Radiative neutron capture as a counting technique at pulsed spallation neutron sources: a review of current progress.

Neutron scattering techniques are attracting an increasing interest from scientists in various research fields, ranging from physics and chemistry to biology and archaeometry. The success of these neutron scattering applications is stimulated by the development of higher performance instrumentation. The development of new techniques and concepts, including radiative capture based neutron detection, is therefore a key issue to be addressed. Radiative capture based neutron detectors utilize the emission of prompt gamma rays after neutron absorption in a suitable isotope and the detection of those gammas by a photon counter. They can be used as simple counters in the thermal region and (simultaneously) as energy selector and counters for neutrons in the eV energy region. Several years of extensive development have made eV neutron spectrometers operating in the so-called resonance detector spectrometer (RDS) configuration outperform their conventional counterparts. In fact, the VESUVIO spectrometer, a flagship instrument at ISIS serving a continuous user programme for eV inelastic neutron spectroscopy measurements, is operating in the RDS configuration since 2007. In this review, we discuss the physical mechanism underlying the RDS configuration and the development of associated instrumentation. A few successful neutron scattering experiments that utilize the radiative capture counting techniques will be presented together with the potential of this technique for thermal neutron diffraction measurements. We also outline possible improvements and future perspectives for radiative capture based neutron detectors in neutron scattering application at pulsed neutron sources.

Cancer detection and management in patients with haemophilia: a retrospective European multicentre study.

Lymphomas or hepatocarcinomas related to blood-borne transmitted diseases are well-known malignancies in persons with haemophilia (PWH). However, rising life expectancy has increased the number of PWH suffering from other malignancies. This study aimed to collect cancer occurrence data in PWH followed in five European haemophilia treatment centres (Brussels, Geneva, Marseille, Montpellier and Paris-Bicêtre) over the last 10 years and to analyse some particular features of cancer occurring in PWH. In total, 45 malignancies were diagnosed in 1067 PWH. The most common malignancies were hepatocellular carcinoma (12/45) and urogenital tract tumours (9/45). Bleeding at presentation or changes in bleeding pattern was indicative of cancer in four patients. Three patients with mild haemophilia developed anti-factor VIII inhibitors after intensive substitution therapy prior to surgery or invasive procedures. There was no bleeding associated with chemotherapy or radiotherapy. A few bleeding complications occurred following invasive (3/39) or surgical procedures (2/27) as a result of insufficient hemostatic coverage or in spite of adequate substitution. No bleeding was noted after liver or prostate biopsies. Following cancer diagnosis, five patients were switched from on-demand to prolonged prophylaxis substitution. In the majority of cases, the standard cancer treatment protocol was not modified on account of concomitant haemophilia. Thus, oncological treatments are not contraindicated and should not be withheld in PWH assuming that adequate haemostasis correction is undertaken. As shown by our study results, a change in bleeding pattern in adult PWH should raise suspicion of a malignancy. Intensive substitution must be considered a risk factor for inhibitor development.

Short-term and mid-term outcome of total ankle replacement in haemophilic patients.

BACKGROUND: Ankle arthropathy is very frequent in haemophilic patients. Prostheses are valuable alternatives to arthrodesis in non-haemophilic patients. We report the experience of a single centre in France on the use of prostheses in haemophilic patients. METHODS: Retrospective study of 21 patients with haemarthropathy who underwent ankle arthroplasty (32 ankles), with additional surgery, if needed, from July 2002 to September 2009 (mean follow-up 4.4±1.7 years). The American Orthopaedic Foot and Ankle Society (AOFAS) ankle-hindfoot scale was used to evaluate pain, function, ankle mobility and alignment. RESULTS: The overall AOFAS score improved from 40.2±19.4 (pre-surgery) to 85.3±11.4 (post-surgery). The function score increased from 23.6±7.7 to 35.9±6.7 and dorsiflexion from 0.3°±5.0° to 10.3°±4.4°. Two patients underwent further ankle arthrodesis. On X-ray, both tibial and talar components were stable and correctly placed in all ankles. Alignment was good. CONCLUSION: Ankle arthroplasty is a promising alternative to arthrodesis in haemophilic patients.

