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The effect of exposure to high temperature on rock strength is a topic of interest in many engineering fields. In general, rock strength is known to decrease as temperature increases. The most common test used to evaluate the rock strength is the uniaxial compressive strength test (UCS). It can only be carried out in laboratory and presents some limitations in terms of the number, type and preparation of the samples. Such constrains are more evident in case of rocks from historical monuments affected by a fire, where the availability of samples is limited. There are alternatives for an indirect determination of UCS, such as the point load test (PLT), or non-destructive tests such as the Schmidt's hammer, that can also be performed in situ. The aims of this research are: (i) measuring the effect of high temperatures and cooling methods on the strength and hardness of a limestone named Pedra de Borriol widely used in several historic buildings on the E of Spain, and (ii) studying the possibility of indirectly obtaining UCS by means of PLT and Leeb hardness tests (LHT), using Equotip type D. Limestone samples were heated to 105 (standard conditions), 200, 300, 400, 500, 600, 700, 800 and 900 ºC and cooled slowly (in air) and quickly (immersed in water). After that, UCS, PLT and LHT tests were performed to evaluate the changes as temperature increases. Results show decreases over 90% in UCS, of between 50 and 70% in PLT index and smaller than 60% in LHT index. Insignificant differences between cooling methods were observed, although slowly cooled samples provide slightly higher values than quickly cooled ones. The results indicate that LHT can be used to indirectly estimate UCS, providing an acceptable prediction. Research on correlating strength parameters in rocks after thermally treated is still scarce. This research novelty provides correlations to predict UCS in historic buildings if affected by a fire, from PLT and non-destructive methods such as LHT whose determination is quicker and easier. [ABSTRACT FROM AUTHOR]

This study investigates which forebrain structures show Fos protein expression during conditioned taste aversion (CTA) acquisition and whether Fos expression depends on the aversion strength. A novel taste paired with an intraperitoneal injection of a low dose of the malaise-inducing agent lithium chloride (LiCl) induced a weak CTA, whereas associating this novel taste with a high dose of LiCl induced a strong CTA. Increasing the strength of the gastric malaise alone enhanced Fos expression in central, basal, and lateral amygdala nuclei and decreased Fos expression in the nucleus accumbens core. Taste--malaise association induced specific Fos activation in the insular cortex (with both the low and the high doses of LiCl) and the nucleus accumbens shell (with the high LiCl dose only). No significant variation of Fos expression was measured in the perirhinal cortex. Several forebrain areas may be sites of taste--malaise convergence during CTA acquisition depending on the strength of the aversion. [ABSTRACT FROM AUTHOR]

Recent studies have shown that the integrity of the entorhinal cortex (EC) is not required for simple contextual conditioning. In background contextual conditioning, i.e., when a phasic cue is present during training, the involvement of the EC is still a matter of debate. Therefore, the present work further examines whether the EC is required for background contextual conditioning using a tone as the phasic cue. Rats sustaining either excitotoxic lesions of the EC or sham-lesions were trained with one of two procedures differing with respect to the predictive value of the tone: a paired procedure in which the tone perfectly predicts shock occurrence and overshadows context, and an unpaired procedure in which the predictive value of the tone is reduced. Conditioned fear was assessed by freezing responses during conditioning, reexposure to the training context, and reexposure to the tone in a new context. Postshock freezing was reduced in rats with entorhinal lesions. In all rats trained with the paired procedure, freezing to the context was low and freezing to the tone was high, suggesting that the tone has overshadowed the context during the conditioning session. The reverse pattern was observed with the unpaired procedure in sham-operated rats. In rats with entorhinal lesions trained with the unpaired procedure, freezing responses to the context was markedly reduced. In a new context, however, entorhinal-lesioned rats showed higher freezing scores than those of sham-lesioned rats. Freezing to the tone was unaffected by the lesion irrespective of the tone's predictive value. As a whole, these results support the notion that the EC is required for normal background contextual freezing. © 2005 Wiley-Liss, Inc. [ABSTRACT FROM AUTHOR]

