High-energy acceleration phenomena in extreme-radiation-plasma interactions.

We simulate, using a particle-in-cell code, the chain of acceleration processes at work during the Compton-based interaction of a dilute electron-ion plasma with an extreme-intensity, incoherent γ-ray flux with a photon density several orders of magnitude above the particle density. The plasma electrons are initially accelerated in the radiative flux direction through Compton scattering. In turn, the charge-separation field from the induced current drives forward the plasma ions to near-relativistic speed and accelerates backwards the nonscattered electrons to energies easily exceeding those of the driving photons. The dynamics of those energized electrons is determined by the interplay of electrostatic acceleration, bulk plasma motion, inverse Compton scattering and deflections off the mobile magnetic fluctuations generated by a Weibel-type instability. The latter Fermi-like effect notably gives rise to a forward-directed suprathermal electron tail. We provide simple analytical descriptions for most of those phenomena and examine numerically their sensitivity to the parameters of the problem.

Development of a 3D-printed bioabsorbable composite scaffold with mechanical properties suitable for treating large, load-bearingarticular cartilage defects.

Extracellular matrix (ECM) biomaterials have shown promise for treating small artucular-joint defetcs. However, ECM-based biomaterials generally lack appropriate mechanical properties to support physiological loads and are prone to delamination in larger cartilage defects. To overcome these common mechanical limitations, a collagen hyaluronic-acid (CHyA) matrix, with proven regenerative potential, was reinforced with a bioabsorbable 3D-printed framework to support physiological loads. Polycaprolactone (PCL) was 3D-printed in two configurations, rectilinear and gyroid designs, that were extensively mechanically characterised. Both scaffold designs increased the compressive modulus of the CHyA matrices by three orders of magnitude, mimicking the physiological range (0.5-2.0 MPa) of healthy cartilage. The gyroid scaffold proved to be more flexible compared to the rectilinear scaffold, thus better contouring to the curvature of a femoral condyle. Additionally, PCL reinforcement of the CHyA matrix increased the tensile modulus and allowed for suture fixation of the scaffold to the subchondral bone, thus addressing the major challenge of biomaterial fixation to articular joint surfaces in shallow defects. In vitro evaluation confirmed successful infiltration of human mesenchymal stromal cells (MSCs) within the PCL-CHyA scaffolds, which resulted in increased production of sulphated glycosaminoglycans (sGAG/DNA; p = 0.0308) compared to non-reinforced CHyA matrices. Histological staining using alcian blue confirmed these results, while also indicating greater spatial distribution of sGAG throughout the PCL-CHyA scaffold. These findings have a great clinical importance as they provide evidence that reinforced PCL-CHyA scaffolds, with their increased chondroinductive potential and compatibility with joint fixation techniques, could be used to repair large-area chondral defects that currently lack effective treatment options.

Spatial correction improves accuracy of catheter positioning during ablation of premature ventricular contractions: differences between ventricular outflow tracts and other localizations.

BACKGROUND: Hybrid activation mapping is a novel tool to correct for spatial displacement of the mapping catheter due to asymmetrical contraction of myocardium during premature ventricular contractions (PVC). The aim of this study is to describe and improve our understanding of spatial displacement during PVC mapping as well as options for correction using hybrid activation mapping. METHODS AND RESULTS: We analyzed 5798 hybrid mapping points in 40 acquired hybrid maps of 22 consecutive patients (age 63 ± 16 years, 45% female) treated for premature ventricular contractions (PVCs). Median PVC-coupling interval was 552 ms (IQR 83 ms). Spatial displacement was determined by measuring the dislocation of the catheter tip during PVC compared to the preceding sinus beat. Mean spatial displacement was 3.8 ± 1.5 mm for all maps. The displacement was 1.3 ± 0.4 mm larger for PVCs with non-outflow-tract origin compared to PVCs originating from the ventricular outflow tracts (RVOT/LVOT; p = 0.045). Demographic parameters, PVC-coupling-interval and chamber of origin had no significant influence on the extent of spatial displacement. CONCLUSION: Ectopic activation of the ventricular myocardium during PVCs results in spatial displacement of mapping points that is significantly larger for PVCs with non-outflow-tract origin. The correction for spatial displacement may improve accuracy of radiofrequency current (RFC)-application in catheter ablation of PVCs.