Post-viral idiopathic purpura fulminans is associated with inherited thrombophilia and anti-cardiolipin antibodies.

Introduction: Idiopathic purpura fulminans (IPF) is a rare and severe coagulation disorder, associated with transient anti-protein S (anti-PS) antibodies in the context of post-viral infection such as varicella. Anti-protein S antibodies are frequently found in the context of varicella, in contrast with the rarity of IPF. Other factors such as anti-phospholipid antibodies (APL) and inherited thrombophilia may be associated with severe vascular complication. Method: This is an ancillary study of a French multicenter retrospective series and systematic review of literature. We analyzed patients who were tested for inherited thrombophilia, namely antithrombin, protein C, protein S deficiency; prothrombin gene G20210A polymorphism (FII:G20210A),Factor V R506Q polymorphism (FV:R506Q); and/or for APL (lupus anticoagulant (LA), anti-cardiolipin antibodies (ACL), or anti-beta 2-GPI antibodies (Aß2GP1). Results: Among the 25 patients tested for inherited thrombophilia, 7 (28%) had positive results. Three had FV R506Q, two FII:G20210A, one compound heterozygote FV:R506Q associated to FII:G20210A, and one protein C deficiency. APL testing was performed in 32 patients. It was positive in 19 patients (59%): 17 ACL (53%), 5 LA (16%), 4 Aß2GP1 (13%). The risk of severe complications was not associated with presence of inherited thrombophilia or APL presence, with RR: 0.8 [95% CI: 0.37-1.71], p = 1 and RR: 0.7 [95% CI: 0.33-1.51], p = 0.39, respectively. We found a high prevalence of inherited thrombophilia or APL in a population of patients with IPF. However, we do not find an association with the occurrence of severe vascular complications or venous thromboembolism.

Spherical momentum distribution of the protons in hexagonal ice from modeling of inelastic neutron scattering data.

The spherical momentum distribution of the protons in ice is extracted from a high resolution deep inelastic neutron scattering experiment. Following a recent path integral Car-Parrinello molecular dynamics study, data were successfully interpreted in terms of an anisotropic Gaussian model, with a statistical accuracy comparable to that of the model independent scheme used previously, but providing more detailed information on the three dimensional potential energy surface experienced by the proton. A recently proposed theoretical concept is also employed to directly calculate the mean force from the experimental neutron Compton profile, and to evaluate the accuracy required to unambiguously resolve and extract the effective proton potential from the experimental data.

MWCNT/rGO/natural rubber latex dispersions for innovative, piezo-resistive and cement-based composite sensors.

The present study is focused on the development and characterization of innovative cementitious-based composite sensors. In particular, multifunctional cement mortars with enhanced piezoresistive properties are realized by exploiting the concept of confinement of Multiwall Carbon Nanotubes (MWCNTs) and reduced Graphene Oxide (rGO) in a three-dimensional percolated network through the use of a natural-rubber latex aqueous dispersion. The manufactured cement-based composites were characterized by means of Inelastic Neutron Scattering to assess the hydration reactions and the interactions between natural rubber and the hydrated-cement phases and by Scanning Electron Microscopy and X-Ray diffraction to evaluate the morphological and mineralogical structure, respectively. Piezo-resistive properties to assess electro-mechanical behavior in strain condition are also measured. The results show that the presence of natural rubber latex allows to obtain a three-dimensional rGO/MWCNTs segregate structure which catalyzes the formation of hydrated phases of the cement and increases the piezo-resistive sensitivity of mortar composites, representing a reliable approach in developing innovative mortar-based piezoresistive strain sensors.

