAA levels were normalized by Day 7 for all canakinumab doses above 10mg and remained below the upper limit of normal [(ULN): CRP 3.0 mg/L; SAA 6.7 mg/L)] for rest of the study. In TA group, median CRP levels remained above the ULN throughout the study while median SAA levels decreased below ULN only 28 days after first dose. At 72 hours post dose, canakinumab 150mg group was 3.2 (95% CI, 1.27-7.89) times more likely to have less joint tenderness and 2.7 (95% CI, 1.09-6.5) times more likely to have less joint swelling than TA group (p<0.05). At 72 hours post dose, erythema disappeared in 74.1% of patients receiving canakinumab150mg and 69.6% of patients receiving TA. At 7 days post dose, erythema was absent in 96.3% of canakinumab 150mg treated patients vs. 83.9% of patients receiving TA. The overall incidence of AEs was similar for canakinumab (41%) and triamcinolone acetonide (42%). Serious AEs (canakinumab treatment groups n¼4, TA n¼1) were not considered treatment-related by investigators. No discontinuationsdue to AEs occurred.Conclusions : Canakinumab 150mg provided superior pain relief compared to TA for acute flares in difficult-to-treat gouty arthritis patients. Canakinumab provided rapid normalization of markers of inflammation accompanied by reduction of clinical signs and symptoms of inflammation.Disclosure statement : U.A., V.M., D.R. and P.S. are shareholders and employees of Novartis Pharma AG. A.P. has received research support from Novartis Pharma AG. N.S. has received research support from and acts as a consultant for Novartis Pharmaceuticals Corporation, has served on advisory boards for Novartis, Takeda, Savient, URL Pharma and Enzyme Rx, and is/has been a member of a speakers' bureau for Takeda. A.S. has received consultancy fees from Novartis Pharma AG, Abbott, Wyeth, UCB, Roche, MSD, Pfizer, Essex and Bristol-Myers Squibb. All other authors have declared no conflicts of interest.

Alterations of the 5'untranslated region of SLC16A12 lead to age-related cataract.

PURPOSE. Knowledge of genetic factors predisposing to age-related cataract is very limited. The aim of this study was to identify DNA sequences that either lead to or predispose for this disease. METHODS. The candidate gene SLC16A12, which encodes a solute carrier of the monocarboxylate transporter family, was sequenced in 484 patients with cataract (134 with juvenile cataract, 350 with age-related cataract) and 190 control subjects. Expression studies included luciferase reporter assay and RT-PCR experiments. RESULTS. One patient with age-related cataract showed a novel heterozygous mutation (c.-17A>G) in the 5'untranslated region (5'UTR). This mutation is in cis with the minor G-allele of the single nucleotide polymorphism (SNP) rs3740030 (c.-42T/G), also within the 5'UTR. Using a luciferase reporter assay system, a construct with the patient's haplotype caused a significant upregulation of luciferase activity. In comparison, the SNP G-allele alone promoted less activity, but that amount was still significantly higher than the amount of the common T-allele. Analysis of SLC16A12 transcripts in surrogate tissue demonstrated striking allele-specific differences causing 5'UTR heterogeneity with respect to sequence and quantity. These differences in gene expression were mirrored in an allele-specific predisposition to age-related cataract, as determined in a Swiss population (odds ratio approximately 2.2; confidence intervals, 1.23-4.3). CONCLUSIONS. The monocarboxylate transporter SLC16A12 may contribute to age-related cataract. Sequences within the 5'UTR modulate translational efficiency with pathogenic consequences.

Patterns of pain-free response in 497 cases of classic trigeminal neuralgia treated with Gamma Knife surgery and followed up for least 1 year.

