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Summary: Adaptor chimeric antigen receptor (CAR) T‐cell therapy offers solutions for improved safety and antigen escape, which represent main obstacles for the clinical translation of CAR T‐cell therapy in myeloid malignancies. The adaptor CAR T‐cell platform 'UniCAR' is currently under early clinical investigation. Recently, the first proof of concept of a well‐tolerated, rapidly switchable, CD123‐directed UniCAR T‐cell product treating patients with acute myeloid leukaemia (AML) was reported. Relapsed and refractory AML is prone to high plasticity under therapy pressure targeting one single tumour antigen. Thus, targeting of multiple tumour antigens seems to be required to achieve durable anti‐tumour responses, underlining the need to further design alternative AML‐specific target modules (TM) for the UniCAR platform. We here present the preclinical development of a novel FMS‐like tyrosine kinase 3 (FLT3)‐directed UniCAR T‐cell therapy, which is highly effective for in vitro killing of both AML cell lines and primary AML samples. Furthermore, we show in vivo functionality in a murine xenograft model. PET analyses further demonstrate a short serum half‐life of FLT3 TMs, which will enable a rapid on/off switch of UniCAR T cells. Overall, the presented preclinical data encourage the further development and clinical translation of FLT3‐specific UniCAR T cells for the therapy of AML. [ABSTRACT FROM AUTHOR]

Many environmental factors influence the concentration of total serum IgE (tIgE); however, tIgE synthesis is believed to be under strong genetic influence. Multiple genetic studies on tIgE regulation have been performed. For these population-based studies tIgE was commonly determined at one time-point, assuming that tIgE phenotypes (adjusted for age and gender) are stable over time.We assessed correlations of tIgE levels from birth to the age of 10 years in the birth cohort MAS (Multicenter Allergy Study;n=1314).We determined cord-blood IgE levels, total and specific IgE at the age of 1, 2, 3, 5, 6, 7, and 10 years. Spearman correlation coefficients were calculated for tIgE at different time-points. All analyses were performed in the entire cohort, adjusted for gender, as well as in non-atopic children only.tIgE percentiles increased steadily from birth to the age of 10 years with higher values for boys than for girls at each time-point. tIgE values from birth to 3 years of age correlated poorly with tIgE levels at 10 years (r<0.5). However, good correlations (r>0.8) were observed for tIgE concentrations at 6, 7 and 10 years. The same results were observed when the analyses were limited to non-atopic children.In childhood, tIgE levels underlie remarkable variation over time even in the absence of atopy. For cross-sectional population-based genetic and epidemiologic studies, tIgE values of children<5 years should be interpreted with caution since these values correlate poorly with tIgE levels later in life. [ABSTRACT FROM AUTHOR]

Examines amorphous hydrogenated silicon/crystalline silicon (a-Si:H/c-Si) heterojunction solar cells with regard to efficiency and simplicity of processing. Discussion of the fabrication steps of our a-Si:H/c-Si technology and analysis of the electronic device properties by quantum efficiency, current-voltage, admittance, and capacitance-voltage measurements; Impact of crystalline Si absorber on the open-circuit voltage and the fill factor of the a-Si:H/c-Si heterojunction solar cells; Recombination at the amorphous hydrogenated silicon/crystalline silicon-interface is subsidiary in respect of the limitation of the open-circuit voltage. Data suggesting the n-type a-Si:H/p-type c-Si solar cell prepared without high-efficiency features such as back-surface field or surface texturing has an independently confirmed efficiency of 14.1 percent.

Background Atopic family history and cord blond IgE have been used as predictors of atopic disease in newborns for about 20 years, but at least. For cord blood IgE the sensitivity has been shown to be very low, The objective of this paper was to evaluate whether parental history and cord blood-IgE were more accurate predictors for the appropriate atopic phenotypes in the infants rather than for any atopy. Methods A total of I 3 I 4 newborn infants was recruited in six German obstetric departments in 1990 and followed-up for 2 years. Four hundred and ninety-nine (38%) were at high risk for atopy with at least two first degree atopic family members and/or elevated cord-blood IgE concentrations. Results The cumulative incidence of atopic dermatitis over the first 2 years of life (AD24) amounted to 20.1%, and there was a significant association with AD history of the mother (OR 2.5, 95%CI 1.46-4.26) and of the father (OR 3.33. 95% Cl 1.90-6.54). The cumulative incidence of recurrent wheezing in the first 2 years of life (RW24) amounted to 16.1%, and was positively associated with asthma history (OR 2.11, 95%CI 1.33-3.60) and sensitization history (OR 1.64, 95%CI 1.34-2.36) of the mother, but with neither for the father. RW24 was less prevalent in girls than in boys (OR 0.64, 95%CI 0.47-0.89). Thirty-one per cent of infants were sensitized (CAP test value >0.35 kU/L) against at least one of nine food or inhalative allergens (S24) and this was significantly associated with cord blood-IgE value (OR 2.43, 95%CI 1.69-3.49), and sensitization history of the mother (OR 1.64, 95%CI 1.18-2.41). Using multiple logistic regression analysis, the prediction of AD24 by AD of parents, of RW24 by asthma of parents, and of sensitization by cord blood lgE was of low accuracy. Conclusion The predictive capacity of parental history and cord blood IgE is not high enough to recommend them as screening instruments for primary prevention. The majority of atopic manifestations and of sensitization occur in infants with no demonstrable risk at birth. [ABSTRACT FROM AUTHOR]

