Avaliação da depleção linfóide folicular da Bursa de Fabricius: uma metodologia alternativa utilizando análise digital de imagem e redes neurais artificiais

Fifty Bursa of Fabricius (BF) were examined by conventional optical microscopy and digital images were acquired and processed using Matlab® 6.5 software. The Artificial Neuronal Network (ANN) was generated using Neuroshell® Classifier software and the optical and digital data were compared. The ANN was able to make a comparable classification of digital and optical scores. The use of ANN was able to classify correctly the majority of the follicles, reaching sensibility and specificity of 89% and 96%, respectively. When the follicles were scored and grouped in a binary fashion the sensibility increased to 90% and obtained the maximum value for the specificity of 92%. These results demonstrate that the use of digital image analysis and ANN is a useful tool for the pathological classification of the BF lymphoid depletion. In addition it provides objective results that allow measuring the dimension of the error in the diagnosis and classification therefore making comparison between databases feasible.Cinquenta Bursa de Fabrícius (BF) foram examinadas através de microscopia óptica convencional e imagens digitais foram obtidas e processadas através do software Matlab® 6.5. Redes Neurais Artificiais (ANN) foram geradas com a utilização do software Neuroshell® Classifier, e os dados das análises óptica e digital foram comparados. A ANN classificou corretamente a maioria dos folículos, atingindo sensibilidade e especificidade de 89% e 96%, respectivamente. Quando os folículos foram agrupados de forma binária houve um aumento da sensibilidade para 90% e obteve-se um valor máximo para a especificidade de 92%. Estes resultados demonstram que o uso da análise digital de imagem associada à ANNé uma ferramenta bastante útil para a classificação patológica da depleção linfóide da BF. Além disso, fornece resultados objetivos que permitem medir a dimensão do erro classificatório, tornando possível a comparação entre distintos bancos de dados

An Assessment of Risk of Iodine Deficiency Among Pregnant Women in Sarawak, Malaysia

Previous findings from a state-wide Iodine Deficiency Disorders (IDD) study among pregnant women (PW) in Sarawak indicated that PW are at risk of IDD and further assessment is needed. This paper describes the methodology used in conducting this study for an assessment of risk of iodine deficiency among pregnant women in Sarawak, Malaysia. A total of 30 maternal child health care clinics (MCHCs) were selected using probability proportional to population size (PPS) sampling technique. The PW sample size was calculated based on 95% confidence interval (CI), relative precision of 5%, design effect of 2, anticipated IDD prevalence of 65.0% and non-response rate of 20%. Thus, the total sample size required was 750 (25 respondents per selected MCHC). The WHO Expanded Programme on Immunization (EPI) surveys approach was used to randomly select the first respondent and subsequent respondents were chosen until the required number of PW was met. The required data were obtained through: face-to-face interviews (socio-demographic and food frequency questionnaire), clinical assessments (thyroid size, and hyper/hypothyroidism) and biochemical analysis (urine and blood serum). A total of 677 PW responded in the study with a response rate of 90.2%. Majority of the PW were at second gravida, aged 25-29 years old and of Malay ethnicity. The methodology used in this study was based on International guidelines which may provide state's estimates. All the necessary steps were taken into consideration to ensure valid and reliable findings on current iodine status among PW

Platelet FcγRIIA-induced serotonin release exacerbates the severity of Transfusion-Related Acute Lung Injury in mice

Transfusion-related acute lung injury (TRALI) remains a major cause of transfusion-related fatalities. The mechanism of human antibody-mediated TRALI, especially the involvement of the Fcγ receptors, is not clearly established. Contrary to mice, human platelets are unique in their expression of the FcγRIIA/CD32A receptor, suggesting that our understanding of the pathogenesis of antibody-mediated TRALI is partial, as the current murine models incompletely recapitulate the human immunology. We evaluated the role of FcγRIIA/CD32A in TRALI using a humanized mouse model expressing the FcγRIIA/CD32A receptor. When challenged with a recombinant chimeric human immunoglobulin G1/mouse anti–major histocompatibility complex class I monoclonal antibody, these mice exhibited exacerbated alveolar edema and higher mortality compared with wild-type (WT) mice. Unlike in WT mice, monocytes/macrophages in CD32A(+) mice were accessory for TRALI initiation, indicating the decisive contribution of another cell type. Platelet activation was dramatically increased in CD32A(+) animals, resulting in their increased consumption and massive release of their granule contents. Platelet depletion prevented the exacerbation of TRALI in CD32A(+) mice but did not affect TRALI in WT animals. By blocking platelet serotonin uptake with fluoxetine, we showed that the severity of TRALI in CD32A(+) mice resulted from the serotonin released by the activated platelets. Furthermore, inhibition of 5-hydroxytryptamine 2A serotonin receptor with sarpogrelate, before or after the induction of TRALI, abolished the aggravation of lung edema in CD32A(+) mice. Our findings show that platelet FcγRIIA/CD32A activation exacerbates antibody-mediated TRALI and provide a rationale for designing prophylactic and therapeutic strategies targeting the serotonin pathway to attenuate TRALI in patients

