Spectral unmixing applied to fast identification of γ-emitting radionuclides using NaI(Tl) detectors.

Spectral unmixing was investigated for fast spectroscopic identification in γ-emitter mixtures at low-statistics in the case of measurements performed to prevent illegal nuclear material trafficking or for in situ environmental analysis following a radiological or nuclear accident. For that purpose, a multiplicative update algorithm based on full-spectrum analysis was tested in the case of a 3″x3″ NaI(Tl) detector. Automatic decision-making was addressed using Monte Carlo calculations of decision thresholds and detection limits. The first results obtained with a portable instrument equipped with a 3″x3″ NaI(Tl) detector designed for the control of food samples by non-expert users following a radiological or nuclear accident, are also presented.

Activity measurements and determination of nuclear decay data of 166Ho in the MRTDosimetry project.

Holmium-166 is a high-energy ß--emitter radionuclide (~ 1.8 MeV) with a short half-life (~26.8h) that offers great potential as an alternative to 90Y for the treatment of liver cancer based on radioembolization. The possibility of quantitative Single Photon Emission Computed Tomography (SPECT) imaging of the main γ-ray emission at 80.6 keV, in addition to strong paramagnetic properties suitable for Magnetic Resonance Imaging (MRI), complement this therapeutic potential. The present paper describes the measurements carried out in three European radionuclide metrology laboratories for primary standardization of 166Ho and new determinations of X- and γ-ray photon-emission intensities in the framework of the European EMPIR project MRTDosimetry. New half-life measurements were also performed.

A new bunya-like virus associated with mass mortality of white-clawed crayfish in the wild.

We report the discovery of a new enveloped, spherical virus belonging to the Phenuiviridae family of negative ssRNA viruses associated with a massive outbreak in a French population of the endangered white-clawed crayfish Austropotamobius pallipes. We call this virus Bunya-like Brown Spot Virus (BBSV) and characterize it using transmission electronic microscopy, genome sequencing and clinical signs. Infected specimens show discolored brown spots on the cuticle. Using RNA-seq data we assembled a partial sequence for the L, M and S genome segments of BBSV. Phylogenetic analyses using all three segments show this virus is closely related to the Wenling crustacean virus 7 (China) and to a bunya-like virus found in feces of the European otter. Our survey of the mass mortality event indicates the virus is less virulent than the crayfish plague caused by Aphanomyces astaci. Overall, the discovery of BBSV provides a new important asset to monitor A. pallipes populations.

A novel GPR55-mediated satiety signal in the oval Bed Nucleus of the Stria Terminalis.

Nestled within feeding circuits, the oval (ov) region of the Bed Nucleus of the Stria Terminalis (BNST) may be critical for monitoring energy balance through changes in synaptic strength. Here we report that bidirectional plasticity at ovBNST GABA synapses was tightly linked to the caloric state of male rats, seesawing between long-term potentiation (iLTP, fed) and depression (iLTD, food restricted). L-α-lysophosphatidylinositol (LPI) acting on GPR55 receptors and 2-arachidonoylglycerol (2-AG) through CB1R were respectively responsible for fed (iLTP) and food restricted (iLTD) states. Thus, we have characterized a potential gating mechanism within the ovBNST that may signal metabolic state within the rat brain feeding circuitry.

Standardization of 68Ge/68Ga using the 4πß-γ coincidence method based on Cherenkov counting.

In the framework of an international BIPM comparison (Bureau International des Poids et Mesures), the activity standardization of 68Ge in a solution of 68Ge/68Ga in equilibrium provided by NIST was carried out at LNHB. This exercise was organized to meet the growing interest in 68Ga as a radiopharmaceutical in nuclear medicine services (e.g. as a surrogate of 18F for PET imaging). Due to the volatility of germanium, the activity standardization of 68Ge was investigated at LNHB by means of 4πß-γ coincidence counting based on Cherenkov measurements. This technique was applied to take advantage of the Cherenkov threshold (~ 260keV in aqueous solutions) in order to prevent counting from electron-capture events associated with 68Ge disintegrations. Cherenkov counting was performed using glass and polyethylene vials and the resulting activity concentrations were compared with 4πß-γ coincidence measurements based on liquid scintillation. The efficiency-extrapolation curve obtained with Cherenkov measurements in glass vials was compared to Monte Carlo simulations based on the Geant4 code.