Recent reports have described reduced populations of CD27+ memory B cells and increased percentages of undifferentiated B cells in peripheral blood of patients with common variable immunodeficiency (CVID). This work has prompted two attempts to classify CVID based on rapid flow cytometric quantification of peripheral blood memory B cells and immature B cells. Evidence to support the hypothesis that suchin vitroB cell classification systems correlate with clinical subtypes of CVID is being sought. For the classification to be useful in routine diagnosis, it is important that the flow cytometric method can be used without prior separation of peripheral blood mononuclear cells (PBMC). We have examined 23 CVID patients and 24 controls, using both PBMC and whole blood, and find an excellent correlation between these methods. The reproducibility of the method was excellent. We classified the CVID patients by all three of the existing classifications, including secretion of immunoglobulin by B cellsin vitroas described by Bryant, as well as the more recent flow cytometric classification methods. Only one patient changed classification as a result of using whole blood. [ABSTRACT FROM AUTHOR]

Background: In coeliac disease (CD) patients, the dominant DQ2-A-I-gliadin peptide recognized by CD4 T cells is contained within peptide sequence 57-73 (p57-73) of A-gliadin. This peptide sequence is also located within a 33-mer protease resistant gliadin fragment and therefore is likely to play an important role in the pathogenesis of CD. Aims: Our aim was to determine whether a B cell epitope was present within the immunodominant T cell epitope of A-gliadin and, if so, to elucidate its sequence and determine the importance of deamidation and/or modification of the amino acid at position 65 for IgA binding. Patients and Methods: A cohort of CD patients, disease controls, and healthy individuals were examined. Serum IgA antibodies to the native and modified p57-73 fragment of A-gliadin were analyzed using enzyme linked immunosorbent assays. Peptide scanning experiments were further used to elucidate the B cell epitope. Results and Conclusion: IgA antibodies to p57-73 were found in 29/72 (40.2%) endomysial antibody positive patients, all of whom had CD. The peptide antibody appeared to be present when patients were on a diet containing gluten and declined on a gluten free diet. The p57-73 antibody was very specific for CD (98%) and had a sensitivity of 56%. The amino acid at position 65 was not important for IgA binding but was crucial for T cell recognition of p57-73. Pentapeptide PXPQP emerges as a potentially strong candidate for the IgA binding motif in this region of A-gliadin. This study shows that a significant proportion of newly diagnosed CD patients have an antibody response to the immunodominant T cell epitope. [ABSTRACT FROM AUTHOR]

We have developed a solid-phase enzyme-linked immunosorbent assay (ELISA) to study the vaccination responses to Vi capsular polysaccharide of Salmonella typhi ( S. typhi Vi) vaccine. Purified S. typhi Vi polysaccharide was biotinylated and bound to streptavidin coated microtitre plates. Reproducibility was determined across a range of IgG antibody levels: mean interassay coefficients of variation (CVs) were <11·9% for non-vaccinated sera with low levels and <11·1% for sera with very high levels of anti- S. typhi Vi IgG. Specificity was assessed by inhibition studies using salmonella antigen. We have developed the ELISA based on normal adult serum responses to test immunization with S. typhi Vi vaccine. We also report here anti- S. typhi Vi IgG levels in a group of healthy preschool children. In non-vaccinated adult sera ( n = 104), the median value of anti -S. typhi Vi IgG, expressed in S. typhi Vi arbitrary units (AU/ml), was 5·3 AU/ml and in non-vaccinated sera from children ( n = 44) the median value was 1·4 AU/ml. The data from immunization of healthy volunteers ( n = 23) show that geometric mean levels of anti- S. typhi Vi IgG were significantly higher ( P < 0·0001) for post-vaccination subjects (39·2 AU/ml) compared to paired prevaccination (3·9 AU/ml) values. A total of 21/23 vaccine recipients had <8 AU/ml S. typhi Vi IgG in their sera prior to vaccination and of these 20/21 (95%) exhibited threefold increases and 14/21 (67%) fourfold increases in their S. typhi Vi IgG following vaccination. Based on the data in this study, we propose a threefold increase in anti- S. typhi Vi IgG post-vaccination to be considered a positive vaccination response. The ability to demonstrate clearly an antibody rise in response to immunization with S. typhi Vi capsular polysaccharide vaccine suggests that this is likely to be a useful vaccine for the assessment of B cell function in patients with suspected immune deficiency. [ABSTRACT FROM AUTHOR]

