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Background Anal ulcerations are frequently observed in Crohn’s disease (CD). Their natural history remains poorly known, especially in pediatric-onset CD. The aims of this study were: to determine in a population-based study the risk of anal ulcerations in pediatric onset CD; to identify risk factors for anal ulcerations; to evaluate the risk of progression towards suppurative lesions; to evaluate the risk factors of progression towards suppurative lesions. Methods All patients with a diagnosis of CD before the age of 17 years between 1988 and 2011 within the population-based registry EPIMAD were followed retrospectively until 2013. A specific collection of additional data was performed in patients with anal ulcerations at diagnosis or during follow-up. The variables collected included: proctological examination, diagnostic management (perineal MRI, endoscopic ultrasound, examination under general anaesthesia) and treatment (medical or surgical). Multivariate Cox models were used to identify factors associated with anal ulcerations and factors of progression towards suppurative lesions. An adjusted time-dependent Cox model was used to evaluate the risk of progression of anal ulcerations towards suppurative lesions. Results 1005 patients were included (females, 450 (44.8%); median age at diagnosis 14.4 years (IQR, 12.0–16.1)). 257 (25.6%) had anal ulceration at diagnosis. Cumulative incidence of anal ulceration at 5 and 10 years from diagnosis was 38.4% (CI95%, 35.2–41.4) and 44.0% (CI95%, 40.5–47.2). The presence of extra-intestinal manifestations (HR 1.46, CI95% 1.19–1.80, p=0.0003) and upper digestive location (HR 1.51, CI95% 1.23–1.86, p In patients with anal ulceration, the diagnostic period (before or since the “biologic era”), exposure to immunosuppressants and/or anti-TNF did not influence the risk of perianal suppuration. Conclusion Anal ulceration is frequent in pediatric-onset CD, with nearly half of patients presenting with at least one episode after 10 years of evolution. Perianal suppurations are twice as frequent in patients with present or past anal ulceration. These results plead for a proactive therapeutic approach in case of anal ulcerations.

Correction for ‘Tuning trion binding energy and oscillator strength in a laterally finite 2D system: CdSe nanoplatelets as a model system for trion properties’ by Sabrine Ayari et al., Nanoscale, 2020, 12, 14448–14458, DOI: 10.1039/D0NR03170D.

In this paper, a high-power ultrawideband antenna is presented for the purpose of remotely neutralizing improvised explosive devices. The developed antenna has a bandwidth between 230 MHz and 2 GHz, as well as a maximum realized gain of 18.7 dB. The antenna structure incorporates a solid dielectric (HDPE 1000) so that it can be powered, without risk of a possible breakdown voltage, by a Marx generator which delivers a bipolar pulse with a peak amplitude of +/−250 kV, a rise time of 170 ps, and a duration of 1 ns. The radiated electric field obtained in simulation is, respectively, 1 MV/m peak and 126 kV/m peak at a distance of 1 m and 10 m.

International audience; Highly pure millimeter-sized MOF-5 single crystals were synthesized and characterized. Photoluminescence (PL) spectroscopy and time-correlated single photon counting (TCSPC) demonstrate a solvent-guest dependency of MOF-5 emission and its ligand-centred nature. These results allowmeasuring the true MOF-5 luminescence free of solvent at a wavelength of 355 nm, a significantly lower wavelength than previously published. MOF-5 emission was also evaluated with different solvents and various degrees of water intake, explaining previously published observations. Comparison between lifetimes shows the fluorophore stabilization within the frameworks and demonstrates the progressive influence of the Zn4O subunits on the fluorescence during hydration. Overall, this work highlights the necessity to obtain phase-pure material, especially when moisture sensitivity can play a role, before ascribing electronic transitions. This study is a rigorous new take on the iconic MOF-5 and on its photoluminescence properties.