Object The goal of this study was to establish whether clear patterns of initial pain freedom could be identified when treating patients with classic trigeminal neuralgia (TN) by using Gamma Knife surgery (GKS). The authors compared hypesthesia and pain recurrence rates to see if statistically significant differences could be found. Methods Between July 1992 and November 2010, 737 patients presenting with TN underwent GKS and prospective evaluation at Timone University Hospital in Marseille, France. In this study the authors analyzed the cases of 497 of these patients, who participated in follow-up longer than 1 year, did not have megadolichobasilar artery- or multiple sclerosis-related TN, and underwent GKS only once; in other words, the focus was on cases of classic TN with a single radiosurgical treatment. Radiosurgery was performed with a Leksell Gamma Knife (model B, C, or Perfexion) using both MR and CT imaging targeting. A single 4-mm isocenter was positioned in the cisternal portion of the trigeminal nerve at a median distance of 7.8 mm (range 4.5-14 mm) anterior to the emergence of the nerve. A median maximum dose of 85 Gy (range 70-90 Gy) was delivered. Using empirical methods and assisted by a chart with clear cut-off periods of pain free distribution, the authors were able to divide patients who experienced freedom from pain into 3 separate groups: patients who became pain free within the first 48 hours post-GKS; those who became pain free between 48 hours and 30 days post-GKS; and those who became pain free more than 30 days after GKS. Results The median age in the 497 patients was 68.3 years (range 28.1-93.2 years). The median follow-up period was 43.75 months (range 12-174.41 months). Four hundred fifty-four patients (91.34%) were initially pain free within a median time of 10 days (range 1-459 days) after GKS. One hundred sixty-nine patients (37.2%) became pain free within the first 48 hours (Group PF(≤ 48 hours)), 194 patients (42.8%) between posttreatment Day 3 and Day 30 (Group PF((>48 hours, ≤ 30 days))), and 91 patients (20%) after 30 days post-GKS (Group PF(>30 days)). Differences in postoperative hypesthesia were found: in Group PF(≤ 48 hours) 18 patients (13.7%) developed postoperative hypesthesia, compared with 30 patients (19%) in Group PF((>48 hours, ≤ 30 days)) and 22 patients (30.6%) in Group PF(>30 days) (p = 0.014). One hundred fifty-seven patients (34.4%) who initially became free from pain experienced a recurrence of pain with a median delay of 24 months (range 0.62-150.06 months). There were no statistically significant differences between the patient groups with respect to pain recurrence: 66 patients (39%) in Group PF(≤ 48 hours) experienced pain recurrence, compared with 71 patients (36.6%) in Group PF((>48 hours, ≤ 30 days)) and 27 patients (29.7%) in Group PF(>30 days) (p = 0.515). Conclusions A substantial number of patients (169 cases, 37.2%) became pain free within the first 48 hours. The rate of hypesthesia was higher in patients who became pain free more than 30 days after GKS, with a statistically significant difference between patient groups (p = 0.014).

Impact of etanercept-methotrexate therapy on patient-reported outcomes in rheumatoid arthritis patients with up to 12 months of symptoms.