Monthly mobility inferred from isoscapes and laser ablation strontium isotope ratios in caprine tooth enamel.

Strontium isotopic analysis of sequentially formed tissues, such as tooth enamel, is commonly used to study provenance and mobility of humans and animals. However, the potential of 87Sr/86Sr in tooth enamel to track high-frequency movements has not yet been established, in part due to the lack of data on modern animals of known movement and predictive model of isotope variation across the landscape. To tackle this issue, we measured the 87Sr/86Sr in plant samples taken from a 2000 km2 area in the Altai Mountains (Mongolia), and the 87Sr/86Sr in tooth enamel of domestic caprines whose mobility was monitored using GPS tracking. We show that high-resolution, sequential profiles of strontium isotope composition of tooth enamel reliably reflect the high-frequency mobility of domestic livestock and that short-term residency of about 45 days can be resolved. This offers new perspectives in various disciplines, including forensics, ecology, palaeoanthropology, and bioarchaeology.

Triggered activity in atrial myocytes is influenced by Na+/Ca2+ exchanger activity in genetically altered mice.

AIMS: In atrial fibrillation, increased function of the Na+/Ca2+-exchanger (NCX) is one among several electrical remodeling mechanisms. METHODS/RESULTS: Using the patch-clamp- and Ca2+ imaging-methods, we investigated atrial myocytes from NCX-homozygous-overexpressor (OE)- and heterozygous-knockout (KO)-mice and their corresponding wildtypes (WTOE; WTKO). NCX mediated Ca2+ extrusion capacity was reduced in KO and increased in OE. There was no evidence for structural or molecular remodeling. During a proarrhythmic pacing-protocol, the number of low amplitude delayed afterdepolarizations (DADs) was unaltered in OE vs. WTOE and KO vs. WTKO. However, DADs triggered full spontaneous action potentials (sAP) significantly more often in OE vs. WTOE (ratio sAP/DAD: OE:0.18±0.05; WTOE:0.02±0.02; p<0.001). Using the same protocol, a DAD triggered an sAP by tendency less often in KO vs. WTKO (p=0.06) and significantly less often under a more aggressive proarrhythmic protocol (ratio sAP/DAD: KO:0.01±0.003; WT KO: 0.12±0.05; p=0.007). The DAD amplitude was increased in OE vs. WTOE and decreased in KO vs. WTKO. There were no differences in SR-Ca2+-load, the number of spontaneous Ca2+-release-events or IKACh/IK1. CONCLUSIONS: Atrial myocytes with increased NCX expression exhibited increased vulnerability towards sAPs while atriomyocytes with reduced NCX expression were protected. The underlying mechanism consists of a modification of the DAD-amplitude by the level of NCX-activity. Thus, although the number of spontaneous Ca2+-releases and therefore DADs is unaltered, the higher DAD-amplitude in OE made a transgression of the voltage-threshold of an sAP more likely. These findings indicate that the level of NCX activity could influence triggered activity in atrial myocytes independent of possible remodeling processes.

Implementation of an in-house quantitative real-time polymerase chain reaction method for Hepatitis B virus quantification in West African countries.

Hepatitis B virus (HBV) is a major cause of chronic liver disease worldwide. HBV infection is diagnosed by serological tests, while real-time polymerase chain reaction (qRT-PCR) assays are used to quantify viral load, which is a crucial parameter to determine viral replication and to monitor antiviral treatments. However, measuring viral load in resource-limited countries remains nonsystematic, due to the high cost of commercial kits. Here, we describe the development, validation and implementation of a low-cost, in-house qRT-PCR assay to monitor HBV viral load in chronic carriers enrolled in the PROLIFICA programme in the Gambia and Senegal. Over 1500 HBsAg-positive patients, including 210 chronically infected HBV patients, who were given antiviral treatment (tenofovir), were monitored by qRT-PCR using the SYBR Green- and HBV-specific primers. Twenty-four tenofovir-treated patients were followed up and their viral load was tested every 3 months over the 12-month experimental time course. Compared to commercial assays, our in-house assay was shown to be (i) highly reliable, with good intra- and interassay reproducibility over a wide range (45-4.5 × 108 copies mL-1 ), (ii) very similar in the viral loads detected (R2  = .90), (iii) highly sensitive, as it detected loads as low as 30 copies mL-1 (~5 IU mL-1 ), (iv) cheaper (2- to 3-fold), (v) easier to implement and (vi) more rapid. Based on our experience, we recommend this assay as a reliable alternative to commercial assays, for monitoring HBV viraemia in resource-limited, highly endemic countries to reduce the cost and technical obstacles associated with commercial kits.