Darboux Transformations, Infinitesimal Symmetries and Conservation Laws for Nonlocal Two-Dimensional Toda Lattice

The technique of Darboux transformation is applied to nonlocal partner of two-dimensional periodic A_{n-1} Toda lattice. This system is shown to admit a representation as the compatibility conditions of direct and dual overdetermined linear systems with quantized spectral parameter. The generalization of the Darboux transformation technique on linear equations of such a kind is given. The connections between the solutions of overdetermined linear systems and their expansions in series at singular points neighborhood are presented. The solutions of the nonlocal Toda lattice and infinite hierarchies of the infinitesimal symmetries and conservation laws are obtained.Comment: 12 pages, infinitesimal symmetries and conservation laws are adde

The ATP-gated P2X1 ion channel contributes to the severity of antibody-mediated Transfusion-Related Acute Lung Injury in mice

The biological responses that control the development of Transfusion-Related Acute Lung Injury (TRALI), a serious post-transfusion respiratory syndrome, still need to be clarified. Since extracellular nucleotides and their P2 receptors participate in inflammatory processes as well as in cellular responses to stress, we investigated the role of the ATP-gated P2X1 cation channel in antibody-mediated TRALI. The effects of NF449, a selective P2X1 receptor (P2RX1) antagonist, were analyzed in a mouse two-hit model of TRALI. Mice were primed with lipopolysaccharide (LPS) and 24 h later challenged by administrating an anti-MHC I antibody. The selective P2RX1 antagonist NF449 was administrated before the administration of LPS and/or the anti-MHC I antibody. When given before antibody administration, NF449 improved survival while maximal protection was achieved when NF449 was also administrated before the sensitization step. Under this later condition, protein contents in bronchoalveolar lavages were dramatically reduced. Cell depletion experiments indicated that monocytes/macrophages, but not neutrophils, contribute to this effect. In addition, the reduced lung periarteriolar interstitial edemas in NF449-treated mice suggested that P2RX1 from arteriolar smooth muscle cells could represent a target of NF449. Accordingly, inhibition of TRPC6, another cation channel expressed by smooth muscle cells, also reduced TRALI-associated pulmonary interstitial and alveolar edemas. These data strongly suggest that cation channels like P2RX1 or TRPC6 participate to TRALI pathological responses

Formation of topological defects in gauge field theories

When a symmetry gets spontaneously broken in a phase transition, topological defects are typically formed. The theoretical picture of how this happens in a breakdown of a global symmetry, the Kibble-Zurek mechanism, is well established and has been tested in various condensed matter experiments. However, from the viewpoint of particle physics and cosmology, gauge field theories are more relevant than global theories. In recent years, there have been significant advances in the theory of defect formation in gauge field theories, which make precise predictions possible, and in experimental techniques that can be used to test these predictions in superconductor experiments. This opens up the possibility of carrying out relatively simple and controlled experiments, in which the non-equilibrium phase transition dynamics of gauge field theories can be studied. This will have a significant impact on our understanding of phase transitions in the early universe and in heavy ion collider experiments. In this paper, I review the current status of the theory and the experiments in which it can be tested.Comment: Review article, 43 pages, 7 figures. Minor changes, some references added. Final version to appear in IJMP