Background Anti-TNFs antibodies are the first biologic treatment option in inflammatory bowel disease (IBD). The long-term effectiveness of this strategy at the population level is poorly known, particularly in pediatric-onset IBD. Methods All patients diagnosed with Crohn’s disease (CD) or ulcerative colitis (UC) before the age of 17 between 1988 and 2011 in a population-based registry were followed retrospectively until 2013. Among patients treated with anti-TNFs, the cumulative probabilities of anti-TNF failure defined by primary failure, loss of response or intolerance were evaluated. Factors associated with anti-TNF failure were investigated by a Cox model. Results Among a total of 1007 patients with CD (median disease duration, 3.2 years IQR (1.2–7.6) and median follow-up 8.8 years (IQR, 4.6–14.2)) and 337 patients with UC (median disease duration, 2.5 years IQR [1.1–4.5] and median follow-up 7.2 years (IQR, 3.8–13.0)), respectively 481 (48%) and 81 (24%) were treated with anti-TNFs. Median age at anti-TNF initiation was 17.4 years (IQR, 15.1–20.9). Median duration of anti-TNF therapy was 20.4 months (IQR, 6.0–59.9). In CD, the probability of failure of 1st line anti-TNF therapy at 1, 3 and 5 years was respectively 29.3%, 47.0% and 54.6% for infliximab (n = 397) and 22.6%, 37.7% and 48.0% for adalimumab (n = 83). In UC, the probability of failure of 1st line anti-TNF therapy at 1, 3 and 5 years was respectively 37.3%, 49.0% and 61.0% for infliximab (n = 71) and 12.5% for these 3 timepoints for adalimumab (n = 10). In CD, probabilities of primary failure, loss of response and intolerance at 5 years were 10.4%, 36.7% and 6.8% (n = 480), respectively; in UC, these same probabilities were 7.5%, 39.2% and 11.3% (n = 81), respectively. Female sex (Hazard Ratio (HR) 1.43, 95% CI 1.09–1.87; p = 0.010) and intestinal resection prior anti-TNF initiation (HR 1.73, 95% CI 1.21–2.47, p = 0.003) were associated with anti-TNF failure in multivariate analysis. Conclusion In a population-based study of pediatric-onset IBD, approximately half of anti-TNFs users discontinue use within 5 years. Loss of response account for around two-thirds of failure, both for CD and UC.

In the past few years, several protocols have been reported on the synthesis of CdSe nanoplatelets with narrow photoluminescence (PL) spectrum, high PL quantum efficiency, and short exciton lifetime. The corresponding core/shell nanoplatelets are however still mostly based on CdSe/CdS, which possess an extended lifetime and a strong red shift of the band-edge absorption and emission, in accordance with a quasi-type-II band alignment. Here we report on a robust synthesis procedure to grow a ZnS shell around CdSe nanoplatelets at moderate temperatures of 100–150 °C, to improve the optical properties of CdSe nanoplatelets via a type-I core/shell heterostructure. The shell growth is performed under ambient atmosphere, in either toluene or 1,2-dichlorobenzene. The variation of the shell thickness induces a continuous red shift of the PL peak, eventually reaching 611 nm. The PL quantum efficiency is increased compared to the original CdSe cores, with values up to 60% depending on the shell thickness. High-resolution transmission electron microscopy reveals a bending of the nanoplatelets caused by strain due to 12% lattice mismatch between CdSe and ZnS. The present procedure can easily be translated to other core/shell nanocrystals, such as CdSe/CdS and CdSe/CdZnS nanoplatelets. The present publication is realized with the support of the Ministero degli Affari Esteri e della Cooperazione Internazionale (IONX-NC4SOL). This project has also received funding from the European Union’s Horizon 2020 research and innovation program under Grant Agreement No. 696656 (GrapheneCore1). J.L.M. acknowledges support from UJI project P1-1B2014-24 and MINECO project CTQ2014-60178-P.

We present a theoretical study combined with experimental validations demonstrating that CdSe nanoplatelets are a model system to investigate the tunability of trions and excitons in laterally finite 2D semiconductors. Our results show that the trion binding energy can be tuned from 36 meV to 18 meV with the lateral size and decreasing aspect ratio, while the oscillator strength ratio of trions to excitons decreases. In contrast to conventional quantum dots, the trion oscillator strength in a nanoplatelet at low temperature is smaller than that of the exciton. The trion and exciton Bohr radii become lateral size tunable,e.g.from similar to 3.5 to 4.8 nm for the trion. We show that dielectric screening has strong impact on these properties. By theoretical modeling of transition energies, binding energies and oscillator strength of trions and excitons and comparison with experimental findings, we demonstrate that these properties are lateral size and aspect ratio tunable and can be engineered by dielectric confinement, allowing to suppresse.g.detrimental trion emission in devices. Our results strongly impact further in-depth studies, as the demonstrated lateral size tunable trion and exciton manifold is expected to influence properties like gain mechanisms, lasing, quantum efficiency and transport even at room temperature due to the high and tunable trion binding energies.