Summary Common variable immunodeficiency (CVID) is the name given to a clinically heterogeneous group of hypogammaglobulinaemic immunodeficiency states. Bronchiectasis is a feature of this disease and is believed to be the result of recurrent bacterial infection affecting the respiratory tract. Bronchiectasis is also a feature associated with emphysematous changes of the lung in alpha-1 antitrypsin (AAT) deficiency, a serious and relatively common disease, affecting 1 : 2000 in the United Kingdom. This has been demonstrated to result from possession of deficiency alleles, the most clinically important alleles being PI*Z and PI*S. Isolated reports of families with antibody deficiency and AAT deficiency have been published but to date no study has been performed to specifically investigate if AAT deficiency is associated with the lung damage seen in CVID patients. We have developed a PCR genotyping assay that identifies S and Z deficiency alleles and we have used this assay in a preliminary study to investigate the occurrence of these deficiency alleles of AAT in 43 CVID patients. Results of this preliminary study suggest that CVID patients did not have an altered distribution of AAT genes when compared to 70 normal controls. Subgrouping of CVID patients into those with and without bronchiectasis demonstrated a Z allele frequency of 0·077 in those patients with bronchiectasis, which is higher than found in normal controls, namely 0·029 (P < 0·15). Due to the relatively small numbers studied, these results are inconclusive in determining whether AAT deficiency may exacerbate lung damage in some CVID patient, the data does however, indicate that a larger multi-centre study involving many more CVID patients may be useful. [ABSTRACT FROM AUTHOR]

Previous work from this laboratory indicated that methylcholanthrene-induced sarcomas in the rat are infiltrated by cells with the cytotoxic properties of natural killer (NK) cells. Using a combination of velocity sedimentation and analysis and separation in the fluorescence-activated cell sorter, it has been possible to isolate and characterize these putative NK cells. The present results confirm that cytotoxicity is restricted to NK-sensitive targets (syngeneic, allogeneic and xenogeneic) and no evidence was found for cytotoxic T lymphocytes (CTL). In addition, effector cells have the morphology of large granular lymphocytes, and the pattern of expression of five monoclonal antibody-defined surface markers is identical with that of normal splenic NK cells. [ABSTRACT FROM AUTHOR]

In recent years, the importance of characterizing the role of cytokines in a wide range of clinical conditions has resulted in development of new methods to assess cytokine expression in clinical samples. The use of anti-cytokine MoAbs and flow cytometry to detect cytokines intracellularly at the single-cell level has the potential to quantify cytokine production in different diseases. For this technique to be useful in a clinical setting, rapid throughput of clinical samples and a cheap, reliable assay would be required, therefore the development of the above technique using unseparated whole blood samples would be advantageous. Using this technique, only one study to date (Maino et al., 1996) has used unseparated whole blood as the source of cells for detecting intracellular cytokines. In clinical practice, whole blood may be optimal, since this most closely approximates conditions in vivo: as no purification of blood mononuclear cells is required, very little blood is needed to detect a number of cytokines simultaneously in various lymphocyte subpopulations, and the assay can be applied to samples from infants and children. In this study we describe an intracellular cytokine assay using unseparated whole blood from normals. In activated CD8- T cells, IL-2 and interferon-gamma (IFN-γ) were optimally induced after 10h stimulation with phorbol 12-myristate acetate (PMA)/ionomycin, and in CD8+ T cells IL-2 was optimally induced alter 10 h and IFN-γ after 6 h. The levels of IL-2 and IFN-γ in CD8+ and CD8+ T cells in four healthy individuals were consistent on four occasions over a 3-month period. In a large group of 34 normal subjects, there was considerable heterogeneity in CD3/IL-2+ (range 9.7-41.3) and CD3/IFN-γ+ cells (10.1-44), expressed as a percentage of total lymphocytes. In patients with atopic dermatitis (n = 5) there was a significantly decreased percentage of CD3+/CD8+ peripheral blood T cells expressing IFN-γ and an increased percentage of CD3+/CD8+ T cells expressing IL-4 compared with non-atopic dermatitis controls (n = 5). Possible applications of this technique are discussed. [ABSTRACT FROM AUTHOR]