CHRODIS criteria applied to the MASK (MACVIA-ARIA Sentinel NetworK) Good Practice in allergic rhinitis: a SUNFRAIL report.

A Good Practice is a practice that works well, produces good results, and is recommended as a model. MACVIA-ARIA Sentinel Network (MASK), the new Allergic Rhinitis and its Impact on Asthma (ARIA) initiative, is an example of a Good Practice focusing on the implementation of multi-sectoral care pathways using emerging technologies with real life data in rhinitis and asthma multi-morbidity. The European Union Joint Action on Chronic Diseases and Promoting Healthy Ageing across the Life Cycle (JA-CHRODIS) has developed a checklist of 28 items for the evaluation of Good Practices. SUNFRAIL (Reference Sites Network for Prevention and Care of Frailty and Chronic Conditions in community dwelling persons of EU Countries), a European Union project, assessed whether MASK is in line with the 28 items of JA-CHRODIS. A short summary was proposed for each item and 18 experts, all members of ARIA and SUNFRAIL from 12 countries, assessed the 28 items using a Survey Monkey-based questionnaire. A visual analogue scale (VAS) from 0 (strongly disagree) to 100 (strongly agree) was used. Agreement equal or over 75% was observed for 14 items (50%). MASK is following the JA-CHRODIS recommendations for the evaluation of Good Practices.

A general dead-time correction method based on live-time stamping. Application to the measurement of short-lived radionuclides.

Dead-time correction formulae are established in the general case of superimposed non-homogeneous Poisson processes. Based on the same principles as conventional live-timed counting, this method exploits the additional information made available using digital signal processing systems, and especially the possibility to store the time stamps of live-time intervals. No approximation needs to be made to obtain those formulae. Estimates of the variances of corrected rates are also presented. This method is applied to the activity measurement of short-lived radionuclides.

Work productivity in rhinitis using cell phones: The MASK pilot study.

Allergic rhinitis often impairs social life and performance. The aim of this cross-sectional study was to use cell phone data to assess the impact on work productivity of uncontrolled rhinitis assessed by visual analogue scale (VAS). A mobile phone app (Allergy Diary, Google Play Store and Apple App Store) collects data from daily visual analogue scales (VAS) for overall allergic symptoms (VAS-global measured), nasal (VAS-nasal), ocular (VAS-ocular) and asthma symptoms (VAS-asthma) as well as work (VAS-work). A combined nasal-ocular score is calculated. The Allergy Diary is available in 21 countries. The app includes the Work Productivity and Activity Impairment Allergic Specific Questionnaire (WPAI:AS) in six EU countries. All consecutive users who completed the VAS-work from 1 June to 31 October 2016 were included in the study. A total of 1136 users filled in 5818 days of VAS-work. Symptoms of allergic rhinitis were controlled (VAS-global <20) in approximately 60% of the days. In users with uncontrolled rhinitis, approximately 90% had some work impairment and over 50% had severe work impairment (VAS-work >50). There was a significant correlation between VAS-global calculated and VAS-work (Rho=0.83, P<0.00001, Spearman's rank test). In 144 users, there was a significant correlation between VAS-work and WPAI:AS (Rho=0.53, P<0.0001). This pilot study provides not only proof-of-concept data on the work impairment collected with the app but also data on the app itself, especially the distribution of responses for the VAS. This supports the interpretation that persons with rhinitis report both the presence and the absence of symptoms.

Drug usage patterns and treatment costs in newly-diagnosed type 2 diabetes mellitus cases, 2007 vs 2012: findings from a large US healthcare claims database analysis.