Colloidal two-dimensional (2D) nanoplatelet heterostructures are particularly interesting as they combine strong confinement of excitons in 2D materials with a wide range of possible semiconductor junctions due to a template-free, solution-based growth. Here, we present the synthesis of a ternary 2D architecture consisting of a core of CdSe, laterally encapsulated by a type-I barrier of CdS, and finally a type-II outer layer of CdTe as so-called crown. The CdS acts as a tunneling barrier between CdSe- and CdTe-localized hole states, and through strain at the CdS/CdTe interface, it can induce a shallow electron barrier for CdTe-localized electrons as well. Consequently, next to an extended fluorescence lifetime, the barrier also yields emission from CdSe and CdTe direct transitions. The core/barrier/crown configuration further enables two-photon fluorescence upconversion and, due to a high nonlinear absorption cross section, even allows to upconvert three near-infrared photons into a single green photon. These results demonstrate the capability of 2D heterostructured nanoplatelets to combine weak and strong confinement regimes to engineer their optoelectronic properties.

International audience; Since Helium-3 shortage announcement, organic scintillators play a major role in neutron detection. Our laboratory decided to focus on plastic scintillators and their ability to discriminate fast neutrons from gamma rays. In this work, we highlight the influence of the secondary fluorophore in lab-made plastic scintillators. The secondary fluorophore is generally added in the scintillating mixture to shift the emission wavelength towards the transparency domain of the material to improve its attenuation length. Thus, it is considered as a harmless molecule and is barely seen as a key criterion that could enhance the performances of the organic scintillator. In our work, we demonstrate that this molecule, even added at a small concentration (typically in the range 0.02–0.2 wt%), directly impacts the neutron/gamma discrimination ability of plastics. Not only the secondary fluorophore plays a role in self-absorption of the scintillating material, but also the couple it creates with the primary fluorophore has to be carefully chosen, as some specific triplet energy transfers between the two fluorophores can influence the neutron/gamma discrimination abilities of the plastic scintillator. Aside from classical photophysical inconveniences such as self-absorption or diffusion, the possibility that the whole, bulk material was heterogeneous in a photochemical point of view was also checked. Thus, various samples were cut from bulk monoliths and their pulse shape discrimination compared with the parent scintillator in terms of Figure of Merit and light output.

CdSe nanoplatelets can be synthesized with different lateral sizes; very small nanoplatelets have almost quantum dot like features (almost discrete exciton states), while very large ones are expected to have properties of colloidal quantum wells (exciton continuum). However, nanoplatelets can be in an intermediate confinement regime with a rich substructure of excitons, which is neither quantum dot like nor an ideal 2D exciton. In this manuscript, we discuss the experimental transition energies and relaxation dynamics of exciton states in CdSe platelets with varying lateral dimensions and compare them with a microscopic theoretical model including exciton-phonon scattering. The model takes special care of the interplay of confinement and Coulomb coupling in the intermediate regime showing strong changes with respect to simple weak or strong confinement models by solving the full four dimensional lateral factorization free exciton wavefunction. Depending on the platelet size broad resonances previously attributed to just ground and excited states are actually composed of a rich substructure of several exciton states in their temporal dynamics. We show that these factorization free exciton states can explain the spectral features observed in photoluminescence experiments. Furthermore we demonstrate that the interplay of exciton bright and dark states provides principle insights into the overall temporal relaxation dynamics, and allows tuning of the exciton cooling via lateral platelet size. Our results and theoretical approach are directly relevant for understanding e.g. the size tuneability of lasing, excitonic cooling dynamics or light harvesting applications in these and similar 2D systems of finite lateral size.

International audience; In the field of nuclear physics, plastic scintillators are popular and efficient radiation detectors thanks to the following properties: they can be prepared in large volumes, are cheap and various configurations can be afforded to the material. However, peculiar applications might require plastic scintillator with unusual scintillation decay times, such as laser beam positioning or detectors stacking. In the case of the scintillation decay time, commercial suppliers do not propose many choices, as only the range 0.7–10 ns is usually covered, along with a longer decay time – 285 ns – material. Herein we propose a new concept and associated formulations where the scintillation decay time can be finely chosen and tuned in a range starting at 2.5 ns and finishing around 90 ns. These materials are presented, synthesized and characterized.