The aim of this work was to carry out an experimental campaign to study the size effect on fretting fatigue. Tests were carried out on a two vertical-actuators fretting-fatigue rig at the University of Brasilia. The study of the size effect was divided into two parts. First, the influence on fretting fatigue life of the volume of material stressed under the contact was investigated. For so, the thickness of the specimens were reduced while maintaining the variation of a multiaxial fatigue parameter with the distance from the surface and the damaged area within the slip zones constant. In addition, the influence of the damaged area within the slip zones was also investigated by reducing it while maintaining all other experimental parameters constant, i.e. bulk fatigue load and tangential load per unit length. These two experimental campaigns were designed and analyzed by applying a multiaxial fatigue criterion in conjunction with the Theory of the Critical Distances (TCD). It was found that none of these two parameters seems to have a significant influence on the fretting fatigue resistance for the Ti–6Al–4V alloy here investigated. • Experimental fretting fatigue campaign on Ti–6Al–4V. • Size effect assessment on fretting fatigue. • Investigation of volume and size of the slip areas on fretting fatigue resistance. • Size parameters do not have great influence on fretting fatigue resistance. [ABSTRACT FROM AUTHOR]

Adolescents are the focus of many interventions that aim to prevent HIV transmission. In order for these interventions to be effective, it is essential to understand adolescents' sexual behaviour. Using data collected in Yaoundé, Cameroon, in 1997, the study analysed risk exposure and HIV prevalence among 426 men and 510 women aged 15-24. Although risky behaviours seem to be more prevalent among young men, their HIV prevalence remains under 1%. In contrast, HIV prevalence is high among young women (7.5%), even those who report having had few sexual partners. Mixing patterns among sexual partners, and especially the age difference between men and women, do not seem to be sufficient to explain the large male-female discrepancy in HIV prevalence that is evident in these data. The results are therefore probably due to a greater susceptibility to infection of young women than men. This study highlights the necessity of reinforcing prevention campaigns among youth and fighting the obstacles that continue to impede the use of condoms in this population. [ABSTRACT FROM AUTHOR]

Introduction/Background For a same accelerometer, the manufacturer mentions that it can be worn at different positions on the body. However, we assume that the data are different according the accelerometer positions and the recorded activity. The aim of the study was to compare the energy expenditure values estimated by the Actigraph accelerometer according to accelerometer position on the body. Material and method Twenty-seven elderly (71 ± 4 years) volunteered to realize successively: 3 minutes computer-based word processing, 5 minutes biking (70 watts), 5 minutes walking (4.6 km/h) and 5 minutes running (5.8 km/h) on treadmill. The oxygen consumption was evaluated continuously by a gas analyzer (Metamax 3B). The energy expenditure was estimated by 3 accelerometers (Actigraph GT3X) worn on the hip, on the wrist and ankle on the dominant side (26 were right-handed and one was left-handed). Conclusion This study showed that for a same accelerometer positioned differently on the body, there are important differences in the energy expenditure estimation. This observation applies to both static and locomotor activities. Further works are necessary to find the best accelerometer position to estimate the energy expenditure in the elderly according to the activity. [ABSTRACT FROM AUTHOR]

Summary: Vaccine‐specific antibody responses are essential in the diagnosis of antibody deficiencies. Responses to Pneumovax II are used to assess the response to polysaccharide antigens, but interpretation may be complicated. Typhim Vi®, a polysaccharide vaccine for Salmonella typhoid fever, may be an additional option for assessing humoral responses in patients suspected of having an immunodeficiency. Here we report a UK multi‐centre study describing the analytical and clinical performance of a Typhi Vi immunoglobulin (Ig)G enzyme‐linked immunosorbent assay (ELISA) calibrated to an affinity‐purified Typhi Vi IgG preparation. Intra‐ and interassay imprecision was low and the assay was linear, between 7·4 and 574 U/ml (slope = 0·99–1·00; R2 > 0·99); 71% of blood donors had undetectable Typhi Vi IgG antibody concentrations. Of those with antibody concentrations  > 7·4 U/ml, the concentration range was 7·7–167 U/ml. In antibody‐deficient patients receiving antibody replacement therapy the median Typhi Vi IgG antibody concentrations were  < 25 U/ml. In vaccinated normal healthy volunteers, the median concentration post‐vaccination was 107 U/ml (range 31–542 U/ml). Eight of eight patients (100%) had post‐vaccination concentration increases of at least threefold and six of eight (75%) of at least 10‐fold. In an antibody‐deficient population (n = 23), only 30% had post‐vaccination concentration increases of at least threefold and 10% of at least 10‐fold. The antibody responses to Pneumovax II and Typhim Vi® correlated. We conclude that IgG responses to Typhim Vi® vaccination can be measured using the VaccZyme Salmonella typhi Vi IgG ELISA, and that measurement of these antibodies maybe a useful additional test to accompany Pneumovax II responses for the assessment of antibody deficiencies. [ABSTRACT FROM AUTHOR]