Background/Purpose: Patient-reported outcomes (PROs) in patients with rheumatoid arthritis (RA) are critical in evaluating RA treatment effects on function and health-related quality of life (HR-QoL). Significant improvement in PROs has been reported in RA studies of biologic agents, including etanercept (ETN), but most studies have been conducted in patients with established disease. In addition to assessing treatment effects in early RA, there is interest in therapeutic strategies that allow dose reduction or withdrawal of biologic therapy (biologic-free) after induction of response. The PRIZE trial is an ongoing, 3-period study to evaluate the efficacy of combined ETN and methotrexate (MTX) therapy in patients with early, moderate-to-severe RA and to assess whether efficacy (remission) can be maintained with ETN dose reduction or biologic-free (Period 2) or drug-free (Period 3). Herein we report PROs associated with ETN 50 mg QW plus MTX (ETN50/MTX) therapy administered for 52 wks in Period 1 (induction) of the PRIZE trial. Methods: In Period 1, MTX- and biologic-naı‥ve patients with early, active RA (symptom onset 12 mo from enrollment; DAS28 _3.2) received open-label ETN50/MTX for 52 wks. The starting dose of MTX was 10 mg QW; at the discretion of the investigator, titration was permitted up to a maximum of 25 mg QW to achieve remission. Corticosteroid boosts were administered to patients not achieving low disease state at wks 13 and 26, unless contraindicated or not tolerated. PROs were assessed using the Health Assessment Questionnaire (HAQ) total score; Patient Acceptable Symptom State (PASS); EuroQol-5 Dimensions (EQ-5D) total index; Short Form Health Survey (SF-36); Functional Assessment of Chronic Illness Therapy (FACIT)-Fatigue; Work Instability Scale for Rheumatoid Arthritis (RAWIS); and Work Productivity and Activity Impairment Questionnaire: Rheumatoid Arthritis (WPAI:RA). Results: A total of 306 patients received treatment in Period 1 (mITT population); 222 (73%) patients completed the period. The majority of patients were female (70%), with a mean age of 50 y, mean DAS28 of 6.0 (median, 6.0), and duration of disease symptoms from onset of 6.5 months (median, 6.3 mo). Significant and clinically meaningful improvements in PROs, including in HAQ, EQ-5D, SF-36, and FACIT-Fatigue, were demonstrated with ETN50/MTX therapy from baseline to the final on therapy visit (Table; P_0.0001). Similar improvements were observed in all dimensions of RA-WIS and WPAI:RA (Table; P_0.0001). Conclusion: Combination therapy with ETN50/MTX for 52 wks in patients with _12 mo of symptomatic, active RA resulted in significant, clinically important improvements in measures of physical function, including normal HAQ (66.6% of patients), HR-QoL, fatigue, and work productivity. These outcomes are consistent with those reported in prior studies in patients with more established disease.

Long-term and long range migration of radioisotopes in terrestrial systems : mechanisms of radioisotopes (Cs, Sr, Pu, Am) mobilization in soils