We report for the first time severe acute pancreatitis in a child treated for phenylketonuria (PKU) discovered on neonatal screening. This 2-year-old boy was first hospitalized for bilious vomiting and moderate back pain. Laboratory values included a lipase level of 1.142 U/L, a phenylalanine level of 10mg/dL, and computed tomography revealed Balthazar grade E pancreatitis. Continuous enteral feeding was started on the 3rd day after admission. We observed clinical and biological improvement. Etiologic investigations for pancreatitis returned negative. Despite the severity of the pancreatitis, we did not observe decompensation of the metabolic disease. Specific nutritional management was necessary.

In a comparative study we investigate the carrier-phonon coupling in CdSe based core-only and hetero 2D as well as 0D nanoparticles. We demonstrate that the coupling can be strongly tuned by the lateral size of nanoplatelets, while, due to the weak lateral confinement, the transition energies are only altered by tens of meV. Our analysis shows that an increase in the lateral platelet area results in a strong decrease in the phonon coupling to acoustic modes due to deformation potential interaction, yielding an exciton deformation potential of 3.0 eV in line with theory. In contrast, coupling to optical modes tends to increase with the platelet area. This cannot be explained by Fröhlich interaction, which is generally dominant in II-VI materials. We compare CdSe/CdS nanoplatelets with their equivalent, spherical CdSe/CdS nanoparticles. Universally, in both systems the introduction of a CdS shell is shown to result in an increase of the average phonon coupling, mainly related to an increase of the coupling to acoustic modes, while the coupling to optical modes is reduced with increasing CdS layer thickness. The demonstrated size and CdS overgrowth tunability has strong implications for applications like tuning carrier cooling and carrier multiplication - relevant for solar energy harvesting applications. Other implications range from transport in nanosystems e.g. for field effect transistors or dephasing control. Our results open up a new toolbox for the design of photonic materials.

International audience; The Trillat procedure performed as open surgery to treat anterior shoulder instability has been proven effective in preventing recurrences and restoring range of motion. An arthroscopically assisted variant of the Trillat procedure is described here, together with the preliminary clinical results in 18 patients treated between 2011 and 2014. After a mean follow-up of 24.7±9.8 months, the clinical outcomes were very satisfactory, with a Walch-Duplay score of 81.5±18.0, a Rowe score of 83.6±16.0, and 94% of satisfied or very satisfied patients. Mean operative time was 55±13min. No recurrences were recorded. As an easily performed procedure that provides good clinical outcomes, the arthroscopically assisted Trillat procedure is a simple and reproducible alternative to arthroscopic Latarjet procedure, which is still reserved for highly experienced surgical teams.

International audience; In this paper we consider aggregation technique to reduce the complexity of large-scale traffic network. In particular, we consider the city of Grenoble and show that, by clustering adjacent sections based on a similarity of speed condition, it is possible to cut down the complexity of the network without loosing crucial and intrinsic information. To this end, we consider travel time computation as a metric of comparison between the original graph and the reduced one: for each cluster we define four attributes (average speed, primary and secondary length and heading) and show that, in case of an aggregation rate of 95%, these attributes are sufficient in order to maintain the travel time error below the 25%.

We report herein the application of a new series of plastic scintillators loaded with lithium tetraborate nanoparticles (Li 2 B 4 O 7 ) designed for the simultaneous detection of fast neutrons, thermal neutrons and gamma-rays. First, MCNP simulations are performed to highlight the potential benefit of Li 2 B 4 O 7 loading. Then, a nanoparticle-loaded scintillator is prepared and evaluated towards the detection of a partially thermalized neutron/gamma 252-californium source. Several scenarios of radiation/matter interactions are evaluated against the observed results. A detection chamber composed of boron-containing chipboard wood has been specifically designed and a subtraction method was set up to afford the best discrimination pattern. For the first time, a triple discrimination is presented with a nanoparticles-loaded plastic scintillator, where both 6 Li(n, α ) and 10 B(n, α ) signatures are observed. A Figure of Merit of 1.40 was calculated between fast neutrons and gamma rays around 480 keVee. The Figure of Merit between fast + thermal neutrons and gamma rays is slightly worse as it is 1.16 at 380 keVee.