Equine viral arteritis (EVA) may have serious economic impact on the equine industry. For this reason, it is monitored in many countries, especially in breeding stock, to avoid its spread during breeding activities. In France, surveillance is mainly based on serological tests, since mares are not vaccinated, but difficulties in interpreting certain series of results may impair the estimation of the number of outbreaks. In this study, we propose specific rules for identifying seroconversion in order to estimate the number of outbreaks that were detected by the breeding stock surveillance component (BSSC) in France between 2006 and 2013. A consensus among multidisciplinary experts was reached to consider seroconversion as a change in antibody titer from negative to at least 32, or as an eight-fold or greater increase in antibody level. Using these rules, 239 cases and 177 outbreaks were identified. Subsequently, we calculated the BSSC’s sensitivity as the ratio of the number of detected outbreaks to the total number of outbreaks that occurred in breeding stock (including unreported outbreaks) estimated using a capture-recapture model. The total number of outbreaks was estimated at 215 (95% credible interval 195–249) and the surveillance sensitivity at 82% (CrI 95% 71–91). Our results confirm EVA circulation in French breeding stock, show that neutralizing antibodies can persist up to eight years in naturally infected mares and suggest that certain mares have been reinfected. This study shows that the sensitivity of the BSSC is relatively high and supports its relevance to prevent the disease spreading through mating. [ABSTRACT FROM AUTHOR]

Chronic mucocutaneous candidiasis (CMC) is characterized by recurrent and persistent superficial infections, with Candida albicans affecting the mucous membranes, skin and nails. It can be acquired or caused by primary immune deficiencies, particularly those that impair interleukin (IL)−17 and IL-22 immunity. We describe a single kindred with CMC and the identification of a STAT1 GOF mutation by whole exome sequencing (WES). We show how detailed clinical and immunological phenotyping of this family in the context of WES has enabled revision of disease status and clinical management. Together with analysis of other CMC cases within our cohort of patients, we used knowledge arising from the characterization of this family to develop a rapid ex-vivo screening assay for the detection of T helper type 17 (Th17) deficiency better suited to the routine diagnostic setting than established in-vitro techniques, such as intracellular cytokine staining and enzyme-linked immunosorbent assay (ELISA) using cell culture supernatants. We demonstrate that cell surface staining of unstimulated whole blood for CCR6+CXCR3-CCR4+CD161+ T helper cells generates results that correlate with intracellular cytokine staining for IL-17A, and is able to discriminate between patients with molecularly defined CMC and healthy controls with 100% sensitivity and specificity within the cohort tested. Furthermore, removal of CCR4 and CD161 from the antibody staining panel did not affect assay performance, suggesting that the enumeration of CCR6+CXCR3-CD4+ T cells is sufficient for screening for Th17 deficiency in patients with CMC and could be used to guide further investigation aimed at identifying the underlying molecular cause. [ABSTRACT FROM AUTHOR]

The article presents a study aimed to perform a retrospective analysis of contagious equine metritis (CEM) in France since 2006 for the purpose of determining its multilocus sequence typing (MLST) genotyping. The study is undertaken through considering thirty-eight (38) CEM cases confirmed by the French national reference laboratory. The results of the study found out that CEM case were generally sporadic.

B1 B cells represent a unique subset of B lymphocytes distinct from conventional B2 B cells, and are important in the production of natural antibodies. A potential human homologue of murine B1 cells was defined recently as a CD20+ CD27+ CD43+ cell. Common variable immunodeficiency ( CVID) is a group of heterogeneous conditions linked by symptomatic primary antibody failure. In this preliminary report, we examined the potential clinical utility of introducing CD20+ CD27+ CD43+ B1 cell immunophenotyping as a routine assay in a diagnostic clinical laboratory. Using a whole blood assay, putative B1 B cells in healthy controls and in CVID patients were measured. Peripheral blood from 33 healthy donors and 16 CVID patients were stained with relevant monoclonal antibodies and underwent flow cytometric evaluation. We established a rapid, whole blood flow cytometric assay to investigate putative human B1 B cells. Examination of CD20+ CD27+ CD43+ cells is complicated by CD3+ CD27+ CD43hi T cell contamination, even when using stringent CD20 gating. These can be excluded by gating on CD27+ CD43lo-int B cells. Although proportions of CD20+ CD27- CD43lo-int cells within B cells in CVID patients were decreased by 50% compared to controls ( P < 0·01), this was not significant when measured as a percentage of all CD27+ B cells ( P = 0·78). Immunophenotypic overlap of this subset with other innate-like B cells described recently in humans is limited. We have shown that putative B1 B cell immunophenotyping can be performed rapidly and reliably using whole blood. CD20+ CD27+ CD43lo-int cells may represent a distinct B1 cell subset within CD27+ B cells. CVID patients were not significantly different from healthy controls when existing CD27+ B cell deficiencies were taken into account. [ABSTRACT FROM AUTHOR]