Summary Artificial radionuclides were released in the environment during the atmospheric nuclear weapon tests and after accidental events involving nuclear industries. As a primary receptor of the deposition, the soil is a very sensitive compartment and understanding the interaction and migration of radionuclides within soils allows the development of scenario for the contamination risk of the population and of the environment. Most available field studies on radionuclides in soils only concern one or two isotopes, mostly 137Cs, and few physico-chemical soil parameters. The purpose of this study was a broader understanding of the radioecology of an Alpine valley. In a first part, we aimed to describe the depth distribution of 137Cs, 90Sr, 239+240Pu, and 241Am within different alpine soils and to identify some stable elements as indicators for accumulating layers. In the central part of the study, the goal was to investigate the repartition of ^Sr and 239Pu between the truly dissolved fraction and the colloidal fraction of the soil solutions and to identify the nature of colloids involved in the adsorption of ^Sr and 239Pu. These results were integrated in an "advection- sorption" transport model seeking to explain the migration of 239Pu and 90Sr within the soils and to assess the importance of colloidal transport for these two isotopes. A further aspect studied was the role of the competition between the radioisotopes (137Cs and 90Sr) and their stable chemical analogues (K and Ca) with respect to plant uptake by different plant species. The results on the depth distribution within the soils showed that 137Cs was mostly retained in the topsoil, to the exception of an organic-rich soil (Histosol 2) receiving important surface runoff, where migration down to a depth of 30 cm was observed. 137Cs depth distribution within the soils was similar to unsupported 210Pb depth distribution. The plant uptake of 137Cs clearly depended on the concentration of exchangeable potassium in the soils. Moreover, we showed that the 137Cs uptake by certain species of the taxonomic orders Poales and Rosales was more sensitive to the increase in exchangeable Κ compared to other orders. Strontium-90 was much more mobile in the soils than 137Cs and depth migration and accumulation in specific AI- and Fe-rich layers were found down to 30 cm. Copper and Ni showed accumulations in these same layers, indicating their potential to be used as indicators for the migration of ^Sr within the soils. In addition, we observed a 90Sr activity peak in the topsoil that can be attributable to recycling of 90Sr by plant uptake. We demonstrated for the first time that a part of 90Sr (at least 40%) was associated with the colloids in organic-rich soil solutions. Therefore, we predict a significant effect of the colloidal migration of ^Sr in organic-rich soil solutions. The plant uptake results for 90Sr indicated a phylogenetic effect between Non-Eudicot and Eudicots: the order Poales concentrating much less 90Sr than Eudicots do. Moreover, we were able to demonstrate that the sensitivity of the 90Sr uptake by 5 different Alpine plant species to the amount of exchangeable Ca was species-independent. Plutonium and 241Am accumulated in the second layer of all soils and only a slight migration deeper than 20 cm was observed. Plutonium and 241Am showed a similar depth distribution in the soils. The model results suggested that the present day migration of 239Pu was very slow and that the uptake by plants was negligible. 239Pu activities between 0.01 to 0.08 mBq/L were measured in the bulk soil solutions. Migration of 239Pu with the soil solution is dominated by colloidal transport. We reported strong evidences that humic substances were responsible of the sorption of 239Pu to the colloidal fraction of the soil solutions. This was reflected by the strong correlation between 239Pu concentrations and the content of (colloidal) organic matter in the soil solution. Résumé Certains radioéléments artificiels ont été disséminés dans l'environnement suite aux essais atmosphériques de bombes nucléaires et suite à des accidents impliquant les industries nucléaires. En tant que récepteur primaire de la déposition, le sol est un compartiment sensible et des connaissances sur les interactions et la migration des radioéléments dans le sol permettent de développer des modèles pour estimer la contamination de la population et de l'environnement. Actuellement, la plupart des études de terrain sur ce sujet concernent uniquement un ou deux radioéléments, surtout le 137Cs et peu d'études intègrent les paramètres du sol pour expliquer la migration des radioéléments. Le but général de cette étude était une compréhension étendue de la radio-écologie d'une vallée alpine. Notre premier objectif était de décrire la distribution en profondeur de 137Cs, ^Sr, 239+240pu et 241Am dans différents sols alpins en relation avec des éléments stables du sol, dans le but d'identifier des éléments stables qui pourraient servir d'indicateurs pour des horizons accumulateurs. L'objectif de la deuxième partie, qui était la partie centrale de l'étude, était d'estimer le pourcentage d'activité sous forme colloïdale du 239Pu et du 90Sr dans les solutions des sols. De plus nous avons déterminé la nature des colloïdes impliqués dans la fixation du ^Sr et 239Pu. Nous avons ensuite intégré ces résultats dans un modèle de transport développé dans le but de décrire la migration du 239Pu et 90Sr dans le sol. Finalement, nous avons étudié l'absorption de 137Cs et 90Sr par les plantes en fonction de l'espèce et de la compétition avec leur élément analogue stable (K et Ca). Les résultats sur la migration en profondeur du 137Cs ont montré que ce radioélément était généralement retenu en surface, à l'exception d'un sol riche en matière organique dans lequel nous avons observé une nette migration