We report the synthesis and characterization of covalent organic frameworks (COFs) incorporating thiophene-based building blocks. We show that these are amenable to reticular synthesis, and that bent ditopic monomers, such as 2,5-thiophenediboronic acid, are defect-prone building blocks that are susceptible to synthetic variations during COF synthesis. The synthesis and characterization of an unusual charge transfer complex between thieno[3,2- b ]thiophene-2,5-diboronic acid and tetracyanoquinodimethane enabled by the unique COF architecture is also presented. Together, these results delineate important synthetic advances toward the implementation of COFs in electronic devices.

International audience; The synthesis, photophysical properties, and applications in scintillation counting of N-(2-ethylhexyl)carbazole (EHCz) are reported. This molecule displays all of the required characteristics for an efficient liquid scintillator (emission wavelength, scintillation yield), and can be used without any extra fluorophores. Thus, its scintillation properties are discussed, as well as its fast neutron/gamma discrimination. For the latter application, the material is compared with the traditional liquid scintillator BC-501 A, and other liquid fluorescent molecules classically used as scintillation solvents, such as xylene, pseudocumene (PC), linear alkylbenzenes (LAB), diisopropylnaphthalene (DIN), 1-methylnaphthalene (1-MeNapht), and 4-isopropylbiphenyl (iPrBiph). For the first time, an excimeric form of a molecule has been advantageously used in scintillation counting. A moderate discrimination between fast neutrons and gamma rays was observed in bulk EHCz, with an apparent neutron/gamma discrimination potential half of that of BC-501 A.

We evidence excited state emission from p states well below ground state saturation in CdSe nanoplatelets. Size-dependent exciton ground and excited state energies and population dynamics are determined by four independent methods: time-resolved PL, time-integrated PL, rate equation modeling, and Hartree renormalized k·p calculations-all in very good agreement. The ground state-excited state energy spacing strongly increases with the lateral platelet quantization. Depending on its detuning to the LO phonon energy, the PL decay of CdSe platelets is governed by a size tunable LO phonon bottleneck, related to the low exciton-phonon coupling, very large oscillator strength, and energy spacing of both states. This is, for instance, ideal to tune lasing properties. CdSe platelets are perfectly suited to control the exciton-phonon interaction by changing their lateral size while the optical transition energy is determined by their thickness.

This study used a novel computational pipelin e to exploit draft bacterial genome sequenc es in order to predict, automatically andrapidly, PCR primer sets for Dickeya spp. that were unbiased in terms of diagnostic g ene choice. This pipeline was applied to 16draft and four complete Dickeya genome sequences to generate >700 primer sets predicted to discriminate between Dickeya atthe species level. Predicted diagnostic primer sets for both D. dianthicola (DIA-A and DIA-B) and ‘ D. solani’ (SOL-C and SOL-D)were validated against a panel of 70 Dickeya reference strains, representative of the known diversity of this genus, to confirmprimer specificity. The classification of the f our previously sequenced strains was re-exa mined and evidence of possible misclassifi-cation of three of these strains is presented.Keywords: diagnostics, Erwinia spp., Pectobacterium spp., potato, real-time PCR

This paper presents the design and experimental results of a hand-portable, self-contained, and repetitive radiation source of high-power ultrawideband (UWB) pulses. This source consists of a deployed UWB antenna driven by a high-pulsed power (HPP) generator and powered by a self-contained 50-kV rapid charger at repetition rates up to 100 Hz. By changing the HPP generator, two different electric wave shapes with two different frequency spectra can be generated. Each HPP generator is based on the use of a repetitive Marx generator. On the one hand, a 200-kV/1.4-J Marx generator is associated with a coaxial pulse-forming stage consisting of two highly pressurized spark gap switches and a Blumlein line, which produces bipolar pulses. Its main characteristics are an output voltage of +100 kV/-100 kV and a pulsewidth of 1.5 ns. On the other hand, we have developed a second eight-stage Marx generator, where the pulse-forming stage is the last stage of the structure. It delivers pulses in the 150-kV/1-J range, with a fall time of 300 ps and an 850-ps pulse duration. Electrical signals are radiated by a deployed Valentine antenna. It is a new traveling wave antenna that is designed to radiate high-voltage repetitive pulses with the challenge of high gain and low dispersion in an extremely restricted volume. The design of a rapid charging power supply is also presented, meeting stringent package constraints while still enabling high repetition rates. It has already demonstrated its capability of charging, from a dc power battery, a 5-nF capacitance up to 50 kV in 5 ms at a 100-Hz repetition rate for some bursts of thousand pulses. The autonomy is more than 35 000 shots (depending on the number of battery packs inside). Electric field measurements were performed on the whole package to determine the figure of merit (the maximum value of far-field peak electric field strength multiplied by the distance) of the UWB source in each configuration (bipolar and monopolar sets). The figure of merit measured is 200 kV for both.