Common variable immunodeficiency disorders (CVID) are a group of heterogeneous conditions that have in common primary failure of B cell function, although numerous T cell abnormalities have been described, including reduced proliferative response and reduced regulatory T cells. This study compared the T cell phenotype of CVID patients subdivided into clinical phenotypes as well as patients with partial antibody deficiencies [immunoglobulin (Ig)G subclass deficiency and selective IgA deficiency], X-linked agammaglobulinaemia (XLA) and healthy and disease controls. Absolute numbers of T cell subpopulations were measured by four-colour flow cytometry: naive T cells, central and effector memory and terminally differentiated (TEM) T cells, using CD45RA and CCR7 expression. Early, intermediate and late differentiation status of T cells was measured by CD27/CD28 expression. Putative follicular T cells, recent thymic emigrants and regulatory T cells were also assessed. Significant reduction in naive CD4 T cells, with reduced total CD4 and recent thymic emigrant numbers, was observed in CVID patients, most pronounced in those with autoimmune cytopenias or polyclonal lymphoproliferation. These findings suggest a lack of replenishment by new thymically derived cells. CD8 naive T cells were reduced in CVID patients, most significantly in the autoimmune cytopenia subgroup. There was a reduction in early differentiated CD4 and CD8 T cells and increased CD8 TEM in the CVID patients, particularly autoimmune cytopenia and polyclonal lymphoproliferation subgroups, suggesting a more activated T cell phenotype, due perhaps to an antigen-driven process. XLA patients had significantly reduced putative follicular T cells, which may depend on B cells for survival, while no significant alterations were observed in the T cells of those with IgG subclass deficiency or selective IgA deficiency. [ABSTRACT FROM AUTHOR]

The present study aimed to create a direct bridge between observations on peripheral and central responses to odorant mixtures and their components. Three experiments were performed using mixtures of fruity (isoamyl acetate; ISO) and woody (whiskey lactone; WL) odorants known to contribute to some of the major notes in Burgundy red wine. These experiments consisted of (i) calcium imaging of human embryonic kidney cells (HEK293T) transfected with olfactory receptors (ORs); (ii) single-unit electrophysiological recordings from olfactory receptor neurons (ORNs) and analyses of electro-olfactogram (EOG) responses in the rat nose in vivo; and (iii) psychophysical measurements of the perceived intensity of the mixtures as rated by human subjects. The calcium imaging and electrophysiological results revealed that ISO and WL can act simultaneously on single ORs or ORNs and confirm that receptor responses to mixtures are not the result of a simple sum of the effects of the individual mixture compounds. The addition of WL to ISO principally suppressed the ORN activation induced by ISO alone and was found to enhance this activation in a subset of cases. In the human studies, the addition of high concentrations of WL to ISO decreased the perceived intensity of the ISO. In contrast, the addition of low concentrations of WL enhanced the perceived intensity of the fruity note (ISO) in this mixture, as it enhanced EOG responses in ORNs. Thus, both OR and ORN responses to ISO + WL mixtures faithfully reflected perceptual response changes, so the odour mixture information is set up after the peripheral stage of the olfactory system. [ABSTRACT FROM AUTHOR]