Objective To explore trends in demographics, comorbidities, anti-diabetic drug usage, and healthcare utilization costs in patients with newly-diagnosed type 2 diabetes mellitus (T2DM) using a large US claims database. Methods For the years 2007 and 2012, Truven Health Marketscan Research Databases were used to identify adults with newly-diagnosed T2DM and continuous 12-month enrollment with prescription benefits. Variables examined included patient demographics, comorbidities, inpatient utilization patterns, healthcare costs (inpatient and outpatient), drug costs, and diabetes drug claim patterns. Results Despite an increase in the overall database population between 2007-2012, the incidence of newly-diagnosed T2DM decreased from 1.1% (2007) to 0.65% (2012). Hyperlipidemia and hypertension were the most common comorbidities and increased in prevalence from 2007 to 2012. In 2007, 48.3% of newly-diagnosed T2DM patients had no claims for diabetes medications, compared with 36.2% of patients in 2012. The use of a single oral anti-diabetic drug (OAD) was the most common diabetes medication-related claim (46.2% of patients in 2007; 56.7% of patients in 2012). Among OAD monotherapy users, metformin was the most commonly used and increased from 2007 (74.7% of OAD monotherapy users) to 2012 (90.8%). Decreases were observed for sulfonylureas (14.1% to 6.2%) and thiazolidinediones (7.3% to 0.6%). Insulin, predominantly basal insulin, was used by 3.9% of patients in 2007 and 5.3% of patients in 2012. Mean total annual healthcare costs increased from $13,744 in 2007 to $15,175 in 2012, driven largely by outpatient services, although costs in all individual categories of healthcare services (inpatient and outpatient) increased. Conversely, total drug costs per patient were lower in 2012 compared with 2007. Conclusions Despite a drop in the rate of newly-diagnosed T2DM from 2007 to 2012 in the US, increased total medical costs and comorbidities per individual patient suggest that the clinical and economic trends for T2DM are not declining.

Calculation of extrapolation curves in the 4π(LS)ß-γ coincidence technique with the Monte Carlo code Geant4.

At LNE-LNHB, a liquid scintillation (LS) detection setup designed for Triple to Double Coincidence Ratio (TDCR) measurements is also used in the ß-channel of a 4π(LS)ß-γ coincidence system. This LS counter based on 3 photomultipliers was first modeled using the Monte Carlo code Geant4 to enable the simulation of optical photons produced by scintillation and Cerenkov effects. This stochastic modeling was especially designed for the calculation of double and triple coincidences between photomultipliers in TDCR measurements. In the present paper, this TDCR-Geant4 model is extended to 4π(LS)ß-γ coincidence counting to enable the simulation of the efficiency-extrapolation technique by the addition of a γ-channel. This simulation tool aims at the prediction of systematic biases in activity determination due to eventual non-linearity of efficiency-extrapolation curves. First results are described in the case of the standardization (59)Fe. The variation of the γ-efficiency in the ß-channel due to the Cerenkov emission is investigated in the case of the activity measurements of (54)Mn. The problem of the non-linearity between ß-efficiencies is featured in the case of the efficiency tracing technique for the activity measurements of (14)C using (60)Co as a tracer.

The endocannabinoid system within the dorsal lateral geniculate nucleus of the vervet monkey.

The endocannabinoid system mainly consists of cannabinoid receptors type 1 (CB1R) and type 2 (CB2R), their endogenous ligands termed endocannabinoids (eCBs), and the enzymes responsible for the synthesis and degradation of eCBs. These cannabinoid receptors have been well characterized in rodent and monkey retinae. Here, we investigated the expression and localization of the eCB system beyond the retina, namely the first thalamic relay, the dorsal lateral geniculate nucleus (dLGN), of vervet monkeys using immunohistochemistry methods. Our results show that CB1R is expressed throughout the dLGN with more prominent labeling in the magnocellular layers. The same pattern is observed for the degradation enzyme, fatty acid amide hydrolase (FAAH). However, the synthesizing enzyme N-acyl-phosphatidylethanolamine phospholipase D (NAPE-PLD) is expressed homogenously throughout the dLGN with no preference for any of the layers. These proteins are weakly expressed in the koniocellular layers. These results suggest that the presence of the eCB system throughout the layers of the dLGN may represent a novel site of neuromodulatory action in normal vision. The larger amount of CB1R in the dLGN magnocellular layers may explain some of the behavioral effects of cannabinoids associated with the integrity of the dorsal visual pathway that plays a role in visual-spatial localization and motion perception.

Determination of reference values for optical properties of liquid phantoms based on Intralipid and India ink.