The microphysics of collisionless shock waves.

Collisionless shocks, that is shocks mediated by electromagnetic processes, are customary in space physics and in astrophysics. They are to be found in a great variety of objects and environments: magnetospheric and heliospheric shocks, supernova remnants, pulsar winds and their nebulæ, active galactic nuclei, gamma-ray bursts and clusters of galaxies shock waves. Collisionless shock microphysics enters at different stages of shock formation, shock dynamics and particle energization and/or acceleration. It turns out that the shock phenomenon is a multi-scale non-linear problem in time and space. It is complexified by the impact due to high-energy cosmic rays in astrophysical environments. This review adresses the physics of shock formation, shock dynamics and particle acceleration based on a close examination of available multi-wavelength or in situ observations, analytical and numerical developments. A particular emphasis is made on the different instabilities triggered during the shock formation and in association with particle acceleration processes with regards to the properties of the background upstream medium. It appears that among the most important parameters the background magnetic field through the magnetization and its obliquity is the dominant one. The shock velocity that can reach relativistic speeds has also a strong impact over the development of the micro-instabilities and the fate of particle acceleration. Recent developments of laboratory shock experiments has started to bring some new insights in the physics of space plasma and astrophysical shock waves. A special section is dedicated to new laser plasma experiments probing shock physics.

Hepatitis E virus infection and acute-on-chronic liver failure in West Africa: a case-control study from The Gambia.

BACKGROUND: In sub-Saharan Africa, it is unknown whether hepatitis E virus (HEV) infection is a common precipitating event of acute-on-chronic liver failure (ACLF). AIMS: To estimate the prevalence of HEV infection in general population and assess whether HEV is a common trigger of ACLF in cirrhotic patients in The Gambia, West Africa. METHODS: We first conducted an HEV sero-survey in healthy volunteers. We then tested cirrhotic patients with ACLF (cases) and compensated cirrhosis (controls) for anti-HEV IgG as a marker of exposure to HEV, and anti-HEV IgA and HEV RNA as a marker of recent infection. We also described the characteristics and survival of the ACLF cases and controls. RESULTS: In the healthy volunteers (n = 204), 13.7% (95% CI: 9.6-19.2) were positive for anti-HEV IgG, and none had positive HEV viraemia. After adjusting for age and sex, the following were associated with positive anti-HEV IgG: being a Christian, a farmer, drinking water from wells, handling pigs and eating pork. In 40 cases (median age: 45 years, 72.5% male) and 71 controls (39 years, 74.6% male), ≥70% were infected with hepatitis B virus. Although hepatitis B flare and sepsis were important precipitating events of ACLF, none had marker of acute HEV. ACLF cases had high (70.0%) 28-day mortality. CONCLUSIONS: Hepatitis E virus infection is endemic in The Gambia, where both faecal-oral route (contaminated water) and zoonotic transmission (pigs/pork meat) may be important. However, acute HEV was not a common cause of acute-on-chronic liver failure in The Gambia.

Ultrafast Synchrotron-Enhanced Thermalization of Laser-Driven Colliding Pair Plasmas.

We report on the first self-consistent numerical study of the feasibility of laser-driven relativistic pair shocks of prime interest for high-energy astrophysics. Using a QED-particle-in-cell code, we simulate the collective interaction between two counterstreaming electron-positron jets driven from solid foils by short-pulse (~60 fs), high-energy (~100 kJ) lasers. We show that the dissipation caused by self-induced, ultrastrong (>10^{6} T) electromagnetic fluctuations is amplified by intense synchrotron emission, which enhances the magnetic confinement and compression of the colliding jets.

