Molecular Characterization of Strains of Respiratory Syncytial Virus Identified in a Hematopoietic Stem Cell Transplant Outpatient Unit Over 2 Years: Community or Nosocomial Infection?

Respiratory syncytial virus (RSV) is recognized as the leading cause of nosocomial respiratory infection among hematopoietic stem cell transplant (HSCT) recipients, causing considerable morbidity and mortality. RSV is easily transmitted by contact with contaminated surfaces, and in HSCT units, more than 50% of RSV infections have been characterized as of nosocomial origin. From April 2001 to October 2002, RSV was identified by direct immunofluorescent assay in 42 symptomatic HSCT recipients. Seven RSV strains from 2001 and 12 RSV strains from 2002 were sequenced. RNA extraction, cDNA synthesis, and seminested polymerase chain reaction (PCR) with primers complementary to RSV genes G and F were pet-formed. PCR products were analyzed by nucleotide sequencing of the C-terminal region of gene G for typing (in group A or B). Of the 7 strains analyzed in 2001, only 2 belonged to group B; the other 5 belonged to group A. Of these 7 strains, 3 were identical and were from recipients receiving outpatient care. In 2002, of the 12 strains analyzed, 3 belonged to group A and the other 9 belonged to group B. Of these 9 strains, 7 were genetically identical and were also from recipients receiving outpatient care. Therefore, multiple strains of RSV cocirculated in the hematopoietic stem cell transplant units (ward and outpatient units) between 2001 and 2002. Nosocomial transmission was more likely to occur at the HSCT outpatient unit than in the HSCT ward. Infection control practices should also be implemented in the outpatient setting.

Monoclonal B-cell lymphocytosis in first-degree relatives of patients with sporadic (non-familial) chronic lymphocytic leukaemia

Although biological similarities have been described among monoclonal B-cell lymphocytosis (MBL) and chronic lymphocytic leukaemia (CLL), the relationships between these two conditions are not fully understood, and new epidemiological studies in different populations and different countries continue to be reported. Here, we investigated 167 first-degree relatives from 42 families of patients with non-familial (sporadic) CLL, using four-colour flow cytometry. MBL was found in seven of 167 subjects (4.1%). Monoclonality was detected in all cases either by light-chain restriction or by polymerase chain reaction. Fluourescence in situ hybridization did not show any chromosomal abnormality. The prevalence of MBL according to age was 0 (0/54) in individuals aged less than 40 years, 2.5% (2/81) between 40 and 60 years, and 15.6% (5/32) in individuals over 60 years. The prevalence of MBL cases in individuals over 60 years was similar to that found in familial CLL relatives at the same age group. This suggests that in older first-degree relatives of patients with sporadic CLL, the risk of MBL detection is as high as in older first-degree relatives from CLL families, which could render these individuals belonging to `sporadic CLL families` as susceptible as individuals from `familial CLL` to the development of clinical CLL.

TAC3/TACR3 Mutations Reveal Preferential Activation of Gonadotropin-Releasing Hormone Release by Neurokinin B in Neonatal Life Followed by Reversal in Adulthood

Context: Mutations in TAC3 and TACR3 (encoding neurokinin B and its receptor) have been identified in Turkish patients with idiopathic hypogonadotropic hypogonadism (IHH), but broader populations have not yet been tested and genotype-phenotype correlations have not been established. Objective: A broad cohort of normosmic IHH probands was screened for mutations in TAC3/TACR3 to evaluate the prevalence of such mutations and define the genotype/phenotype relationships. Design and Setting: The study consisted of sequencing of TAC3/TACR3, in vitro functional assays, and neuroendocrine phenotyping conducted in tertiary care centers worldwide. Patients or Other Participants: 345 probands, 18 family members, and 292 controls were studied. Intervention: Reproductive phenotypes throughout reproductive life and before and after therapy were examined. Main Outcome Measure: Rare sequence variants in TAC3/TACR3 were detected. Results: In TACR3, 19 probands harbored 13 distinct coding sequence rare nucleotide variants [three nonsense mutations, six nonsynonymous, four synonymous (one predicted to affect splicing)]. In TAC3, one homozygous single base pair deletion was identified, resulting in complete loss of the neurokinin B decapeptide. Phenotypic information was available on 16 males and seven females with coding sequence variants in TACR3/TAC3. Of the 16 males, 15 had microphallus; none of the females had spontaneous thelarche. Seven of the 16 males and five of the seven females were assessed after discontinuation of therapy; six of the seven males and four of the five females demonstrated evidence for reversibility of their hypogonadotropism. Conclusions: Mutations in the neurokinin B pathway are relatively common as causes of hypogonadism. Although the neurokinin B pathway appears essential during early sexual development, its importance in sustaining the integrity of the hypothalamic-pituitary-gonadal axis appears attenuated over time. (J Clin Endocrinol Metab 95: 2857-2867, 2010)

