Perspectives on tolerability and reasonableness.

Judgements on tolerability and reasonableness are central to the optimisation of protection. There are currently several international developments regarding these key considerations which will contribute to the review and evolution of the system of radiological protection. The IRPA15 International Congress brought together the principal issues currently under discussion, and the outcome of these discussions is presented.

Time-dependent resonant scattering: an analytical approach.

A time-dependent description is given of a scattering process involving a single resonance embedded in a set of flat continua. An analytical approach is presented which starts from an incident free particle wave packet and yields the Breit-Wigner cross-section formula at infinite times. We show that at intermediate times the so-called Wigner-Weisskopf approximation is equivalent to a scattering process involving a contact potential. Applications in cold-atom scattering and resonance enhanced desorption of molecules are discussed.

Surrogate markers predicting overall survival for lung cancer: ELCWP recommendations.

The present systematic review was performed under the auspices of the European Lung Cancer Working Party (ELCWP) in order to determine the role of early intermediate criteria (surrogate markers), instead of survival, in determining treatment efficacy in patients with lung cancer. Initially, the level of evidence for the use of overall survival to evaluate treatment efficacy was reviewed. Nine questions were then formulated by the ELCWP. After reviewing the literature with experts on these questions, it can be concluded that overall survival is still the best criterion for predicting treatment efficacy in lung cancer. Some intermediate criteria can be early predictors, if not surrogates, for survival, despite limitations in their potential application: these include time to progression, progression-free survival, objective response, local control after radiotherapy, downstaging in locally advanced nonsmall cell lung cancer (NSCLC), complete resection and pathological TNM in resected NSCLC, and a few circulating markers. Other criteria assessed in these recommendations are not currently adequate surrogates of survival in lung cancer.

Validation and comparison of several published prognostic systems for patients with small cell lung cancer.

The aim of the present study was to validate and compare published prognostic classifications for predicting the survival of patients with small cell lung cancer. We pooled data from phase III randomised clinical trials, and used Cox models for validation purposes and concordance probability estimates for assessing predictive ability. We included 693 patients. All the classifications impacted significantly on survival, with hazard ratios (HRs) in the range 1.57-1.68 (all p<0.0001). Median survival times were 16-19 months for the best predicted groups, while they were 6-7 months for the most poorly predicted groups. Most of the paired comparisons were statistically significant. We obtained similar results when restricting the analysis to patients with extensive disease. Multivariate Cox models for fitting survival data were also performed. The HRs for a single covariate were 8.23 (95% CI 5.88-11.69), and 9.46 (6.67-13.50), and for extensive disease were 5.60 (3.13-9.93), 12.49 (5.57-28.01) and 8.83 (4.66-16.64). Concordance probability estimates ranged 0.55-0.65 (overlapping confidence intervals). Published classifications were validated and suitable for use at a population level. As expected, prediction at an individual level remains problematic. A specific model designed for extensive-disease patients did not appear to perform better.

Management of abdominal emergencies in adults using telemedicine and artificial intelligence.

The terms "telemedicine" and "artificial intelligence" (AI) are used today throughout all fields of medicine, with varying degrees of relevance. If telemedicine corresponds to practices currently being developed to supply a high quality response to medical provider shortages in the general provision of healthcare and to specific regional challenges. Through the possibilities of "scalability" and the "augmented physician" that it has helped to create, AI may also constitute a revolution in our practices. In the management of surgical emergencies, abdominal pain is one of the most frequent complaints of patients who present for emergency consultation, and up to 20% of patients prove to have an organic lesion that will require surgical management. In view of the very large number of patients concerned, the variety of clinical presentations, the potential seriousness of the etiological pathology that sometimes involves a life-threatening prognosis, healthcare workers responsible for these patients have logically been led to regularly rely on imaging examinations, which remain the critical key to subsequent management. Therefore, it is not surprising that articles have been published in recent years concerning the potential contributions of telemedicine (and teleradiology) to the diagnostic management of these patients, and also concerning the contribution of AI (albeit still in its infancy) to aid in diagnosis and treatment, including surgery. This review article presents the existing data and proposes a collaborative vision of an optimized patient pathway, giving medical meaning to the use of these tools.