Author Correction: Egyptian metallic inks on textiles from the 15th century BCE unravelled by non-invasive techniques and chemometric analysis.

An amendment to this paper has been published and can be accessed via a link at the top of the paper.

Egyptian metallic inks on textiles from the 15th century BCE unravelled by non-invasive techniques and chemometric analysis.

The development of black inks has enabled writing to become an established method of communication in history. Although a large research effort has been devoted to the study of pigments and dyes used in ancient Egypt to decorate burial walls and furnishings, or to write on papyrus, to date little attention has been paid to the nature and technology of inks used on ritual and daily-use textiles, which may have fostered the transfer of metallic ink technology onto papyrus and parchment supports. We report about inks from 15th century BCE Egyptian textiles by combining non-invasive techniques, including ultraviolet (UV) reflected imaging, near-infrared reflectography (NIRR), X-ray fluorescence (XRF) spectroscopy, Raman spectroscopy and prompt-gamma-activation-analysis (PGAA). It is argued that the inks are related to the family of iron gall inks, whose introduction is commonly attributed to the third century BCE. This interpretation frames the technology of writing on fabrics, used by the ancient Egyptians, in a different time, thus providing new information on the genesis of mordant inks in the ancient Mediterranean cultures. We anticipate our study to be a starting point for further and more sophisticated investigations of textiles, which will clarify the origin of metallic ink in the ancient world.

First analysis of ancient burned human skeletal remains probed by neutron and optical vibrational spectroscopy.

Burned skeletal remains are abundant in archaeological and paleontological sites, the result of fire or of ancient funerary practices. In the burning process, the bone matrix suffers structural and dimensional changes that interfere with the reliability of available osteometric methods. Recent studies showed that these macroscopic changes are accompanied by microscopic variations are reflected in vibrational spectra. An innovative integrated approach to the study of archaeological combusted skeletal remains is reported here, where the application of complementary vibrational spectroscopic techniques-INS (inelastic neutron scattering), FTIR (Fourier transform infrared), and micro-Raman-enables access to the complete vibrational profile and constitutes the first application of neutron spectroscopy to ancient bones. Comparison with data from modern human bones that were subjected to controlled burning allowed identification of specific heating conditions. This pioneering study provides archaeologists and anthropologists with relevant information on past civilizations, including regarding funerary, burial, and cooking practices and environmental settings.

Combination of Coenzyme Q10 Intake and Moderate Physical Activity Counteracts Mitochondrial Dysfunctions in a SAMP8 Mouse Model.

Aging skeletal muscles are characterized by a progressive decline in muscle mass and muscular strength. Such muscular dysfunctions are usually associated with structural and functional alterations of skeletal muscle mitochondria. The senescence-accelerated mouse-prone 8 (SAMP8) model, characterized by premature aging and high degree of oxidative stress, was used to investigate whether a combined intervention with mild physical exercise and ubiquinol supplementation was able to improve mitochondrial function and preserve skeletal muscle health during aging. 5-month-old SAMP8 mice, in a presarcopenia phase, have been randomly divided into 4 groups (n = 10): untreated controls and mice treated for two months with either physical exercise (0.5 km/h, on a 5% inclination, for 30 min, 5/7 days per week), ubiquinol 10 (500 mg/kg/day), or a combination of exercise and ubiquinol. Two months of physical exercise significantly increased mitochondrial damage in the muscles of exercised mice when compared to controls. On the contrary, ubiquinol and physical exercise combination significantly improved the overall status of the skeletal muscle, preserving mitochondrial ultrastructure and limiting mitochondrial depolarization induced by physical exercise alone. Accordingly, combination treatment while promoting mitochondrial biogenesis lowered autophagy and caspase 3-dependent apoptosis. In conclusion, the present study shows that ubiquinol supplementation counteracts the deleterious effects of physical exercise-derived ROS improving mitochondrial functionality in an oxidative stress model, such as SAMP8 in the presarcopenia phase.