The association of prevalent medial meniscal pathology with cartilage loss in the medial tibiofemoral compartment over a 2-year period

Objective: To investigate the association of different types of magnetic resonance imaging (MRI)-detected medial meniscal pathology with subregional cartilage loss in the medial tibiofemoral compartment. Methods: A total of 152 women aged >= 40 years, with and without knee osteoarthritis (OA) were included in a longitudinal 24-month observational study. Spoiled gradient recalled acquisitions at steady state (SPGR) and T2-weighted fat-suppressed MRI sequences were acquired. Medial meniscal status of the anterior horn (AH), body, and posterior horn (PH) was graded at baseline: 0 (normal), 1 (intrasubstance meniscal signal changes), 2 (single tears), and 3 (complex tears/maceration). Cartilage segmentation was performed at baseline and 24-month follow-up in various tibiofemoral subregions using computation software. Multiple linear regression models were applied for the analysis with cartilage loss as the outcome. In a first model, the results were adjusted for age and body mass index (BMI). In a second model, the results were adjusted for age, BMI and medial meniscal extrusion. Results: After adjusting for age, BMI, and medial meniscal extrusion, cartilage loss in the total medial tibia (MT) (0.04 mm, P=0.04) and the external medial tibia (eMT) (0.068 mm, P=0.04) increased significantly for compartments with grade 3 lesions. Cartilage loss in the total central medial femoral condyle (cMF) (0.071 mm, P=0.03) also increased significantly for compartments with grade 2 lesions. Cartilage loss at the eMT was significantly related to tears of the PH (0.074 mm; P=0.03). Cartilage loss was not significantly increased for compartments with grade 1 lesions. Conclusion: The protective function of the meniscus appears to be preserved in the presence of intrasubstance meniscal signal changes. Prevalent single tears and meniscal maceration were found to be associated with increased cartilage loss in the same compartment, especially at the PH. (C) 2009 Osteoarthritis Research Society International. Published by Elsevier Ltd. All rights reserved.

An assessment of the latent and sensible heat flux on the simulated regional climate over Southwestern South Atlantic Ocean

A Regional Climate Model (RegCM3) 10-year (1990-1999) simulation over southwestern South Atlantic Ocean (SAO) is evaluated to assess the mean climatology and the simulation errors of turbulent fluxes over the sea. Moreover, the relationship between these fluxes and the rainfall over some cyclogenetic areas is also analyzed. The RegCM3 results are validated using some reanalyses datasets (ERA40, R2, GPCP and WHOI). The summer and winter spatial patterns of latent and sensible heat fluxes simulated by the RegCM3 are in agreement with the reanalyses (WHOI, R2 and ERA40). They show large latent heat fluxes exchange in the subtropical SAO and at higher latitudes in the warm waters of Brazil Current. In particular, the magnitude of RegCM3 latent heat fluxes is similar to the WHOI, which is probably related to two factors: (a) small specific humidity bias, and (b) the RegCM3 flux algorithm. In contrast, the RegCM3 presents large overestimation of sensible heat flux, though it simulates well their spatial pattern. This simulation error is associated with the RegCM3 underestimation of the 2-m air temperature. In southwestern SAO, in three known cyclogenetic areas, the reanalyses and the RegCM3 show the existence of different physical mechanisms that control the annual cycles of latent/sensible heating and rainfall. It is shown that over the eastern coast of Uruguay (35A degrees-43A degrees S) and the southeastern coast of Argentina (44A degrees-52A degrees S) the sea-air moisture and heat exchange play an important role to control the annual cycle of precipitation. This does not happen on the south/southeastern coast of Brazil.

Ground-based detection of sprites and their parent lightning flashes over Africa during the 2006 AMMA campaign

Sprites have been detected in video camera observations from Niger over mesoscale convective systems in Nigeria during the 2006 AMMA (African Monsoon Multidisciplinary Analysis) campaign The parent lightning flashes have been detected by multiple Extremely Low Frequency (ELF) receiving stations worldwide The recorded charge moments of the patent lightning flashes are often in excellent agreement between different receiving sites, and are furthermore consistent with conventional dielectric breakdown in the mesosphere as the origin of the sprites Analysis of the polarization of the horizontal magnetic field at the distant receivers provides evidence that the departure from linear magnetic polarization at ELF is caused primarily by the clay night asymmetry of the Earth-ionosphere cavity Copyright (C) 2009 Royal Meteorological Society

Gravimetric study of a potential mineral deposit in the Itapororoca region, Brazil