Synthesis and evaluation of amides surrogates of dopamine D3 receptor ligands.

Isosteric replacement of the amide function and modulation of the arylpiperazine moiety of known dopamine D3 receptor ligands led to potent and selective compounds. Enhanced bioavailability and preferential brain distribution make compound 6c a good candidate for pharmacological and clinical evaluation.

ICRP approach for radiological protection from NORM in industrial processes.

The International Commission on Radiological Protection (ICRP) recently issued ICRP Publication 142 on radiological protection from naturally occurring radioactive material (NORM) in industrial processes. Industries involving NORM may give rise to multiple hazards, and the radiological hazard is not necessarily dominant. They are diverse and may involve exposure of people and the environment where protective actions need to be considered. In some cases, there is a potential for significant routine exposure of workers and members of the public. Releases of large volumes of NORM may also result in detrimental effects on the environment from radiological and non-radiological constituents. However, industries involving NORM present no real prospect of a radiological emergency leading to tissue reactions or immediate danger for life. Radiological protection in these industries can be appropriately addressed on the basis of the principles of justification of the actions taken and optimisation of protection using reference levels. An integrated and graded approach is recommended for the protection of workers, the public, and the environment, where consideration of non-radiological hazards is integrated with the radiological hazards, and the approach to protection is optimised (graded) so that the use of various radiological protection programme elements is consistent with the hazards while not imposing unnecessary burdens.

Optimal level of inbreeding in the common lizard.

Mate choice with regard to genetic similarity has been rarely considered as a dynamic process. We examined this possibility in breeding populations of the common lizard (Lacerta vivipara) kept for several years in semi-natural conditions. We investigated whether they displayed a pattern of mate choice according to the genetic similarity and whether it was context-dependent. Mate choice depended on genetic similarity with the partner and also on age and condition. There was no systematic avoidance of inbreeding. Females of intermediate ages, more monogamous, did not mate with genetically similar partners, whereas younger and older females, more polyandrous, did but highest clutch proportions were associated with intermediate values of pair-relatedness. These results indicate dynamic mate choice, suggesting that individuals of different phenotypes select their partners in different ways according to their genetic similarity. We consider our results in the light of diverse and apparently contradictory theories concerning genetic compatibility, and particularly, optimal inbreeding and inclusive fitness.

A spectrophotometric transesterification-based assay for lipases in organic solvent.

A new method to evaluate lipase activities in nonaqueous conditions using vinyl ester absorbance at ultraviolet (UV) wavelengths is described. The model reaction is the transesterification between vinyl stearate and pentanol in hexane at 30 degrees C or in decane at 50 degrees C. The conversion of vinyl stearate into pentyl stearate is monitored through decreasing UV absorbance at 200 nm. Six commercial lipases were tested with this method, and results were compared with gas chromatography (GC) quantification and a classical spectrophotometric method using p-nitrophenyl palmitate. Results from the new spectrophotometric assay are similar both to results from GC quantification (R(2)=0.999) and to results from p-nitrophenyl palmitate (R(2)=0.989). The proposed method is able to evaluate both high activity from immobilized lipases such as immobilized Candida antarctica B lipase (3060 +/- 350 U g(-1)) and low activity from crude enzymatic extracts such as Carica papaya dried latex (0.1 +/- 0.04 U g(-1)). The method has also been used to measure kinetic parameters of C. antarctica B lipase for vinyl stearate and the correlation between its synthesis activity and its concentration. The method has also proved to be effective in studying the acyl selectivity of a lipase by comparing its activities with increasing chain lengths of vinyl esters.

Evaluation of the ability of antioxidants to counteract lipid oxidation: existing methods, new trends and challenges.