[Thromboembolic disease in pediatric oncology]. / La maladie thrombo-embolique veineuse en oncologie pédiatrique.

The survival rate of children with cancer is now close to 80 %, as a result of continuous improvement in diagnostic and treatment procedures. Prevention and treatment of treatment-associated complications is now a major challenge. Thromboembolic venous disease, due to multifactorial pathogenesis, is a frequent complication (up to 40 % asymptomatic thrombosis in children with cancer), responsible for significant morbidity. Predominantly in children with acute lymphoblastic leukemia, lymphoma, or sarcoma, thromboembolic disease justifies primary prophylaxis in certain populations at risk, whether genetic or environmental. The curative treatment, well codified, is based on the administration of low-molecular-weight heparin. In the absence of robust pediatric prospective studies, this article proposes a concise decision tree summarizing the preventive and curative strategy.

Fibrin clot structure in patients with congenital dysfibrinogenaemia.

The clinical phenotype of patients with congenital dysfibrinogenaemia is highly heterogeneous, from absence of symptoms to mild bleeding, or thrombosis. A few mutations are associated with a specific phenotype, but generally the clinical course is not predictable. We investigated whether fibrin clot properties are correlated with the patient's phenotype and/or genotype. Ex vivo plasma fibrin clot characteristics, including turbidity, fibrinolysis, clot permeability and fibrin fibre density assessed by laser scanner confocal microscopy were investigated in 24 genotyped patients with congenital dysfibrinogenaemia compared to normal pool plasma. Compared to normal pool plasma, the patients were characterised by slower fibrin polymerisation (lag time, 345.10 ± 22.98 vs. 166.00s), thinner fibrin fibres (maximum absorbance, 0.15 ± 0.01 vs. 0.31), prolonged clot lysis time (23.72 ± 0.97 vs. 20.32 min) and larger clot pore size (21.5×10(-9) ± 4.48×10(-9) vs. 7.96×10(-9)cm(2)). Laser scanning confocal microscopy images confirmed disorganised fibrin networks in all patients. Patients with tendency to bleed showed an increased permeability compared to asymptomatic patients (p=0.01) and to patients with a thrombotic history (p=0.02) while patients with thrombotic history had a tendency to have a prolonged clot lysis time. Fibrin clot properties were similar among hotspot mutations. Further studies including a larger number of patients are needed to evaluate whether analysis of permeability and clot lysis time may help to distinguish the clinical phenotype in these patients and to assess differences according to the genotype.

Virtual unrolling and deciphering of Herculaneum papyri by X-ray phase-contrast tomography.

A collection of more than 1800 carbonized papyri, discovered in the Roman 'Villa dei Papiri' at Herculaneum is the unique classical library survived from antiquity. These papyri were charred during 79 A.D. Vesuvius eruption, a circumstance which providentially preserved them until now. This magnificent collection contains an impressive amount of treatises by Greek philosophers and, especially, Philodemus of Gadara, an Epicurean thinker of 1st century BC. We read many portions of text hidden inside carbonized Herculaneum papyri using enhanced X-ray phase-contrast tomography non-destructive technique and a new set of numerical algorithms for 'virtual-unrolling'. Our success lies in revealing the largest portion of Greek text ever detected so far inside unopened scrolls, with unprecedented spatial resolution and contrast, all without damaging these precious historical manuscripts. Parts of text have been decoded and the 'voice' of the Epicurean philosopher Philodemus is brought back again after 2000 years from Herculaneum papyri.

Immunonephelometric determination of fibrinogen on citrated or heparinized plasma: comparison with functional Clauss method.