A multi-center study has been set up to accurately characterize the optical properties of diffusive liquid phantoms based on Intralipid and India ink at near-infrared (NIR) wavelengths. Nine research laboratories from six countries adopting different measurement techniques, instrumental set-ups, and data analysis methods determined at their best the optical properties and relative uncertainties of diffusive dilutions prepared with common samples of the two compounds. By exploiting a suitable statistical model, comprehensive reference values at three NIR wavelengths for the intrinsic absorption coefficient of India ink and the intrinsic reduced scattering coefficient of Intralipid-20% were determined with an uncertainty of about 2% or better, depending on the wavelength considered, and 1%, respectively. Even if in this study we focused on particular batches of India ink and Intralipid, the reference values determined here represent a solid and useful starting point for preparing diffusive liquid phantoms with accurately defined optical properties. Furthermore, due to the ready availability, low cost, long-term stability and batch-to-batch reproducibility of these compounds, they provide a unique fundamental tool for the calibration and performance assessment of diffuse optical spectroscopy instrumentation intended to be used in laboratory or clinical environment. Finally, the collaborative work presented here demonstrates that the accuracy level attained in this work for optical properties of diffusive phantoms is reliable.

First TDCR measurements at low energies using a miniature x-ray tube.

Developed for radionuclide standardization using liquid scintillation, the Triple to Double Coincidence Ratio (TDCR) method is applied using coincidence counting obtained with a specific three-photomultiplier system. For activity determination, a statistical model of light emission is classically used to establish a relation between the detection efficiency and the experimental TDCR value. At LNE-LNHB, a stochastic approach of the TDCR modeling was developed using the Monte Carlo code Geant4. The interest of this TDCR-Geant4 model is the possibility to simulate the propagation of optical photons from their creation in the scintillation vial to the production of photoelectrons in photomultipliers. As an alternative to the use of radionuclide sources, first TDCR measurements are presented using a miniature x-ray tube closely coupled to the scintillation vial. The objective of this new set-up was to enable low-energy depositions (lower than 20 keV) in liquid scintillator in order to study the influence of both time and geometrical dependence between PMTs already observed with radioactive sources. As for the statistical TDCR model, the non-linearity of light emission is implemented in the TDCR-Geant4 model using the Birks formula which depends on the kB factor and the scintillation yield. Measurements performed with the x-ray tube are extended to the assessment of these parameters and they are tested afterwards in the TDCR-Geant4 model for activity measurements of (3)H.

Improved real-world glycaemic outcomes with liraglutide versus other incretin-based therapies in type 2 diabetes.

AIM: Liraglutide (LIRA) once-daily has provided greater A1C reductions than either exenatide (EXEN) twice-daily or sitagliptin (SITA) once-daily in head-to-head trials. The objective of this analysis is to compare the real-world clinical effectiveness of these agents in the USA. METHODS: Using the IMS Health (Alexandria, VA, USA) integrated claims database, A1C outcomes in patients aged ≥ 18 years with type 2 diabetes (T2D) who initiated either LIRA, EXEN or SITA (including SITA/metformin) were retrospectively compared. Patients included in the analysis had ≥ 1 prescription for LIRA, EXEN or SITA between January and December 2010 (index period) and persisted with their index treatment regimens for 6 months post-index. Outcomes included changes in A1C from baseline (45 days pre-index through 7 days post-index) to follow-up [6 months post-index (± 45)] and the proportion of patients reaching A1C<7%. Multivariable regression models adjusted for confounding factors (e.g. age, comorbidities, baseline A1C and background antidiabetic therapy). RESULTS: The predicted change in A1C from baseline was greater for LIRA patients compared with both SITA (-1.08 vs. -0.68%; treatment difference 0.40%, p < 0.0001) and EXEN (-1.08 vs. -0.75%; treatment difference 0.32%, p < 0.001). Predicted A1C goal achievement, derived from the multivariate logistic regression model, was higher with LIRA compared with both SITA [64.4% (95% confidence interval, CI: 63.5-65.3) vs. 49.4% (95% CI: 48.5-50.4); p < 0.0001] and EXEN [64.4% (95% CI: 63.5-65.3) vs. 53.6% (95% CI: 52.6-54.6); p < 0.0001]. CONCLUSIONS: In clinical practice, LIRA was associated with significantly greater reductions in A1C and improved glycaemic goal attainment compared with either EXEN or SITA among adult patients with T2D.

Digital pulse processing and optimization of the front-end electronics for nuclear instrumentation.