en profondeur. Dans tous les sols, la distribution en profondeur du 137Cs était corrélée avec la distribution du 210Pb. L'absorption du 137Cs par les plantes, était dépendante de la concentration en Κ échangeable dans le sol, le potassium étant un compétiteur. De plus, nous avons observé que les espèces ne réagissaient pas de la même manière aux variations de la concentration de Κ échangeable. En effet, les espèces appartenant aux ordres des Poales et des Rosales étaient plus sensibles aux variations de potassium échangeable dans le sol. Dans tous les sols Le 90Sr était beaucoup plus mobile que le 137Cs. En effet, nous avons observé des accumulations de 90Sr dans des horizons riches en Fe et Al jusqu'à 30 cm de profondeur. De plus, le Cu et le Ni montraient des accumulations dans les mêmes horizons que le 90Sr, indiquant qu'il pourrait être possible d'utiliser ces deux éléments comme analogues pour la migration du 90Sr. D'après le modèle développé, le pic de 90Sr dans les premiers centimètres du sol peut être attribué à du recyclage par les plantes. Le 90Sr en solution était principalement sous forme dissoute dans des solutions de sols peu organique (entre 60 et 100% de 90Sr dissous). Par contre, dans des solutions organiques, un important pourcentage de 90Sr (plus de 40%) était associé aux colloïdes. La migration colloïdale du 90Sr peut donc être significative dans des solutions organiques. Comme pour le 137Cs, l'absorption du 90Sr par les plantes dépendait de la concentration de son analogue chimique dans la fraction échangeable du sol. Par contre, les espèces de plantes étudiées avaient la même sensibilité aux variations de la concentration du calcium échangeable. Le plutonium et l'américium étaient accumulés dans le deuxième horizon du sol et nous avons observé seulement une faible migration plus profondément que 20 cm. Selon le modèle, la migration actuelle du plutonium est très lente et l'absorption par les plantes semble négligeable. Nous avons mesuré entre 0.01 et 0.08 mBq/L de 239Pu dans les solutions de sol brutes. La migration du plutonium par la solution du sol est due principalement aux colloïdes, probablement de nature humique. Résumé grand public Dans les années 1950 à 1960, l'environnement a été contaminé par des éléments radioactifs (radioéléments) artificiels provenant des essais des armes atomiques et de l'industrie nucléaire. En effet, durant ces années, les premiers essais de bombes atomiques se faisaient dans l'atmosphère, libérant de grandes quantités d'éléments radioactifs. De plus certains accidents impliquant l'industrie nucléaire civile ont contribué à la dissémination d'éléments radioactifs dans l'environnement. Ce fut par exemple le cas de l'accident de la centrale atomique de Tchernobyl en 1986 qui a causé une importante contamination d'une grande partie de l'Europe par le 137Cs. Lorsqu'ils sont libérés dans l'atmosphère, les radioéléments sont dispersés et transportés par les courants atmosphériques, puis peuvent être déposés dans l'environnement, principalement par les précipitations. Une fois déposés sur le sol, les radioéléments vont interagir avec les composants du sol et migrer plus ou moins vite. La connaissance des interactions des éléments radioactifs avec le sol est donc importante pour prédire les risques de contamination de l'environnement et de l'homme. Le but général de ce travail était d'évaluer la migration de différents éléments radioactifs (césium-137, strontium-90, plutonium et américium-241) à travers le sol. Nous avons choisi un site d'étude en milieu alpin (Val Piora, Tessin, Suisse), contaminé en radioéléments principalement par les retombées de l'accident de Tchernobyl et des essais atmosphériques de bombes atomiques. Dans un premier temps, nous avons caractérisé la distribution en profondeur des éléments radioactifs dans le sol et l'avons comparée à divers éléments stables. Cette comparaison nous a permit de remarquer que le cuivre et le nickel s'accumulaient dans les mêmes horizons du sol que le strontium-90 et pourraient donc être utilisés comme analogue pour la migration du strontium-90 dans les sols. Dans la plupart des sols étudiés, la migration du césium-137, du plutonium et de l'américium-241 était lente et ces radioéléments étaient donc accumulés dans les premiers centimètres du sol. Par contre, le strontium-90 a migré beaucoup plus rapidement que les autres radioéléments si bien qu'on observe des accumulations de strontium-90 à plus de 30 cm de profondeur. Les radioéléments migrent dans la solution du sol soit sous forme dissoute, soit sous forme colloïdale, c'est-à-dire associés à des particules de diamètre < Ιμηι. Cette association avec des colloïdes permet à des radioéléments peu solubles, comme le plutonium, de migrer plus rapidement qu'attendu. Nous avons voulu savoir quelle était la part de strontium-90 et plutonium associés à des colloïdes dans la solution du sol. Les résultats ont montré que le plutonium en solution était principalement associé à des colloïdes de type organique. Quant au strontium-90, ce dernier était en partie associé à des colloïdes dans des solutions de sol riches en matière organique, par contre, il était principalement sous forme dissoute dans les solutions de sol peu organiques. L'absorption de radioéléments par les plantes représente une voie importante pour le transfert vers la chaîne alimentaire, par conséquent pour la contamination de l'homme. Nous avons donc étudié le transfert du césium-137 et du strontium-90 de plusieurs sols vers différentes espèces de plantes. Les résultats ont montré que l'absorption des radioéléments par les plantes était liée à la concentration de leur analogue chimique (calcium pour le strontium-90 et potassium pour le césium- 137) dans la fraction échangeable du sol. De plus certaines espèces de plantes accumulent significativement moins de strontium-90.