BACKGROUND: Fibrinogen is routinely determined by functional assay on citrated plasma in the hematology department. However, immunoassay can be performed easily with nephelometric analyzer in the clinical chemistry laboratory allowing automatization. The aim of this study was first to compare the clotting von Clauss method (activity assay) with an immunonephelometric method (antigen assay) on the BN ProSpec (Dade Behring). Moreover, we evaluated the possibility of collecting blood samples on heparin to facilitate blood collection for clinicians and reduce required blood collection volumes for dosages. METHODS: In a first step of experiment, the accuracy of immunonephelometric analytical performance was tested on heparinized and citrated tubes. For comparison studies, fibrinogen activity was then determined on citrated tubes in the hematology department and antigen measurement was performed on both citrated and heparinized plasma from 130 consecutive patients. RESULTS: As a result, the immunonephelometric method shows reliable performance and clinical sample measurements are not affected by the method used, validating the use of heparinized plasma samples for fibrinogen antigen determination with Dade Behring reagents.

Evolution of Hydrogen Dynamics in Amorphous Ice with Density.

The single-particle dynamics of hydrogen atoms in several of the amorphous ices are reported using a combination of deep inelastic neutron scattering (DINS) and inelastic neutron scattering (INS). The mean kinetic energies of the hydrogen nuclei are found to increase with increasing density, indicating the weakening of hydrogen bonds as well as a trend toward steeper and more harmonic hydrogen vibrational potential energy surfaces. DINS shows much more pronounced changes in the O-H stretching component of the mean kinetic energy going from low- to high-density amorphous ices than indicated by INS and Raman spectroscopy. This highlights the power of the DINS technique to retrieve accurate ground-state kinetic energies beyond the harmonic approximation. In a novel approach, we use information from DINS and INS to determine the anharmonicity constants of the O-H stretching modes. Furthermore, our experimental kinetic energies will serve as important benchmark values for path-integral Monte Carlo simulations.

[Carriers of haemophilia: Experience of a French university hospital]. / Conductrices d'hémophilie: expérience d'un CHRU en France.

OBJECTIVES: To report the management of carriers of haemophilia in a French university hospital and assess different issues of these patients. PATIENTS AND METHODS: Retrospective study of the carriers of haemophilia who consulted at the university hospital of Montpellier, France, between 1995 and 2011. Information were obtained from medical records and from a questionnaire sent to carriers. We recorded data about biological characteristics, bleeding tendency and management of pregnancies. RESULTS: Sixty-four carriers of haemophilia A or B were included. Their median FVIII or FIX level was 52 % (range, 15-137 %). Menstrual bleeding lasted more than 7 days in 31 % of carriers. A total of 142 pregnancies started in 54 carriers, and 101 resulted in live births with 26 boys with haemophilia. Sixty-two prenatal diagnoses carried out, 15 have terminated their pregnancy because of a hemophiliac male fetus. Seventy-six percent of deliveries were vaginal delivery and 49 % took place in a level-3 maternity. There were 10.8 % and 8.5 % primary and secondary post-partum hemorrhage, respectively. CONCLUSION: The risk of bleeding among carriers of haemophilia is associated with their antihemophilic factor level. To improve the management of carriers, a multidisciplinary and standardized medical record, with a specific questionnaire to evaluate bleedings, could be considered. A regional register that lists all carriers, regardless of their antihemophilic factor level, would also be useful.

Cytokine-mediated regulation of ovarian function: interleukin-1 inhibits gonadotropin-induced androgen biosynthesis.