This article describes an algorithm developed for the digital processing of signals provided by a high-efficiency well-type NaI(Tl) detector used to apply the 4πγ technique. In order to achieve a low-energy threshold, a new front-end electronics has been specifically designed to optimize the coupling to an analog-to-digital converter (14 bit, 125 MHz) connected to a digital development kit produced by Altera(®). The digital pulse processing is based on an IIR (Infinite Impulse Response) approximation of the Gaussian filter (and its derivatives) that can be applied to the real-time processing of digitized signals. Based on measurements obtained with the photon emissions generated by an (241)Am source, the energy threshold is estimated to be equal to ~2 keV corresponding to the physical threshold of the NaI(Tl) detector. An algorithm developed for a Silicon Drift Detector used for low-energy x-ray spectrometry is also described. In that case, the digital pulse processing is specifically designed for signals provided by a reset-type preamplifier ((55)Fe source).

Involvement of cannabinoid receptors in peripheral and spinal morphine analgesia.

The interactions between the cannabinoid and opioid systems for pain modulation are reciprocal. However, the role and the importance of the cannabinoid system in the antinociceptive effects of opioids remain uncertain. We studied these interactions with the goal of highlighting the involvement of the cannabinoid system in morphine-induced analgesia. In both phases of the formalin test, intra paw and intrathecal morphine produced similar antinociceptive effects in C57BL/6, cannabinoid type 1 and type 2 receptor wild-type (respectively cnr1WT and cnr2WT) mice. In cnr1 and cnr2 knockout (KO) mice, at the dose used the antinociceptive effect of intra paw morphine in the inflammatory phase of the formalin test was decreased by 87% and 76%, respectively. Similarly, the antinociceptive effect of 0.1µg spinal morphine in the inflammatory phase was abolished in cnr1KO mice and decreased by 90% in cnr2KO mice. Interestingly, the antinociceptive effect of morphine in the acute phase of the formalin test was only reduced in cnr1KO mice. Notably, systemic morphine administration produced similar analgesia in all genotypes, in both the formalin and the hot water immersion tail-flick tests. Because the pattern of expression of the mu opioid receptor (MOP), its binding properties and its G protein coupling remained unchanged across genotypes, it is unlikely that the loss of morphine analgesia in the cnr1KO and cnr2KO mice is the consequence of MOP malfunction or downregulation due to the absence of its heterodimerization with either the CB1 or the CB2 receptors, at least at the level of the spinal cord.

Chemokines mediate ethanol-induced exacerbations of murine cockroach allergen asthma.

Asthma imposes considerable patient and economic burdens, with the most severe cases causing the greatest affliction. Identifying stimuli that worsen asthma severity is an essential step to controlling both disease morbidity and the lessening economic impact. This study provides the first mechanistic investigation into how acute ethanol exposure will increase asthma severity in a murine model of mild cockroach allergen (CRA)-induced asthma. Outbred mice were sensitized to induce mild allergic asthma, with intratracheal CRA exposures on days 0 and 14. On day 21 mice were gavaged with water or 32% ethanol, and the third allergen exposure was given 30 min post-gavage. Asthmatic responses were measured at several time-points up to 42 h after the third allergen challenge. Ethanol-gavaged mice showed increased asthma severity within 90 min post-allergen challenge, with exacerbations lasting for 24 h. Ethanol caused greater airways obstruction, including an eightfold increase in epithelial cell mucin and increased mucus plugs, resulting in a 50% reduction in bronchiole patency. Ethanol gavage also induced significant increases in airways hyperreactivity. While T helper type 1 (Th1) and Th2 cytokines were not altered by ethanol gavage, pulmonary neutrophil and eosinophil recruitment were augmented. This increase was associated with increased chemokine production. Administration 2 h prior to ethanol gavage of a neutralizing antibody cocktail to keratinocyte-derived chemokine, macrophage inflammatory protein-2, eotaxin-1 and eotaxin-2 prevented ethanol-induced eosinophil recruitment and airways hyperreactivity. These data provide evidence that acute alcohol exposure immediately prior to a mild allergen-triggered asthmatic episode will exacerbate asthma severity mediated by increased production of chemokines.

["It was me or them!": the no exit escape of a future author of psychotic double parricide]. / « C'était eux ou moi ! ¼ : la fuite sans issue d'un futur auteur de double parricide psychotique.