Paraproteinaemia following allo-SCT is common. We analysed 91 consecutive patients undergoing allo-SCT; conditioning included alemtuzumab in 42% of the patients. Paraproteinaemia incidence at 2 years was 32%. In univariate analysis paraproteinaemia was associated with unrelated donor, age, recipient seropositivity for CMV and alemtuzumab conditioning (hazard ratio (HR) 3.93, P=0.0006). Paraproteinaemia was not associated with haematological diagnosis; disease status at transplant; varicella zoster, herpes simplex or EBV serology; reduced-intensity vs myeloablative conditioning or GVHD. CMV reactivation-more frequent in alemtuzumab recipients-was associated with paraproteinaemia (HR 7.52, P<0.0001). In multivariate analysis, only increasing age (HR 1.04 per year, P=0.048) and CMV reactivation (HR 5.74, P=0.001) were significantly associated with paraproteinaemia. Alemtuzumab without CMV reactivation, however, resulted in significantly more paraproteinaemia, suggesting an effect that is independent of CMV reactivation. OS was poorer in patients with paraproteinaemia (HR 2.54, P=0.04) and relapse increased (HR 2.38, P=0.087). Paraproteinaemia was not significantly independently associated with decreased survival on multivariate analysis. Post transplant paraproteinaemia is associated with CMV reactivation, is more frequent in alemtuzumab-conditioned transplants and is not associated with improved OS. [ABSTRACT FROM AUTHOR]

Common variable immunodeficiency disorders (CVIDs) are a heterogeneous group of diseases characterized by hypogammaglobulinaemia and consequent susceptibility to infection. CVID patients commonly develop a variety of additional manifestations for which the causative factors are not fully understood. Two such manifestations are granulomatous disease and enteropathy. Because the ability to predict complications would aid clinical management, we continue to search for possible disease modifier genes. NOD2 acts a microbial sensor and is involved in proinflammatory signalling. Particular mutations of the NOD2 gene are associated with Crohn's disease including gly908arg, leu1007finsc and arg702trp polymorphisms. We hypothesized that NOD2 polymorphisms may be a disease modifier gene towards an enteropathic or granulomatous phenotype within CVIDs. Sequence-specific primers returned genotypes for 285 CVID patients from centres across the United Kingdom and Europe. We present the frequencies of the different phenotypes of patients within our international cohort. Arg702trp polymorphisms were significantly less frequent than wild-type (WT) ( P = 0·038) among international CVID patients with splenomegaly. Gly908arg polymorphisms were more prevalent than WT in UK patients with autoimmune disorders ( P = 0·049) or enteropathy ( P = 0·049). NOD2 polymorphisms were not more prevalent than WT in CVID patients with clinical phenotypes of granulomata. UK allele frequencies of 0·014, 0·056 and 0·026 were found for gly908arg, arg702trp and leu1007finsc NOD2 polymorphisms, respectively. These do not differ significantly from UK immunocompetent controls confirming, as expected, that in addition these NOD2 polymorphisms do not confer susceptibility to CVIDs per se. [ABSTRACT FROM AUTHOR]

Background: Obstructive sleep apnoea syndrome (OSAS) has been associated with cardiovascular disease in epidemiological and observational studies. Continuous positive airway pressure (CPAP) is the treatment of choice for OSAS, but the impact of this intervention on systemic inflammation involved in the atherosclerotic process remains unclear. Methods: 100 men with moderate-severe OSAS were randomised to therapeutic (n = 51) or subtherapeutic (n = 49) CPAP treatment for 4 weeks to investigate the effects of active treatment on inflammatory markers such as highly sensitive C reactive protein (hsCRP), interleukin (IL)6, interferon γ (IFNγ) and anti-inflammatory adiponectin. Results: 4 weeks of therapeutic CPAP did not significantly change blood levels of hsCRP compared with the subtherapeutic control group (difference between median changes -0.24 mg/l (95% CI -0.88 to +0.24); p = 0.30). Plasma levels of IL6 and IFNγ did not change significantly following therapeutic compared with subtherapeutic CPAP (difference between median changes +0.52 and -0.07 pg/ml (95% CI -0.72 to +1.94 and -0.81 to +0.44); p = 0.45 and p = 0.82, respectively). Furthermore, 4 weeks of therapeutic CPAP did not significantly change levels of adiponectin in plasma compared with the subtherapeutic control group (difference between median changes +0.05 pg/ml (95% CI -0.36 to +0.47); p = 0.84). If patients with hsCRP values above 8 mg/l at baseline were excluded, differences between the changes in hsCRP, IL6, IFNγ and adiponectin after 4 weeks of CPAP were smaller, and again not statistically different between groups. Conclusions: 4 weeks of CPAP treatment has no beneficial effect on blood markers of inflammation and adiponectin in patients with moderate-severe obstructive sleep apnoea. [ABSTRACT FROM AUTHOR]