Resident ovarian macrophages have long been recognized as potential in situ regulators of ovarian function, presumably through local paracrine secretion of regulatory molecules (i.e. cytokines). One such macrophage product, interleukin-1 (IL-1) has recently been shown to exert profound regulatory effects at the level of the ovarian granulosa cell. In this report, we examine the possibility that the adjacent theca-interstitial (androgen-producing) cell may also be a site of IL-1 reception and action. The basal accumulation of androsterone, the major androgenic steroid synthesized by whole ovarian dispersates from immature rats, in the presence of insulin (1 microgram/ml), increased 8- to 9-fold after treatment with human CG (1 ng/ml). Although IL-1 alpha or IL-1 beta (10 ng/ml) by themselves were without effect on basal androsterone accumulation, both cytokines (IL-1 beta greater than IL-1 alpha) inhibited human CG hormonal action (in the presence of insulin) in a dose-dependent manner, the maximal inhibitory effect being 75%. Similar results were obtained when using highly purified theca-interstitial cells derived from the same animal model suggesting that IL-1-attenuated androgen biosynthesis is due, at least in part, to IL-1 acting directly at the level of the theca-interstitial cells. The IL-1 effect proved relatively specific since all other known interleukins (IL-1, IL-3, IL-4, IL-5, and IL-6) were without effect. Moreover, IL-1 beta action was effectively immunoneutralized when concurrently applied with anti-IL-1 beta (but not nonimmune) sera. Significantly, the antigonadotropic action of IL-1 could not be accounted for by a decrease in the viable cell mass. Tracer studies with radiolabeled steroid substrates suggested that IL-1-attenuated ovarian androsterone accumulation is due, if only in part, to inhibition of transformations catalyzed by (theca-interstitial) 17 alpha-hydroxylase/17:20 lyase, stimulation of theca-interstitial (or granulosa 20 alpha-hydroxysteroid dehydrogenase-mediated conversions, or both. Taken together, these findings indicate that relatively low concentrations of IL-1, possibly originating from somatic ovarian cells or resident ovarian macrophages, are capable of exerting an inhibitory effect upon gonadotropin-supported androgen production. As such, these and previous observations suggest that intraovarian IL-1 may play a dual regulatory role in the developing ovarian follicle by targeting both the granulosa and theca-interstitial cells as its sites of action.

Analysis of the genotypes and phenotypes of 37 unrelated patients with inherited factor VII deficiency.

Severe inherited factor VII (FVII) deficiency is a rare autosomal recessive disorder with a poor relationship between FVII coagulant activity and bleeding tendency. Both clinical expression and mutational spectrum are highly variable. We have screened for mutations the FVII gene of 37 unrelated patients with a FVII coagulant activity less than 5% of normal pooled plasmas. The nine exons with boundaries and the 5' flanking region of the FVII gene were explored using a combination of denaturing gradient gel electrophoresis and direct DNA sequencing. This strategy allowed us to characterise 68 out of the 74 predicted FVII mutated alleles. They corresponded to a large panel of 40 different mutations. Among these, 18 were not already reported. Genotypes of the severely affected patients comprised, on both alleles, deleterious mutations which appeared to be related to a total absence of activated FVII. We suggest that this absence of functional FVII can explain the severe clinical expression. Whether a small release of FVII is sufficient to initiate the coagulation cascade and to prevent the expression of a severe phenotype, requires further investigations.

Effect of gonadotropins, insulin and IGF I on granulosa luteal cells from polycystic ovaries.

The aim of this work is to evaluate the gonadotropin and growth factor effects in vitro on steroidal response in human granulosa luteal cells from polycystic ovaries compared with normal granulosa luteal cells in humans. The granulosa cells from polycystic (polycystic ovarian granulosa cells, POGC) and normo-ovulating women (normal cells, NC) were collected in the preovulatory phase after oocyte retrieval during the GIFT program. The cells were cultured serum-free for 24, 48 and 96 h. Estradiol and progesterone production was determined with or without HCG (1-200 ng/ml), FSH (10-300 ng/ml), insulin (1-50 micrograms/ml) and IGF I (1-50 ng/ml) addition. All treatments significantly induced a 2-3 fold estradiol increase at the 48-h and 96-h time points in POGC. The progesterone production was unaffected by HCG, FSH, insulin and IGF I addition, respectively, in POGC, whereas the NC were responsive at the 48-h and 96-h time points. FSH did not stimulate progesterone production in granulosa cells either from polycystic or normovulating subjects. Our findings indicate that POGC are hypersensitive to all substances in terms of estradiol production, whereas they show a reduced capacity of progesterone production with some treatments.