Immune Reconstitution Inflammatory Syndrome Secondary to Mycobacterium kansasii Infection in a Kidney Transplant Recipient.

Nontuberculous mycobacteria (NTM) infection is a challenging diagnosis for clinicians in solid organ transplantation. Immune reconstitution inflammatory syndrome (IRIS) is so far unreported in this context. We report here the case of a renal transplant recipient who developed Mycobacterium kansasii-associated lymphadenitis complicated by IRIS while undergoing reduction of his immunosuppressive therapy. For IRIS, the patient required low-dose steroids and an increase in global immunosuppression, in association with NTM antibiotherapy.

Association between IL28B polymorphism, TNFα and biomarkers of insulin resistance in chronic hepatitis C-related insulin resistance.

TNFα has been shown to play a role in hepatitis C virus (HCV)-induced insulin resistance (IR). Polymorphism of the IL28B gene that encodes IFN-lambda 3 may be associated with IR through modulation of TNFα. The aim of this study was to investigate the relationship between IL28B rs12979860 genotype, the level of TNFα activation and the degree of IR in patients with chronic hepatitis C. One hundred and thirty-three nondiabetic genotype 1 HCV-infected patients with biopsy proven noncirrhotic hepatitis C were investigated for IR (using HOMA index), IL28B rs12979860 genotype and fasting circulating levels of soluble receptor 1 of TNFα (sTNFR1) and adipokines: leptin, adiponectin and IL-6. The HOMA-IR was positively correlated with serum levels of leptin (r = 0.35, P < 0.0001) and sTNFR1 (r = 0.35, P < 0.0001) but not with IL-6 or adiponectin. IL28B rs12979860 CC genotype was observed in 35% patients. Genotype CC and nongenotype CC patients were similar in terms of HOMA-IR (means 1.6 ± 0.9 vs 1.7 ± 1.4) and had similar circulating levels of sTNFR1 and adipokines. Independent factors associated with IR were ferritin (OR = 1.002, P = 0.02), leptin (OR = 1.06, P = 0.02) and sTNFR1 (OR = 7.9, P = 0.04). This study suggests that in nondiabetic, noncirrhotic, HCV genotype 1-infected patients, there is no relationship between IL28B rs12979860 genotype and HOMA-IR or sTNFR1 level. HCV-related IR may be mediated through TNFα independent of IL28B genotype.

Characterization of harbor sediments from the English Channel: assessment of heavy metal enrichment, biological effect and mobility.

For a full assessment of the environmental risk posed by dredged sediments not only the anthropogenic enrichment of contaminants, but also their mobility and biological impact should be considered. This study reports on the enrichment factor (EF), mobility, and Adverse Effect Index (AEI) of metals and metalloids in nine dredged sediments. Significant enrichment of As, Cd, Pb and Zn with respect to background values is detected, and calculated AEI values for these elements suggest that it is possible that a corresponding biological effect may be observed. Correlation coefficients also reveal a link between mobility in HCl and enrichment for Cd, Cr, Ni, Pb and Zn, however As and Cu do not display such a link, possibly suggesting that the source of contamination for these elements is less recent. Mobility and enrichment are two parameters which are often studied separately; however this paper shows that in some cases strong correlations occur.

Contemporary ecotypic divergence during a recent range expansion was facilitated by adaptive introgression.

Although rapid phenotypic evolution during range expansion associated with colonization of contrasting habitats has been documented in several taxa, the evolutionary mechanisms that underlie such phenotypic divergence have less often been investigated. A strong candidate for rapid ecotype formation within an invaded range is the three-spine stickleback in the Lake Geneva region of central Europe. Since its introduction only about 140 years ago, it has undergone a significant expansion of its range and its niche, now forming phenotypically differentiated parapatric ecotypes that occupy either the pelagic zone of the large lake or small inlet streams, respectively. By comparing museum collections from different times with contemporary population samples, we here reconstruct the evolution of parapatric phenotypic divergence through time. Using genetic data from modern samples, we infer the underlying invasion history. We find that parapatric habitat-dependent phenotypic divergence between the lake and stream was already present in the first half of the twentieth century, but the magnitude of differentiation increased through time, particularly in antipredator defence traits. This suggests that divergent selection between the habitats occurred and was stable through much of the time since colonization. Recently, increased phenotypic differentiation in antipredator defence traits likely results from habitat-dependent selection on alleles that arrived through introgression from a distantly related lineage from outside the Lake Geneva region. This illustrates how hybridization can quickly promote phenotypic divergence in a system where adaptation from standing genetic variation was constrained.