Nonequilibrium Evolution of Correlation Functions: A Canonical Approach

We study nonequilibrium evolution in a self-interacting quantum field theory invariant under space translation only by using a canonical approach based on the recently developed Liouville-von Neumann formalism. The method is first used to obtain the correlation functions both in and beyond the Hartree approximation, for the quantum mechanical analog of the $\phi^{4}$ model. The technique involves representing the Hamiltonian in a Fock basis of annihilation and creation operators. By separating it into a solvable Gaussian part involving quadratic terms and a perturbation of quartic terms, it is possible to find the improved vacuum state to any desired order. The correlation functions for the field theory are then investigated in the Hartree approximation and those beyond the Hartree approximation are obtained by finding the improved vacuum state corrected up to ${\cal O}(\lambda^2)$. These correlation functions take into account next-to-leading and next-to-next-to-leading order effects in the coupling constant. We also use the Heisenberg formalism to obtain the time evolution equations for the equal-time, connected correlation functions beyond the leading order. These equations are derived by including the connected 4-point functions in the hierarchy. The resulting coupled set of equations form a part of infinite hierarchy of coupled equations relating the various connected n-point functions. The connection with other approaches based on the path integral formalism is established and the physical implications of the set of equations are discussed with particular emphasis on thermalization.Comment: Revtex, 32 pages; substantial new material dealing with non-equilibrium evolution beyond Hartree approx. based on the LvN formalism, has been adde

Quantum dynamics and thermalization for out-of-equilibrium phi^4-theory

The quantum time evolution of \phi^4-field theory for a spatially homogeneous system in 2+1 space-time dimensions is investigated numerically for out-of-equilibrium initial conditions on the basis of the Kadanoff-Baym equations including the tadpole and sunset self-energies. Whereas the tadpole self-energy yields a dynamical mass, the sunset self-energy is responsible for dissipation and an equilibration of the system. In particular we address the dynamics of the spectral (`off-shell') distributions of the excited quantum modes and the different phases in the approach to equilibrium described by Kubo-Martin-Schwinger relations for thermal equilibrium states. The investigation explicitly demonstrates that the only translation invariant solutions representing the stationary fixed points of the coupled equation of motions are those of full thermal equilibrium. They agree with those extracted from the time integration of the Kadanoff-Baym equations in the long time limit. Furthermore, a detailed comparison of the full quantum dynamics to more approximate and simple schemes like that of a standard kinetic (on-shell) Boltzmann equation is performed. Our analysis shows that the consistent inclusion of the dynamical spectral function has a significant impact on relaxation phenomena. The different time scales, that are involved in the dynamical quantum evolution towards a complete thermalized state, are discussed in detail. We find that far off-shell 1 3 processes are responsible for chemical equilibration, which is missed in the Boltzmann limit. Finally, we address briefly the case of (bare) massless fields. For sufficiently large couplings $\lambda$ we observe the onset of Bose condensation, where our scheme within symmetric \phi^4-theory breaks down.Comment: 77 pages, 26 figure

Repeated ovarian stimulation with corifollitropin alfa in patients in a GnRH antagonist protocol: no concern for immunogenicity

BACKGROUND One injection of corifollitropin alfa replaces the first seven daily FSH injections in controlled ovarian stimulation (COS) cycles. Repeated treatment with therapeutic proteins may cause immune responses or hypersensitivity reactions. We assessed the immunogenicity and safety of corifollitropin alfa treatment in up to three COS cycles. METHODS In this multicentre, phase III uncontrolled trial, patients (>60 kg) started treatment with one injection of 150 µg corifollitropin alfa on cycle Day 2 or 3 of menses and 0.25 mg ganielix on stimulation Day 5 or 6. Primary outcome measures were antibody formation against corifollitropin alfa (using highly sensitive radioimmunoprecipitation assay), hypersensitivity reactions, local tolerance and adverse events (AEs). RESULTS First, second and third COS cycles were started by 682, 375 and 198 patients, respectively. No clinically relevant immunogenicity or drug-related hypersensitivity was observed. For 192 patients undergoing their third cycle a post-treatment blood sample was negative in the anti-corifollitropin antibody assay, resulting in an upper limit of the one-sided 95% confidence interval (CI) of 1.5%. Most frequent AEs were procedural pain (17.7%, 95% CI: 14.9–20.8%), headache (9.1%, 95% CI: 7.0–11.5%) and pelvic pain (7.6%, 95% CI: 5.7–9.9%). Cumulative ongoing pregnancy rate after three cycles, including frozen-thawed embryo transfer cycles and spontaneous pregnancies, was 61% (95% CI: 56–65%) after censoring for patients who discontinued. CONCLUSIONS Treatment with corifollitropin alfa can safely and effectively initiate and sustain ovarian stimulation during the first 7 days of COS in normal responder patients undergoing up to three treatment cycles, without concerns of immunogenicity.Robert J. Norman, Fernando Zegers-Hochschild, Bruno S. Salle, Jolanda Elbers, Esther Heijnen, Maya Marintcheva-Petrova, and Bernadette Mannaerts for the Trust Investigator