CASE-REPORT: H. had perceived his father as an evil persecutor ever since his adolescence. He developed paranoid schizophrenia of persecution in which his father occupied the main role. Little by little, in his desperate resistance against his father, perceived as his enemy, he acquired such a feeling of prejudice, of violation of his personality, and of impotence that the only way out was to escape in order to survive. At the age of 18, he decides to run away from home and from France to stop suffering. He goes to Canada and later to the USA where he would stay 9 years, during which his madness does not stop. Wherever he goes, he always feels the presence of his father in his head: "He orders me, he criticizes me from a distance, he steals all my thoughts, he is in charge of my actions, he takes away the bread from my mouth to humiliate me and kill me…" Thanks to his marginal lifestyle, he maintains a relative adaptation, a fragile equilibrium in his existential bubble in which he doesn't tolerate any breaking and entering. His delusion of prejudices and persecution, of which the main character had always been his father, extends to include society in general, cornering and leading the subject to commit an offense as a reaction of irrepressible pathological self-defense. He is questioned by the police, taken to prison and later taken to an American psychiatric hospital, after shooting at those whom he thinks are "CIA agents" (who are actually people forcing him to move the boat in which he lives). After being deported back to France, he returns to his parent's home, the source of all his madness. During the following months, he lives locked up in his room afraid of being near his father and tormented by his delirious ideas. In order to stop his suffering, he decides to buy a fire-arm to kill himself. One day, his father, accompanied by his mother, break into his room. He takes the rifle hidden under the mattress, and kills his father at point blank. "I thought that I had instantly killed my father, because he fell face down on the ground. On the other hand, my mother remained standing while my sister, screaming, escaped through the window of the living room. My mother, injured on her right side, moved back to the living room. Seeing that my mother hadn't fallen to the ground and not wanting to make her suffer, I reloaded my rifle. I took out the cartridge, and reloaded the rifle with a cartridge of buckshot. It seemed to me that she was still standing in front of the couch. I fired the gun a second time without looking and at that moment she falls on the couch… dead… She is the enemy because she is my father's wife". DISCUSSION: The recounting and analysis of this double psychotic parricide case illustrate the psychopathologic constants and criminal dynamic that are most often present in this type of crime. The constants are the following: the perpetrator of the post-adolescence or adult parricide is often a psychotic young man; he/she lives a long, delusional story in which one or both parents have an important role; this insane delusion leads to suffering and/or to identifiable behavioral problems that together can constitute a criminal psychic state; The homicidal reaction takes place right after one or a group of factors (such as an argument, brawl, a fit of delusion, interruption of the therapeutic treatment…) that are set off in the criminal pathological state. These psychopathological constants, if they conjoin, are also the factors and indicators of danger. They should be considered as a warning sign to take preventive and remedial measures.

Diversity of ARSACS mutations in French-Canadians.

BACKGROUND: The growing number of spastic ataxia of Charlevoix-Saguenay (SACS) gene mutations reported worldwide has broadened the clinical phenotype of autosomal recessive spastic ataxia of Charlevoix-Saguenay (ARSACS). The identification of Quebec ARSACS cases without two known SACS mutation led to the development of a multi-modal genomic strategy to uncover mutations in this large gene and explore phenotype variability. METHODS: Search for SACS mutations by combining various methods on 20 cases with a classical French-Canadian ARSACS phenotype without two mutations and a group of 104 sporadic or recessive spastic ataxia cases of unknown cause. Western blot on lymphoblast protein from cases with different genotypes was probed to establish if they still expressed sacsin. RESULTS: A total of 12 mutations, including 7 novels, were uncovered in Quebec ARSACS cases. The screening of 104 spastic ataxia cases of unknown cause for 98 SACS mutations did not uncover carriers of two mutations. Compounds heterozygotes for one missense SACS mutation were found to minimally express sacsin. CONCLUSIONS: The large number of SACS mutations present even in Quebec suggests that the size of the gene alone may explain the great genotypic diversity. This study does not support an expanding ARSACS phenotype in the French-Canadian population. Most mutations lead to loss of function, though phenotypic variability in other populations may reflect partial loss of function with preservation of some sacsin expression. Our results also highlight the challenge of SACS mutation screening and the necessity to develop new generation sequencing methods to ensure low cost complete gene sequencing.