A semi-detailed gravity survey was carried out over an area of 650 km(2) localized in the Eo-Neoproterozoic coastal zone of Paraiba State where 548 new gravity stations were added to the existing database. Gravity measurements were made with a LaCoste and Romberg model G meter with a precision of 0.04 mGal. The altitude was determined by barometric levelling with a fixed base achieving a 1.2 m measure of uncertainty, corresponding to an overall accuracy of 0.24 mGal for the Bouguer anomaly. The residual Bouguer map for a 7th degree regional polynomial showed a circumscribed negative anomaly coincident with a localized aero-magnetic anomaly and with hydro-thermally altered outcrops, near the city of Itapororoca. The 3D gravity modelling, constrained by geologic mapping was interpreted as a low density, fractured and/or altered material with a most probable volume of approximately 23 km(3), extending to about 8,500 m depth. This result is in accordance with a volcanic body associated with hydrothermal processes accompanied by surface mineralization evidence, which may be of interest to the mining industry.

Differential kinase requirement for enhancement of Fc gamma R-mediated phagocytosis in alveolar macrophages by leukotriene B(4) vs. D(4)

In alveolar macrophages, leukotriene (IT) B(4) and cysteinyl LTs (LTC(4), LTD(4) and LTE(4)) both enhance Fc gamma receptor (Fc gamma R)-mediated phagocytosis. In the present study we investigated the role of specific PKC isoforms (PKC-alpha and -delta), the MAP kinases p38 and ERK 1/2, and PI3K in mediating the potentiation of Fc gamma R-mediated phagocytosis induced by addition of leukotrienes to the AMs. It was found that exogenously added LTB(4) and LTD(4) both enhanced PKC-delta and -alpha phosphorylation during Fc gamma R engagement. Studies with isoform-selective inhibitors indicated that exogenous LTB(4) effects were dependent on both PKC-alpha and -delta, while LTD(4) effects were exclusively due to PKC-delta activation. Although both exogenous LTB(4) and LTD(4) enhanced p38 and ERK 1/2 activation, LTB(4) required only ERK 1/2, while LTD(4) required only p38 activation. Activation by both LTs was dependent on PI3K activation. Effects of endogenous LTs on kinase activation were also investigated using selective LT receptor antagonists. Endogenous LTB(4) contributed to Fc gamma R-mediated activation of PKC-alpha, ERK 1/2 and PI3K, while endogenous cysLTs contributes to activation of PKC-delta, p38 and PI3K. Taken together, our data show that the capacities of LTB(4) and LTD(4) to enhance Fc gamma R-mediated phagocytosis reflect their differential activation of specific kinase programs. (C) 2008 Elsevier Ltd. All rights reserved.

Gradual Decline in Malaria-Specific Memory T Cell Responses Leads to Failure to Maintain Long-Term Protective Immunity to Plasmodium chabaudi AS Despite Persistence of B Cell Memory and Circulating Antibody

The mechanisms responsible for the generation and maintenance of immunological memory to Plasmodium are poorly understood and the reasons why protective immunity in humans is so difficult to achieve and rapidly lost remain a matter for debate. A possible explanation for the difficulty in building up an efficient immune response against this parasite is the massive T cell apoptosis resulting from exposure to high-dose parasite Ag. To determine the immunological mechanisms required for long-term protection against P. chabaudi malaria and the consequences of high and low acute phase parasite loads for acquisition of protective immunity, we performed a detailed analysis of T and B cell compartments over a period of 200 days following untreated and drug-treated infections in female C57BL/6 mice. By comparing several immunological parameters with the capacity to control a secondary parasite challenge, we concluded that loss of full protective immunity is not determined by acute phase parasite load nor by serum levels of specific IgG2a and IgG1. Abs, but appears to be a consequence of the progressive decline in memory T cell response to parasites, which occurs similarly in untreated and drug-treated mice with time after infection. Furthermore, by analyzing adoptive transfer experiments, we confirmed the major role of CD4(+) T cells for guaranteeing long-term full protection against P. chabaudi malaria. The Journal of Immunology, 2008, 181: 8344-8355.

In vitro sensitivity of Leishmania (Viannia) braziliensis and Leishmania (Leishmania) amazonensis Brazilian isolates to meglumine antimoniate and amphotericin B

Resistance of Leishmania parasites to specific chemotherapy has become a well-documented problem in the Indian subcontinent in recent years but only a few studies have focused on the susceptibility of American Leishmania isolates. Our susceptibility assays to meglumine antimoniate were performed against intracellular amastigotes after standardizing an in vitro model of macrophage infection appropriate for Leishmania (Viannia) braziliensis isolates. For the determination of promastigote susceptibility to amphotericin B, we developed a simplified MTT-test. The sensitivity in vitro to meglumine antimoniate and amphotericin B of 13 isolates obtained from Brazilian patients was determined. L. (V.) braziliensis isolates were more susceptible to meglumine antimoniate than Leishmania (Leishmania) amazonensis. EC(50), EC(90) and activity indexes (calculated over the sensitivity of reference strains), suggested that all isolates tested were susceptible in vitro to meglumine antimoniate, and did not show association with the clinical outcomes. Isolates were also uniformly susceptible in vitro to amphotericin B.