Cites a study which focused on the risk of developing atopic manifestations following exposure in the newborn. General agreement that atopic manifestations depend upon genetic and environmental factors; Reference to studies which suggest that avoidance of alimentary allergens in early infancy and possibly during pregnancy may have favorable effects on the natural course of atopic disease; Debate over the justification for neonatal screening for the risk of atopic diseases.

Our aim was to study the influence of infection with the respiratory syncytial virus (RSV) in non-hospitalized infants on sensitization to aeroallergens and the early manifestation of atopy. Six hundred and nine infants from the prospective German Multicenter Cohort Study on Atopy were included, 38% of whom had an elevated atopic risk. RSV IgG and IgM antibodies were tested by ELISA with gradient purified RSV antigen. Specific IgE against mites, cat dandruff, birch and grass pollens and relevant nutritional antigens were tested with CAP-RAST-FEIA (Pharmacia, Sweden). Of the cord sera 99% were positive for RSV-IgG, 44.7% at one year and 64.2% (n=265) at two years of age. The positivity rate after 12 months varied with the season of birth, the number of siblings and the degree of exposure to tobacco smoke; and correlated closely with attacks of wheezing during infancy. Twenty (2.8%) children were found to be sensitized against at least one aeroallergen at one year, and 28 (10.5%) at two years. By the first birthday, mite sensitization (n=3) could only be seen in the RSV-infected children; grass pollen sensitization (n=9) was associated with RSV seropositivity (logistic regression model including the confounders mentioned above: with RSV IgG and IgM ), as was birch sensitization (n=5) with RSV IgM (p=0.009). No such differences could be detected at two years. No correlation of RSV seropositivity to any allergic manifestation could be found. We conclude, that it is only in the first year of life, that RSV infection plays a significant role in promoting sensitization against aeroallergens, which do not at this time produce allergic symptoms. [ABSTRACT FROM AUTHOR]

In order to identify newborns at risk for atopic diseases, we developed a family questionnaire and selected specific answers which were suitable to identify atopic family members. The validity of the questionnaire was evaluated by the Phadiatop test results of 793 mothers and 353 fathers. As both screening instruments do not measure the same, the Phadiatop test identifies sensitization to inhalant allergens and the history reflects the clinical manifestation of atopic disease, the agreement between sensitization and manifestation is incomplete. Sensitivity and specificity of the questionnaire screening conditions to reproduce the Phadiotop test result was 64% and 84% for mothers, and 58% and 88% for fathers, respectively. The relative risk for lifetime prevalence of atopic manifestations in Phadiatop positive over negative mothers was calculated to be 3.88 (95% confidence interval = 3.12 to 4.81), and for Phadiatop positive over negative fathers to amount 4.84 (95% confidence interval 3.25 to 7.23). A few relevant answers of 20 were identified by logistic regression analysis to predict the Phadiatop test result nearly, as well as the total questionnaire. [ABSTRACT FROM AUTHOR]