Oxidative degradation of lipids, especially that induced by reactive oxygen species (ROS), leads to quality deterioration of foods and cosmetics and could have harmful effects on health. Currently, a very promising way to overcome this is to use vegetable antioxidants for nutritional, therapeutic or food quality preservation purposes. A major challenge is to develop tools to assess the antioxidant capacity and real efficacy of these molecules. Many rapid in vitro tests are now available, but they are often performed in dissimilar conditions and different properties are thus frequently measured. The so-called 'direct' methods, which use oxidizable substrates, seem to be the only ones capable of measuring real antioxidant power. Some oxidizable substrates correspond to molecules or natural extracts exhibiting biological activity, such as lipids, proteins or nucleic acids, while others are model substrates that are not encountered in biological systems or foods. Only lipid oxidation and direct methods using lipid-like substrates will be discussed in this review. The main mechanisms of autoxidation and antioxidation are recapitulated, then the four components of a standard test (oxidizable substrate, medium, oxidation conditions and antioxidant) applied to a single antioxidant or complex mixtures are dealt with successively. The study is focused particularly on model lipids, but also on dietary and biological lipids isolated from their natural environment, including lipoproteins and phospholipidic membranes. Then the advantages and drawbacks of existing methods and new approaches are compared according to the context. Finally, recent trends based on the chemometric strategy are introduced as a highly promising prospect for harmonizing in vitro methods.

Exploring insect biodiversity: the parasitic Hymenoptera, chiefly Chalcidoidea, associated with seeds of asphodels (Xanthorrhoeaceae), with the description of nine new species belonging to Eurytomidae and Torymidae.

An account is given of the communities of Chalcidoidea, mostly based upon species of Bruchophagus Ashmead (Eurytomidae), which feed as larvae in seeds of Asphodelus and Asphodeline (Xanthorrhoeaceae). Eight new species of Eurytomidae, namely B. abscedus Askew sp. n., B. asphodelinae Askew Stojanova sp. n., B. gijswijti Askew Ribes sp. n., B. insulare Delvare sp. n., B. lecomtei Delvare sp. n., B. ribesi Askew sp. n., Eurytoma genale Askew Stojanova sp. n., and Aximopsis balajasi Delvare sp. n., are described together with the new species Idiomacromerus asphodeli Ribes sp. n. (Torymidae). Eurytoma setigera Mayr, 1878 is again synonymized with E. pistaciae Rondani, 1877 syn. rev. Puklina dillerae Doganlar, 1993 and P. asphodelinae Boyadzhiev, 2003 are synonymized with P. depilata Graham, 1987 syn n. The use, respectively of the mitochondrial genes COI and Cyt B and of the nuclear gene EF1-α, allowed us to discriminate pairs of sibling species in the three genera of Eurytomidae and to circumscribe the limits of the hypervariable Eurytoma asphodeli Hedqvist, 1976. The trophic webs associated with five species/subspecies of asphodels are fully described and illustrated, the distributions of the chalcid wasps involved are figured, and the phenology of the most common species is quoted and figured.

ICRP Publication 142: Radiological Protection from Naturally Occurring Radioactive Material (NORM) in Industrial Processes.

The purpose of this publication is to provide guidance on radiological protection in industries involving naturally occurring radioactive material (NORM). These industries may give rise to multiple hazards and the radiological hazard is not necessarily dominant. The industries are diverse and may involve exposure of people and the environment where protective actions need to be considered. In some cases, there is a potential for significant routine exposure of workers and members of the public if suitable control measures are not considered. Releases of large volumes of NORM may also result in detrimental effects on the environment from radiological and non-radiological constituents. However, NORM industries present no real prospect of a radiological emergency leading to tissue reactions or immediate danger for life. Radiological protection in industries involving NORM can be appropriately addressed on the basis of the principles of justification of the actions taken and optimisation of protection using reference levels. An integrated and graded approach is recommended for the protection of workers, the public, and the environment, where consideration of non-radiological hazards is integrated with radiological hazards, and the approach to protection is optimised (graded) so that the use of various radiological protection programme elements is consistent with the hazards while not imposing unnecessary burdens. For workers, the approach starts with characterisation of the exposure situation, and integration, as necessary, of specific radiological protective actions to complement the protection strategy already in place or planned to manage other workplace hazards. According to the characteristics of the exposure situation and the magnitude of the hazards, a relevant reference level should be selected and appropriate collective or individual protective actions taken. Exposure to radon is also treated using a graded approach, based first on application of typical radon prevention and mitigation techniques, as described in Publication 126. A similar approach should be implemented for public exposure through the control of discharges, wastes, and residues after characterisation of the situation. If the protection of non-human species is warranted, it should be dealt with after an assessment of radiological exposure appropriate for the circumstances, taking into account all hazards and impacts. This should include identification of exposed organisms in the environment, and use relevant derived consideration reference levels to inform decisions on options for control of exposure.