Iterative statistical reconstruction method: A new way to reduce dose in pediatric cardiac CT

Purpose: Although several approaches have been already used to reduce radiation dose, CT doses are still among the high doses in radio-diagnostic. Recently, General Electric introduced a new imaging reconstruction technique, adaptive statistical iterative reconstruction (ASIR), allows to taking into account the statistical fluctuation of noise. The benefits of ASIR method were assessed through classic metrics and the evaluations of cardiac structures by radiologists. Methods and materials: A 64-row CT (MDCT) was employed. Catphan600 phantom acquisitions and 10 routine-dose CT examinations performed at 80 kVp were reconstructed with FBP and with 50% of ASIR. Six radiologists then assessed the visibility of main cardiac structures using the visual grading analysis (VGA) method. Results: On phantoms, for a constant value of SD (25 HU), CTDIvol is divided by 2 (8 mGy to 4 mGy) when 50% of ASIR is used. At constant CTDIvol, MTF medium frequencies were also significantly improved. First results indicated that clinical images reconstructed with ASIR had a better overall image quality compared with conventional reconstruction. This means that at constant image quality the radiation dose can be strongly reduced. Conclusion: The first results of this study shown that the ASIR method improves the image quality on phantoms by decreasing noise and improving resolution with respect to the classical one. Moreover, the benefit obtained is higher at lower doses. In clinical environment, a dose reduction can still be expected on 80 kVp low dose pediatric protocols using 50% of iterative reconstruction. Best ASIR percentage as a function of cardiac structures and detailed protocols will be presented for cardiac examinations.

Comparison of a multiplexed bead-based assay with an immunofluorescence and an enzyme-immuno assay for the assessment of Epstein-Barr virus serologic status.

We have compared a multiplexed bead-based assay (BBA) with an enzyme immunoassay (EIA) and immunofluorescence assay (IFA) for the assessment of the Epstein-Barr virus (EBV) serostatus. Three hundred and ninety-three sera, classified according to IFA results as seronegative (n=100), acute infection (n=100), past infection (n=100) and indeterminate (n=93), were tested by BBA and EIA. Overall, the three methods gave similar results with a relatively high (75.2%) concordance with the consensus interpretation of the serostatus. The most significant discordances were: (i) 58 samples had uninterpretable results for BBA, in majority due to the detection of non-antigen specific antibody binding by control beads. (ii) almost half the samples positive for anti-Epstein-Barr nuclear antigen (EBNA) IgG by BBA or EIA were negative by IFA. Among the latter, only a minority had a history of immunocompromise or treatment, or detectable anti-early antigen antibody. This discrepancy probably reflects a poor sensitivity of IFA for anti-EBNA IgG detection. EIA and BBA had a similar performance and had substantial practical advantages over IFA with respect to testing for EBV serostatus.

Inter- and intraobserver variability of measurements with Pentacam HR® in patients with mild to moderate keratoconus