Correction for ‘Understanding the behaviour of different metals in loaded scintillators: discrepancy between gadolinium and bismuth’ by Guillaume H. V. Bertrand et al., J. Mater. Chem. C, 2015, 3, 6006.

Conference of 4th International Conference on Advancements in Nuclear Instrumentation Measurement Methods and their Applications, ANIMMA 2015 ; Conference Code:121554; International audience; Recent developments of plastic scintillators are reviewed, from January 2000 to June 2015. All examples are distributed into the main application, i.e. how the plastic scintillator was modified to enhance the detection towards a given radiation particle. The main characteristics of these newly created scintillators and their detection properties are given.

Generation of unipolar and bipolar pulses by using high- and medium-voltage silicon rectifier diodes is achieved. These components are provided by the French Atomic Energy Commission (CEA). Furthermore, these devices work in the linear mode of photoconducting switches. Generation of electrical unipolar pulses with an amplitude of 10.7 kV and a full-width at half-maximum of 300 ps by using only 1.2 mJ of optical power is demonstrated. This energy value is 10-100 times less than usually published during the past decades. Furthermore, the linear mode running of these devices permits to synchronize several generators with a precision as low as 2 ps. This low timing jitter is useful for bipolar generators in order to control their spectrum with high precision, i.e., bipolar pulses of 3 kV peak-to-peak have been generated with a cycle duration of 400 ps and an optical energy of 1 mJ

Summary. In medical and social surveys a large number of multiply correlated explanatory variables are often investigated for their relationship with an outcome variable for which a cause is sought. In initial pairwise comparisons between the explanatory variable and the explained variable, one of the explanatory variables may stand out as the most significantly related in such comparisons. It may be, however, that this variable is innocently implicated as a causative variable because of its correlation with all the other explanatory variables. Although statisticians are well aware of such phenomena, members in other professions such as the medical, legal, administrative and political professions find it difficult to comprehend. It is difficult for statisticians to convince them of such effects. With simple thinking it appears so obvious to implicate as a prime cause that explanatory variable which is most highly correlated with an outcome variable. To demonstrate this phenomenon a data set has been constructed. In this data set the outcome variable appears to be most strongly associated with the first explanatory variable. A multiple-regression analysis, however, shows that the first explanatory variable has no effect. Moreover, the other explanatory variables together account for a greater proportion of the explained variation than does the first explanatory variable. Similar results are likely to arise using other statistical analysis techniques such as analyses of variance, of covariance, of generalized linear models, of categorical data and of survival data. It will be of considerable help to the statistics profession to be able to illustrate the phenomenon with examples such as the example that is presented here. The implications for statistical analysis of large surveys may lead to questioning the validity of the results of some surveys where the results may appear to be blindingly obvious.

International audience; We describe an efficient synthetic route toward novel organocobalt complexes [([small eta]4-C4(nT)4)Co([small eta]5-C5H5)] with n = 1, 2, 3 thiophene rings. Solution-processed bulk heterojunctions solar cells based on CpCoCb(3T)4:PCBM blends achieve power conversion efficiencies of up to 2.1%.

The molecular basis of familial hypercholesterolemia (FH) in three families of Spanish descent from La Habana was investigated by the candidate gene approach. The Arg3500Gln mutation of apolipoprotein B-100 was not found. Identification of low density lipoprotein receptor (LDLR) gene haplotypes segregating with FH guided the characterisation of three point mutations by automated sequencing. One, a Val408-->Met missense mutation, a founder mutation in Afrikaner FH patients, was recurrent, being associated with a distinct DNA haplotype. The other two, Glu256-->Lys and Val776-->Met missense mutations, were novel and modified highly conserved residues. These mutations were absent in normolipidemic subjects and were associated in heterozygous carriers with twice the cholesterol levels observed in non-carriers. Noticeably, cardiovascular complications were rarely observed in older heterozygotes, even in those with the Afrikaner FH-2 mutation. These findings confirm the molecular heterogeneity of LDLR gene mutations causing FH and the variability of their expression across different populations.