A phase III randomised study of concomitant induction radiochemotherapy testing two modalities of radiosensitisation by cisplatin (standard versus daily) for limited small-cell lung cancer.

BACKGROUND: The purpose of this study was to determine in limited small-cell lung cancer if locoregional irradiation concurrently with induction chemotherapy with cisplatin and etoposide prolongs survival when cisplatin is given daily as a radiosensitiser. PATIENTS AND METHODS: Two-hundred and four eligible patients were randomised between standard radiosensitised induction chemoradiotherapy (arm A) with cisplatin (90 mg/m(2) day 1) plus etoposide and daily radiosensitised induction chemoradiotherapy (arm B) with cisplatin (6 mg/m(2)/day) plus etoposide. Chemotherapy and chest irradiation (39.90 Gy in 15 fractions >3 weeks) both started on day 1. RESULTS: There was no difference in survival between both arms with respective median, 2 and 5 years of 15.5 months, 35% and 18% in arm A and 17.0 months, 38% and 21% in arm B (P = 0.50). Performance status and T status were identified as independent prognostic factors for survival. In terms of local control rate, there was a statistical trend in favour of arm A with 2% only local relapse versus 10% in arm B. Daily cisplatin radiosensitisation was associated with more oesophagitis and thrombopenia but less nephrotoxicity. CONCLUSION: Induction chemoradiotherapy resulted in both arms in good long-term survival, comparable to the best reported results and without improvement by daily cisplatin administration.

Critical parameters for the partial coalescence of a droplet.

The partial coalescence of a droplet onto a planar liquid-liquid interface is investigated experimentally by tuning the viscosities of both liquids. The problem mainly depends on four dimensionless parameters: The Bond number (gravity vs surface tension), the Ohnesorge numbers (viscosity in both fluids vs surface tension), and the density relative difference. The ratio between the daughter droplet size and the mother droplet size is investigated as a function of these dimensionless numbers. Global quantities such as the available surface energy of the droplet have been measured during the coalescence. The capillary waves propagation and damping are studied in detail. The relation between these waves and the partial coalescence is discussed. Additional viscous mechanisms are proposed in order to explain the asymmetric role played by both viscosities.

Foam control in fermentation bioprocess: from simple aeration tests to bioreactor.

In this article, we describe the development of a simple laboratory test for the effective screening of foam control agents on a selected fermentation system, the mass production of Yarrowia lipolytica. Aeration testing is based on sparging air in the foaming medium allowing partial reproduction of the gas-liquid hydrodynamic encountered in bioreactors. "Dynamic sparge test," for which measurements are made during foam formation, was used to compare the capacity of three antifoams, based on different technologies, to control the foam produced in the fermentation broth. The selected foam control agents were: (1) an organic antifoam (TEGO AFKS911), (2) a silicone-based emulsion containing in situ treated silica (DC-1520) and (3) a silicone/ organic blend silica-free formulation. The testing results demonstrated dramatic differences among them and showed that the capacity of TEGO AFKS911 and DC-1520 to control the foam generated in the fermentation broth decreases as a function of fermentation time. This occurred to a much lesser extent for the silicone/ organic blend formulation. These results were correlated with the change of the foam nature and the increase of foam stability of the fermentation broth with culture time. The increase in protein content as a function of growth time was correlated with an increase in foam stability and antifoam consumption. A "synthetic fermentation broth" was also developed, by adding both proteins and microorganism to the culture medium. This allowed us to mimic the fermentation broth, shown by the similar antifoams behaviour, and is therefore a simple methodology useful for the selection of appropriate antifoams.

Understanding existing exposure situations.