[Global functional management of mucopolysaccharidoses]. / Prise en charge globale fonctionnelle des mucopolysaccharidoses.

The management of mucopolysaccharidoses (MPS) requires a multidisciplinary approach and all medical and paramedical specialties may be involved because of the multiorgan nature of the disease. For this reason, patients should ideally be managed in a reference center and their management should be coordinated by an experienced physician who has access to the various specialists through a multi-disciplinary approach. The management is focused on assessments of the numerous features of the disease, study their progression and the effectiveness and pitfalls of specific and non-specific treatments. The main concerns of reeducation and rehabilitation should be to preserve global function through specific goals to be set along with the child and its family. This is a very demanding approach for the patient and family in which education plays a fundamental role in order to ensure optimal management.

Prevention of materno-foetal transmission of hepatitis B in sub-Saharan Africa: the evidence, current practice and future challenges.

Hepatitis B (HBV) infection is highly endemic in sub-Saharan Africa (SSA), where more than 8% of the population remain chronic HBV carriers. SSA has one of the highest HBV-related liver cancer rates in the world (CA Cancer J Clin, 55, 2005, 74) and HBV-related liver cancer is the most common cause of premature death in West Africa (Lancet Oncol, 9, 2008, 683; Hepatology, 39, 2004, 211). As such, HBV represents a significant global threat to health in the African continent. Most SSA countries have elected to vaccinate all children against HBV through the WHO-sponsored Expanded Program of Immunization and the current recommendation from WHO-AFRO is for birth-dose HBV vaccination to prevent maternal/child transmission (MFT) and early horizontal transmission of HBV. However, in Africa, HBV vaccine coverage remains low and HBV birth-dose vaccination has not been implemented. HBV transmission from mother to child in the early perinatal period therefore remains a significant contributor to the burden of HBV-related disease in SSA. This review explores the evidence for materno-foetal transmission of HBV in SSA, outlining current practice for HBV MFT prevention and identifying the significant challenges to implementation of HBV prevention in SSA.

Food intake increases liver stiffness measurements and hampers reliable values in patients with chronic hepatitis B and healthy controls: the PROLIFICA experience in The Gambia.

BACKGROUND: By increasing the hepatic blood circulation, food intake has been suggested to increase liver stiffness measurement (LSM) values in HCV-infected patients. AIM: To investigate prospectively the effects of food intake on LSM in hepatitis B virus (HBV)-infected patients and healthy controls. METHODS: In The Gambia, patients included in the PROLIFICA project are screened for HBV at the community level and then invited for fasting assessment including LSM. Between April 2012 and October 2012, each day, the first five participants were invited to participate in this study. After the initial examination, a standardised 850 Kcal breakfast was provided. Effect of food intake was assessed by examining mean difference of LSM, IQR and IQR/LSM at T0 (fasting LSM1), T30min (LSM2) and T120min (LSM3) respectively. RESULTS: A total of 209 subjects were enrolled in this study (133 were HBV positive, 76 healthy controls). Unreliable measurements occurred more frequently after food intake (5%, 24% and 18% at T0, T30min and T120min respectively). In both groups, median LSM2 was significantly higher than LSM1 [6.2 (IQR: 5.4, 7.9)] vs. 4.9 (4.2, 6.2), P < 0.0001. LSM3 was still higher than the baseline, but lower than LSM2. In multivariable analysis, no factor modified the effect of breakfast on LSM. In a subgroup of patients having liver biopsies, we confirmed that food intake can overestimate liver fibrosis. CONCLUSIONS: Food intake significantly increases liver stiffness measurement and its IQR values in patients with chronic hepatitis B as well as healthy individuals; and also the number of unreliable liver stiffness measurement values.