Background: The study aimed to assess the effect of pre‐ and postnatal tobacco smoke exposure on specific sensitization to food allergens and inhalant allergens during the first 3 years of life. Methods: A total of 342 children of a prospective and observational birth cohort study on atopy (MAS) were included on the basis of a complete follow‐up of specific IgE measurements at the ages of 1, 2, and 3 years with available questionnaire information about the parental smoking habit at birth, 18 months, and 3 years of age. Study children were grouped into four exposure categories representing in utero and postnatal environmental tobacco smoke (ETS) exposure, and according to the number of cigarettes smoked by the parents. The effect on the development of allergic sensitization to food, outdoor, and indoor allergens by 3 years of age was determined by multiple logistic regression analyses. Results: At the age of 3, children who were pre‐ and postnatally exposed to tobacco smoke had a significantly higher risk of sensitization to food allergens (odds ratio: 2.3, 95% C.I.: 1.1–4.6) than unexposed children. Children who were only postnatally exposed by a smoking mother also had a 2.2 times higher risk (95% C.I.: 0.9–5.9) of sensitization than unexposed children. These two categories (pre‐ and/or postnatal exposure) contribute to the significant overall effect of the tobacco smoke exposure (P≤0.02). No significant association between tobacco smoke exposure and specific sensitization to inhalant allergens was observed. The determining risk factors for this type of sensitization were atopic family history and mite‐ and cat‐allergen exposure levels. Conclusions: During the first 3 years of life, both prenatal and postnatal tobacco smoke exposure has an adjuvant effect on allergic sensitization which seems to be restricted to allergens to which children are mainly exposed, in combination with the peak of the ETS... [ABSTRACT FROM AUTHOR]

For screening atopy risk in 6401 (84%) of all infants born during the year 1990 in six Obstetric, departments of five German cities; cord-blood IgE values were determined with CAP-RAST-FEIA. After cases with elevated IgA values had been excluded, 25% of the values were above the detection limit of 0.35 kU/l, and 8.5% were above 0.9 kU/l. Boys had significantly higher values than girls (P< 0.001). The distribution of values was significantly different for different nationalities of mothers (P < 0.001). The percentage of elevated values (>0.9 kU/l) increased significantly with the number of close family members with atopic history (P < 0.001). Regarding the atopic history of the father, siblings, and mother separately, only the mother's history had a significant association with the cord-blood IgE class (P < 0.001) The IgE values of 81 twin pairs correlated significantly with a coefficient of r = 0.4909 (P &lt 0.001). The smoking history of the parents during pregnancy showed an association with cord-blood IgE values (P < 0.02). No significant association could be shown between cord-blood IgE distribution and other variables, i.e., gestational age, birth size, birth modus, Apgar score, cord-blood pH value, neonatal problems, parity, age of the mother; medication during pregnancy, educational level of mother or father, time of year, or obstetric department It is hypothesized that, in addition to some postpartum contamination or placental transfer of maternal IgE, cord-blood IgE values are also determined by the fetal immunologic reaction to intrauterine exposure to allergens and trigger factors, and by genetic influences, [ABSTRACT FROM AUTHOR]

Background The results of numerous studies on the influence of breastfeeding in the prevention of atopic disorders are often contradictory. One of the most important problems is confounding by other lifestyle factors. Objective The aim of the present study was to analyse the effect of any breastfeeding duration on the prevalence of atopic eczema in the first seven years of life taking into account other risk factors. Methods In an observational birth cohort study 1314 infants born in 1990 were followed-up for seven years. At 3, 6, 12, 18, 24 months and every year thereafter, parents were interviewed and filled in questionnaires, children were examined and blood was taken for in vitro allergy tests. Generalized Estimation Equations (GEE)-models were used to model risk factors for the prevalence of atopic eczema and for confounder adjustment Results Breastfeeding was carried out for longer if at least one parent had eczema, the mother was older, did not smoke in pregnancy, and the family had a high social status. The prevalence of atopic eczema in the first seven years increased with each year of age (OR 1.05; 95% CI 1.01–1.09 for each year), with each additional month of breastfeeding (1.03; 1.00–1.06 for each additional month), with a history of parental atopic eczema (2.06; 1.38–3.08), and if other atopic signs and symptoms appeared, especially specific sensitization (1.53; 1.25–1.88), and asthma (1.41; 1.07–1.85). Although breastfeeding should be recommended for all infants, it does not prevent eczema in children with a genetic risk. Conclusion Parental eczema is the major risk factor for eczema. But in this study, each month of breastfeeding also increased the risk. [ABSTRACT FROM AUTHOR]

Unlabelled: The biology of human milk and lactation helps understand the physiology of breastfed infants. The compositional and biological effects of human milk lipids have received considerable interest regarding their modulating effects on growth, metabolism and functions of the cardiovascular, immune and nervous system., Conclusion: This paper describes key aspects of a scientific workshop focused on current knowledge, unresolved questions and future research needs in the area of human milk lipids and their physiological effects in infants., (© 2011 The Author(s)/Acta Paediatrica © 2011 Foundation Acta Paediatrica.)