International Commission on Radiological Protection (ICRP) Publication 103 removed the distinction between practices and interventions, and introduced three types of exposure situation: existing, planned, and emergency. It also emphasised the optimisation principle in connection with individual dose restrictions for all controllable exposure situations. Existing exposure situations are those resulting from sources, natural or man-made, that already exist when a decision on control has to be taken. They have common features to be taken into account when implementing general recommendations, such as: the source may be difficult to control; all exposures cannot be anticipated; protective actions can only be implemented after characterisation of the exposure situation; time may be needed to reduce exposure below the reference level; levels of exposure are highly dependent on individual behaviour and present a wide spread of individual dose distribution; exposures at work may be adventitious and not considered as occupational exposure; there is generally no potential for accident; many stakeholders have to be involved; and many factors need to be considered. ICRP is currently developing a series of reports related to the practical implementation of Publication 103 to various existing exposure situations, including exposure from radon, exposure from cosmic radiation in aviation, exposure from processes using naturally occurring radioactive material, and exposure from contaminated sites due to past activities.

Characterization of heme orientational disorder in myoglobin by proton nuclear Overhauser effects.

Freshly reconstituted sperm whale myoglobin is a mixture of two components distinguishable by proton nuclear magnetic resonance. The two species are interconvertible and the equilibrium composition is about 90% of one form, the form studied by X-ray methods. We have used the nuclear Overhauser effect to characterize the other (minor) component in its metcyano complex. Whereas in the major form there is dipolar contact between residue 99 and the heme pyrrole ring III, in the minor form the same residue is in contact with pyrrole IV, related to ring III by a 180 degrees rotation about the alpha-gamma meso axis. This interaction proves the validity of the heme rotational disorder proposition and confirms that the apoprotein does not discriminate between the two sides of the heme in the rapid insertion process. It is proposed that the differences in nuclear Overhauser effect between the protein matrix and the heme moiety can be used to define qualitatively the structural consequences of this heterogeneity. The altered heme-protein contacts could be related to the enhanced oxygen affinity in the minor form.

Cisplatin versus cisplatin plus etoposide in the treatment of advanced non-small-cell lung cancer. Lung Cancer Working Party, Belgium.

We conducted a randomized study comparing the survival after treatment with cisplatin (120 mg/m2) or cisplatin plus etoposide (100 mg/m2 on days 1, 2, and 3) in 162 evaluable patients with advanced non-small-cell lung cancer (NSCLC). No statistically significant difference in survival was detected; the median survival was 26 and 22 weeks, respectively, for patients receiving cisplatin and for those receiving cisplatin plus etoposide. The objective response rate was 19% for cisplatin and 26% for the combination; the corresponding response rates were 17% and 43% in patients with limited disease. No significant differences were detected between the two study arms as far as toxicity was concerned, except for alopecia and granulocytopenia, which occurred more frequently in patients treated with cisplatin plus etoposide.

Phase III randomized trial comparing cisplatin and carboplatin with or without ifosfamide in patients with advanced non-small-cell lung cancer. European Lung Cancer Working Party.

PURPOSE: A phase III randomized trial in patients with advanced non-small-cell lung cancer (NSCLC) was performed to determine if the addition of ifosfamide to moderate-dose cisplatin and carboplatin improved response rate (primary end point) and survival. PATIENTS AND METHODS: A total of 529 patients were randomized to receive a combination of moderate-dose carboplatin (200 mg/m2 intravenously [i.v.] on day 1) and cisplatin (30 mg/m2 i.v. on days 2 and 3) with (CCI arm) or without (CC arm) ifosfamide (1.5 g/m2 i.v. on days 1 to 3). There were 248 eligible patients on the CC arm and 257 on the CCI arm, with 220 and 238 patients assessable for response, respectively. All but 23 had stage IV disease with pleural effusion. RESULTS: There was a 16% objective response (OR) rate to CC and a 31% OR rate to CCI. That observed difference was highly statistically significant (P < 0.001). Duration of response and survival were not statistically different between arms. The CCI regimen was associated with significantly more acute toxicities: emesis, alopecia, leukopenia, and thrombocytopenia. The frequency of chronic renal, auditive, and peripheral neurologic toxicity was low in both arms (4.6% and 6.6%, respectively, after six courses of chemotherapy). The relative dose-intensity (RDI) of the CCI arm was significantly lower than that of the CC arm. CONCLUSION: The addition of ifosfamide to moderate-dose cisplatin and carboplatin significantly improves the antitumoral response rate, but has no apparent effect an survival in advanced NSCLC.