Purpose To compare the rates of change in the visual field (VF) in patients with glaucoma before and after trabeculectomy. Methods 52 eyes of 52 patients over 35 years of age with different types of chronic glaucoma who underwent primary trabeculectomy were evaluated retrospectively. Pre- and postoperative automated visual fields measured by the same technique were compared to detect differences in rates of progression. Rates of VF loss before and after trabeculectomy were calculated using global indices, mean defect (MD) and pattern standard deviation (PSD) and linear regression analysis per cluster. Linear mixed models were used to compare the evolution of the VF before and after trabeculectomy. Results The mean follow-up period pre-trabeculectomy was 3.88 years (min 0.92, max 10.72) and post-trabeculectomy 3.82 years (min 2.03, max 8.02). The intraocular pressure (IOP) decreased significantly from 18.12 ± 4.71 mmHg before trabeculectomy to 11 ± 2.87 mmHg at the last follow-up after trabeculectomy (P < 0.0001). The rate of progression of MD decreased with 55%, from –0.36 dB/year before surgery to –0.16 dB/year after surgery (P = 0.15). The rates of progression of PSD decreased from –1.69 dB/year before to –0.018 dB/year after surgery (P = 0.03). Of the 10 predefined clusters, only in cluster 10, situated infero-temporally, the difference between the slopes was statistically significant (0.64 dB/year, P = 0.0021). Conclusion Trabeculectomy significantly decreased the rates of glaucomatous VF progression.

Recently, LGE and XLIM Laboratories initiated collaboration on high-power microwave (HPM) transient radiation source conception. Ultra-wideband (UWB) antennas have been originally designed for UWB radar demonstrators. These prototypes have been built to support high-voltage (HV) short duration pulses with a 25 kV amplitude. Because of its high gain and its capability to radiate short pulses without dispersion within the 300 MHz-2.5 GHz frequency band, a type of these UWB antennas, the Valentine Antenna, has been chosen to be the radiating element of two new high-power HV UWB sources. This antenna, originally designed for low voltage, is made of two curved metallic strips and a copper coaxial-to-strip transition with a classical N connector. Some modifications were achieved in order to improve the dielectric strength of the antenna. Consequently, it is now able to radiate pulses delivered by HV (up to 300 kV), few hundreds hertz, subnanosecond transient sources. Initially, a 3-D model of the antenna was first computed with a time-domain electromagnetic software so as to study the influence of these modifications on the radiating element main characteristics. Then, frequency and transient domains studies were realised. Presented results demonstrate that the antenna S 11 parameter remains relatively unchanged and that in the entire frequency band, gain is 1 dB lower than the expected value with the original low-voltage design. This new HV antenna and its main radiation characteristics are described.

Thermolysis of [bis(diisopropylamino)phosphanyl](trimethylsilyl)diazomethane 1 affords the corresponding carbene 2, which is stable enough to be spectroscopically characterized. This species possesses a phosphorus–carbon multiple-bond character as shown by the 2 + 3 and 2 + 2 cycloaddition reactions observed with trimethylsilyl azide or N2O and ethyl cyanoformate, respectively. On the other hand, 2 undergoes all the classical reactions of a carbene: cyclopropanation reaction with electron-poor alkenes, carbon–hydrogen bond insertion, and carbene–carbene coupling with isonitriles. Compound 2 reacts with trimethylsilyl triflate affording a stable methylenephosphonium salt 15. Treatment of the lithium salt of the [bis(diisopropylamino)thiophosphoranyl]diazomethane 18 with the bis(diisopropylamino)phosphanyl chloride leads to a stable nitrilimine 3. Thermolysis of 3 affords the isomeric diazo derivative 20, while photolysis gives rise to thiophophoranylnitrile 21 and cyclodiphosphazene 23. Regioselective 2 + 3 cycloadditions are observed with electron-poor dipolarophiles. Addition of trimethylsilyl triflate to 3 leads to a stable electrophilic nitrilimine 29.