Purpose: To evaluate inter- and intraobserver variability of indices crucial for detection of keratoconus progression derived from the Pentacam HR® (high-resolution) tomographer (OCULUS Optikgeräte GmbH, Wetzlar, Germany) in patients with mild to moderate keratoconus. Methods: Three repeated corneal topography measurements in the 25-picture mode by two independent observers were performed. The extent of variability across a large range of measurement parameters was analyzed including anterior and posterior corneal surface measurements, pachymetry values, corneal volume, anterior chamber volume and depth, and iridocorneal angle. The intraclass correlation coefficient (ICC) between and within each investigator was calculated to assess reproducibility and repeatability, respectively. Results: 31 eyes of 20 patients (mean age 31.6, SD ± 8.6) were included. Overall, the repeatability and reproducibility were excellent. The range of variability was reported by calculating the standard deviation of measurements. The detailed results are shown in Table 1. Conclusions: This study shows that the Pentacam HR® tomographer provides reliable measurements in patients with mild to moderate keratoconus. However, all parameters showed a certain range of variability. This should be taken into account when assessing keratoconus progression in order to distinguish true progression from variability in measurements. In addition, the excellent reproducibility suggests that the measurements can be reliably performed by different individuals from one visit to another.

Laparoscopic Pancreatic Enucleation With End-to-End Pancreatic Duct Reconstruction.

BACKGROUND: Laparoscopic enucleation for neuroendocrine pancreatic tumors has become a feasible technique, with a reported incidence of pancreatic fistula ranging from 13 to 29 %.1 (-) 3 This report describes the first successful case of laparoscopic pancreatic enucleation with resection of the main pancreatic duct followed by end-to-end anastomosis. METHODS: A 41-year-old woman was admitted to the authors' hospital for repeated syncope. Hypoglycemia also was noted. A contrast-enhanced computed tomography examination showed a highly enhanced tumor measuring 22 mm in diameter on the ventral side of the pancreatic body adjacent to the main pancreatic duct. The patient's blood insulin level was elevated, and her diagnosis was determined to be pancreatic insulinoma. Laparoscopic pancreatic enucleation was performed. Approximately 2 cm of the main pancreatic duct was segmentally resected, and a short stent (Silicone tube: Silastic, Dow Corning Corporation, Midland, MI) was inserted. The direct anastomosis of the main pancreatic duct was performed using four separate sutures with an absorbable monofilament (6-0 PDS). RESULTS: The operation time was 166 min, and the estimated blood loss was 100 mL. The postoperative course was uneventful, and the patient was discharged from hospital on postoperative day 7. The pathologic findings showed a well-differentiated insulinoma and a negative surgical margin. A computed tomography examination performed 1 month after the operation showed a successful anastomosis with a patent main pancreatic duct. CONCLUSIONS: Laparoscopic segmental resection of the main pancreatic duct and end-to-end anastomosis can be performed safely with the insertion of a short stent. This technique also can be used for a central pancreatectomy.

Decision curve analysis revisited: overall net benefit, relationships to ROC curve analysis, and application to case-control studies.

ABSTRACT: BACKGROUND: Decision curve analysis has been introduced as a method to evaluate prediction models in terms of their clinical consequences if used for a binary classification of subjects into a group who should and into a group who should not be treated. The key concept for this type of evaluation is the "net benefit", a concept borrowed from utility theory. METHODS: We recall the foundations of decision curve analysis and discuss some new aspects. First, we stress the formal distinction between the net benefit for the treated and for the untreated and define the concept of the "overall net benefit". Next, we revisit the important distinction between the concept of accuracy, as typically assessed using the Youden index and a receiver operating characteristic (ROC) analysis, and the concept of utility of a prediction model, as assessed using decision curve analysis. Finally, we provide an explicit implementation of decision curve analysis to be applied in the context of case-control studies. RESULTS: We show that the overall net benefit, which combines the net benefit for the treated and the untreated, is a natural alternative to the benefit achieved by a model, being invariant with respect to the coding of the outcome, and conveying a more comprehensive picture of the situation. Further, within the framework of decision curve analysis, we illustrate the important difference between the accuracy and the utility of a model, demonstrating how poor an accurate model may be in terms of its net benefit. Eventually, we expose that the application of decision curve analysis to case-control studies, where an accurate estimate of the true prevalence of a disease cannot be obtained from the data, is achieved with a few modifications to the original calculation procedure. CONCLUSIONS: We present several interrelated extensions to decision curve analysis that will both facilitate its interpretation and broaden its potential area of application.