The analytic torsion of a cone over an odd dimensional manifold

We study the analytic torsion of a cone over an orientable odd dimensional compact connected Riemannian manifold W. We prove that the logarithm of the analytic torsion of the cone decomposes as the sum of the logarithm of the root of the analytic torsion of the boundary of the cone, plus a topological term, plus a further term that is a rational linear combination of local Riemannian invariants of the boundary. We show that this last term coincides with the anomaly boundary term appearing in the Cheeger Muller theorem [3, 2] for a manifold with boundary, according to Bruning and Ma (2006) [5]. We also prove Poincare duality for the analytic torsion of a cone. (C) 2010 Elsevier B.V. All rights reserved.

Homotopy type of gauge groups of quaternionic line bundles over spheres

Let P be a principal S(3)-bundle over a sphere S(n), with n >= 4. Let G(p) be the gauge group of P. The homotopy type of G(p) when n - 4 was studied by A. Kono in [A. Kono, A note on the homotopy type of certain gauge groups, Proc. Roy. Soc. Edinburgh Sect. A 117 (1991) 295-297]. In this paper we extend his result anti we study the homotopy type of the gauge group of these bundles for all n <= 25. (C) 2008 Elsevier B.V. All rights reserved.

Numerical study of the atmospheric flow over a coastal cliff

This work presents a numerical method suitable for the study of the development of internal boundary layers (IBL) and their characteristics for flows over various types of coastal cliffs. The IBL is an important meteorological occurrence for flows with surface roughness and topographical step changes. A two-dimensional flow program was used for this study. The governing equations were written using the vorticity-velocity formulation. The spatial derivatives were discretized by high-order compact finite differences schemes. The time integration was performed with a low storage fourth-order Runge-Kutta scheme. The coastal cliff (step) was specified through an immersed boundary method. The validation of the code was done by comparison of the results with experimental and observational data. The numerical simulations were carried out for different coastal cliff heights and inclinations. The results show that the predominant factors for the height of the IBL and its characteristics are the upstream velocity, and the height and form (inclination) of the coastal cliff. Copyright (C) 2010 John Wiley & Sons, Ltd.

QCD sum rules for the production of the X(3872) as a mixed molecule-charmonium state in B meson decay

We use QCD sum rules to calculate the branching ratio for the production of the meson X(3872) in the decay B -> X(3872)K, assumed to be a mixture between charmonium and exotic molecular vertical bar c (q) over bar vertical bar vertical bar q (c) over bar vertical bar states with J(PC) = 1(++). We find that in a small range for the values of the mixing angle, 5 degrees <= theta <= 13 degrees, we get the branching ratio B(B -> XK) = (1.00 +/- 0.68) x 10(-5), which is in agreement with the experimental upper limit. This result is compatible with the analysis of the mass and decay width of the mode J/psi(n pi) and the radiative decay mode J/psi gamma performed in the same approach. (C) 2011 Elsevier B.V. All rights reserved.

Can the pi(+) chi(c1) resonance structures be D*(D)over-bar* and D(1)(D)over-bar molecules?

We use QCD sum rules to study the recently observed resonance-like structures in the pi(+)chi(c1) mass distribution, Z(1)(+) (4050) and Z(2)(+) (4250), considered as D*(+) (D) over bar*(0) and D(1)(+) (D) over bar (0) + D(+) (D) over bar (0)(1) molecules with the quantum number J(P) = 0(+) and J(P) = 1-, respectively. We consider the contributions of condensates up to dimension eight and work at leading order in alpha(s). We obtain m(D*D*) = (4.15 +/- 0.12) GeV, around 100 MeV above the D*D* threshold, and m(D1D) = (4.19 +/- 0.22) GeV, around 100 MeV below the D(1)D threshold. We conclude that the D*(+)(D) over bar*(0) state is probably a virtual state that is not related with the Z(1)(+) (4050) resonance-like structure. In the case of the D(1)D molecular state, considering the errors, its mass is consistent with both Z(1)(+)(4050) and Z(2)(+)(4250) resonance-like structures. Therefore, we conclude that no definite conclusion can be drawn for this state from the present analysis. (C) 2008 Elsevier B.V All rights reserved.