We present in this paper the design and realisation of two autonomous, ultra wideband radiation sourcesconsisting of a high gain broadband antenna driven by two subnanosecond pulsed power sources. Each one ismade of a Marx generator and a pulse forming device based on the use of gaseous spark gap. The main pulsedsource is a ten stage subnanosecond Marx generator which delivers pulses in the range of 250 kV/1.5 J, with a300 ps rise time, subnanosecond pulse duration at a pulse repetition frequency of 350 Hz. The antenna combinedwith the pulsed source is a travelling wave antenna called Valentine antenna. Some mechanical modiflcations weremade to improve the dielectric strength of this radiation element. A 3D model of the antenna, on a time domainelectromagnetic software, was flrst performed to study the in°uence of these modiflcations on the main radiatingcharacteristics of the antenna. Its high gain and its capability to radiate short pulses without dispersion allow usto achieve a high measured flgure of merit.PACS numbers: 84.70.+p, 07.57.Hm, 84.30.Ng

1. The toxic effects of nonsteroidal anti-inflammatory drugs for the lower gastrointestinal tract share certain features with inflammatory processes, suggesting that the release of inflammation cytokines such as TNF-alpha may damage the intestine. 2. Rats received a s.c. injection of indomethacin. Then, jejunum-ileum was taken up for the quantification of ulcerations, production of TNF-alpha, nitrites and PGE2 ex vivo and activity of calcium-independent NO synthase and myeloperoxydase. Activation of NO metabolism and myeloperoxydase were measured as potential effectors of TNF-alpha. 3. Jejunum-ileum from rats having received indomethacin (10 mg kg(-1)) produced TNF-alpha ex vivo. Cytokine production was associated with the onset of macroscopic ulcerations of the small intestine, and preceded nitrite production and tissue activity of myeloperoxidase. 4. Similar intestinal ulcerations and upregulation of TNF-alpha were obtained with flurbiprofen (30 mg kg(-1)), chemically unrelated to indomethacin. 5. TNF-alpha production was proportional to the indomethacin dose (from 3-20 mg kg(-1)) and correlated with the surface area of ulcerations and nitrite production, 24 h after indomethacin administration. 6. Pretreatment of rats with RO 20-1724, a type-IV phosphodiesterase inhibitor which inhibits TNF-alpha synthesis, substantially reduced jejunum-ileum ulcerations, TNF-alpha and nitrite production and tissue enzyme activities. 7. These findings provide evidence that TNF-alpha is increased in indomethacin-induced intestinal ulcerations and support suggestions that TNF-alpha is involved at an early stage of nonsteroidal anti-inflammatory drug toxicity for the small intestine.

We analysed the frequency of p53 mRNA overexpression in a series of 109 primary colorectal carcinomas and its association with p53 gene mutation, which has been correlated with short survival. Sixty-nine of the 109 cases (63%) demonstrated p53 mRNA overexpression, without any correlation with stage or site of disease. Comparison with p53 gene mutation indicated that, besides cases in which p53 gene mutation and p53 mRNA overexpression were either both present (40 cases) or both absent (36 cases), there were also cases in which p53 mRNA was overexpressed in the absence of any mutation (29 cases) and those with a mutant gene in which the mRNA was not overexpressed (four cases). Moreover, the mutant p53 tumours exhibited an increase of p53 mRNA expression, which was significantly higher in tumours expressing the mutated allele alone than in tumours expressing both wild- and mutated-type alleles. These data (1) show that p53 mRNA overexpression is a frequent event in colorectal tumours and is not predictive of the status of the gene, i.e. whether or not a mutation is present; (2) provide further evidence that p53 protein overexpression does not only result from an increase in the half-life of mutated p53 and suggest that inactivation of the p53 function in colorectal cancers involves at least two distinct mechanisms, including p53 overexpression and/or mutation; and (3) suggest that p53 mRNA overexpression is an early event, since it is not correlated with Dukes stage.

The mode of Pneumocystis carinii transmission is controversial. Recent studies point to exogenous inoculation rather than reactivation, and person-to-person transmission has also been suggested. Comparison of nucleotide sequences of the large-subunit mitochondrial rRNA gene of P. carinii from human immunodeficiency virus-seropositive patients showed strain differences.