CD45, the leucocyte common antigen, is a haematopoietic cell specific tyrosine phosphatase. Human polymorphic CD45 variants are associated with autoimmune and infectious diseases and alter the phenotype and function of lymphocytes, establishing CD45 as an important regulator of immune function. Here we report four patients with diverse diseases with unusual clinical features. All four have the C77G polymorphism of CD45 exon 4, which alters the splicing and CD45RA/CD45R0 phenotype of lymphocytes. We suggest that C77G may be a contributing factor in these unusual cases. [ABSTRACT FROM AUTHOR]

This study describes an in vitro model of peripheral blood mononuclear cell (PBMC) migration through human endothelial cells, held on polycarbonate inserts, which allows automatic differential counting of migrated cells as lymphocytes and monocytes. Using this system it was found that treatment of PBMC with the phosphodiesterase (PBMC) inhibitors theophylline (at 1 and 10 μg. ml) and RO-20-1724 (at I μM) inhibited the migration of the lymphocyte component to 64.2 ±16.4%. 48.9 ± 3.0% and 47.5 ± 5.8% of the control values. respectively, while the migration of the monocytes component was largely unaffected. The POE inhibitors needed to be present during the assay to inhibit migration, whereas pie-treatment of either the endothelium or the PBMC did not consistently effect lymphocyte migration. The drugs also inhibited the migration of lymphocytes through control inserts, either uncoated or coated with fibronectin. suggesting that some of the inhibition is an effect on lymphocyte motility rather than lymphocyte endothetial interact ions. Lymphocyte migration through fibronectin-coated filters was significantly enhanced compared with uncoated filters. Activation of the PBMC by anti-CD3 MoAb increased motility and migration by tip to 300%. This migration appeared to be greatly inhibited by the PDE inhibitors, although the effect was complicated by problems of lymphocyte aggregation. This study provides a novel method of measuring mononuclear cell transendothelial migration. and suggests a possible role of PDE inhibitors in reducing this Process. [ABSTRACT FROM AUTHOR]

The core of the French equine traceability system is the census database (SIRE) managed by the French horse and riding institute (IFCE). Following the death of an equine, owners are legally obliged to take charge of cadaver removal by contacting a rendering company directly or after registration on the national ATM-équidés ANGEE association (ATM) website, which proposes negotiated prices for removal and recording of the death in the SIRE database. Despite these offers, ATM notes few users. Owners are also legally obliged to return the equine's passport to the IFCE, but only 30–40 % of owners comply with the regulation. Rendering companies register data on equine mortality in the fallen stock data interchange database (FSDI), but it is difficult to cross-reference these data with SIRE data. Consequently, the death of equines is not well registered in the SIRE database. The objective of the present study was to identify levers that could be used to improve dead equine traceability by i) investigating the level of satisfaction of equine owners with ATM and rendering company services; and ii) investigating the drawbacks of owners having to return the passport to the IFCE. An online survey was designed and distributed by email to the 5 158 owners who used ATM services between April 2017 and April 2018. The response rate was 16.4 %. Most owners were satisfied by ATM and rendering company services. The lack of simple and quick removal procedures and the lack of any connection between ATM and the rendering companies were among the main drawbacks identified. Regarding the return of the passport to the IFCE, most responding owners returned it through the rendering company (65 %) or directly (2 %). The passport was returned significantly more frequently when requested by the renderers. The main reason for not providing the passport was the owner wanted to keep it as a souvenir. These results suggest that ATM and the rendering companies are key players in dead equine traceability. ATM services should be developed through the establishment of a direct connection with rendering companies to accelerate the cadaver removal request and to allow the cross-referencing of data between the ATM, FSDI and SIRE databases for a better dead equine traceability. Rendering companies need regulatory support to help them ask owners for the equine's passport, formalizing their contribution to equine traceability. Finally, effective communication has to be established to inform owners about the removal procedures and the regulations. [ABSTRACT FROM AUTHOR]

Examines the immunocytochemical staining of breast carcinoma using the monoclonal antibody NCRC 11. Process of staining; Relationship between the intensity of staining and patient survival; Predictors of the prognosis in patients with operable breast cancer.

Examines the staining of breast cancer with NCRC 11, a monoclonal antibody. Assessment of tumor samples embedded in paraffin; Relation between the intensity of staining and patient survival; Factors indicating the prognosis of the patient.

Deals with a study which described the evolution of the electromyogram signal during tiring dynamic exercise. Materials and methods; Results; Discussion.