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Background Atopic dermatitis (AD) is a chronic inflammatory skin disease with a multifactorial genesis including genetic predispositions and environmental risk and trigger factors. One of the latter possibly is smoking, indicated by an increased prevalence of AD in adults and children that are actively or passively exposed to cigarette smoke. Objectives In this study AD characteristics and its atopic comorbidities are compared in smoking and nonsmoking AD patients. Methods TREATgermany is a non-interventional clinical registry which includes patients with moderate to severe AD in Germany. Baseline data of patients included into TREATgermany from inception in June 2016 to April 2020 in 39 sites across Germany was analyzed comparing AD disease characteristics and comorbidities in smokers versus non-smokers. Results Of 921 patients, 908 (male: 58.7%) with a mean age of 41.9 ± 14.4 reported their smoking status. The objective Scoring of Atopic Dermatitis (oSCORAD) did not differ between smokers (n=352; 38.8%) and nonsmokers, however lesions' intensity of oozing/crusts and excoriations as well as patient global assessment scores (PGA) of AD severity were higher in smoking as opposed to nonsmoking patients. Smokers reported a lower number of weeks with well-controlled AD and more severe pruritus than nonsmokers. Total IgE levels were more elevated in smokers and they displayed a younger age at initial diagnosis of bronchial asthma. After adjustment for potential confounders, the increased intensity of oozing/crusts, the reduced number of weeks with well-controlled AD and the greater pruritus remained different in smokers compared to nonsmokers. In addition, smoking patients with adult-onset AD showed a 2.5 times higher chance of involvement of the feet. Conclusions German registry data indicate that AD patients who smoke have a higher disease burden with a different distribution pattern of lesions in adult-onset AD.

BACKGROUND Atopic dermatitis (AD) is a chronic inflammatory skin disease characterized by unrelenting pruritus and recurrent eczematous lesions. It affects up to 15% of children and adolescents and up to 5% of adults, and confers a high and multifactorial burden to patients, families and society. With increasing awareness of this substantial burden, AD has become a priority for healthcare systems. AIM The Atopic Dermatitis Quality of Care (ADQoC) initiative set out to describe good practices for addressing the challenges that impede the management of AD. METHODS The initiative carried out a literature review and surveyed 32 expert care centres, catalogued findings, and analysed and elucidated global challenges to AD care along with good practice implementations that can address them. RESULTS The four challenges to quality care for AD are: (i) misconceptions about AD; (ii) delayed referral and access to AD specialists; (iii) poor patient access to AD treatments and poor adherence to medications; and (iv) managing the complexity of AD and its comorbidities. The initiative highlighted 5 of 10 good practice implementations as high priority for any AD care centre to focus on: (i) clinical assessment and diagnosis; (ii) a structured multidisciplinary care team; (iii) monitoring and evaluating care quality; (iv) patient education and communication; and (v) collaboration and exchange with patient groups. CONCLUSION These implementations can provide benefits for patients, healthcare providers and the healthcare system. They directly contribute to the efficacy of treatment, improved healthcare provider efficiency, improved education for patients and healthcare providers, and improved costs to healthcare systems. The initiative was launched on https://atopicdermatitiscare.kpmg.co.uk/ to provide an easy-to-use educational platform.

With AtopicHealth1, the first national care study on atopic dermatitis (AD) was conducted in 2010. At that time, about one third of the patients undergoing treatment by dermatologists showed severe limitations in quality of life, which indicated an insufficient quality of care. The aim of the present study was to characterise the current care of patients with AD undergoing dermatological treatment in comparison between different severity grades, as well as in comparison to 2010 and to psoriasis.The Germany-wide multicentre cross-sectional study "AtopicHealth2" recorded clinical data, quality of life (DLQI), therapies, preventive behaviour and patient-defined treatment benefit (PBI). Patients with an indication for systemic therapy were considered moderately to severely affected for subgroup analyses, the others mildly affected.Between 2017 and 2019, 1291 patients (median age 41 years, 56.5% female) were enrolled by 111 centres. Compared with 2010, there were no improvements in quality of life (DLQI 8.5 in both studies), severity (SCORAD 45.4 vs. 42.3 in 2010) or treatment benefit (PBI 2.2 vs. 2.4 in 2010). Moderately to severely affected patients were more likely to show impaired quality of life (45.4% vs. 23.6%) and less likely to have relevant treatment benefits (PBI 1: 21.3% vs. 13.2%) than mildly affected patients. In contrast to psoriasis, patients with AD revealed higher quality of life limitations (DLQI 8.5 vs. 6.1) and lower treatment benefit (PBI 2.2 vs. 2.8).Compared to 2010, there is no improvement in the quality of care for AD in Germany. Compared to psoriasis, patients with AD show higher burden and lower treatment benefit, which underlines the need for therapeutic innovations.HINTERGRUND: Mit AtopicHealth1 wurde 2010 die erste nationale Versorgungsstudie zur AD durchgeführt. Damals zeigte etwa ein Drittel der Patienten, die sich in einer Behandlung bei Dermatologen befanden, starke Einschränkungen der Lebensqualität, was auf eine unzureichende Versorgungsqualität hindeutete. Ziel der vorliegenden Studie war die Charakterisierung der aktuellen Versorgung von Patienten mit Neurodermitis in dermatologischer Behandlung im Schweregradvergleich sowie im Vergleich zu 2010 und zu Psoriasis.Die deutschlandweite multizentrische Querschnittstudie „AtopicHealth2“ erfasste klinische Daten, Lebensqualität (DLQI), Therapien, präventives Verhalten und patientendefinierten Behandlungsnutzen (PBI). Patienten mit einer Indikation für Systemtherapie wurden für Subgruppenanalysen als mittelschwer bis schwer, die anderen als leicht betroffen angesehen.Zwischen 2017 und 2019 wurden 1291 Patienten durch 111 Zentren eingeschlossen, mittleres Alter 41 Jahre, 56,5 % weiblich. Im Vergleich zu 2010 fanden sich keine Verbesserungen hinsichtlich Lebensqualität (jeweils DLQI 8,5), Schweregrad (SCORAD 45,4 vs. 42,3 in 2010) und Therapienutzen (PBI 2,2 vs. 2,4 in 2010). Mittelschwer bis schwer betroffene Patienten zeigten häufiger Lebensqualitätseinbuße (45,4 % vs. 23,6 %) und seltener relevante Therapienutzen (PBI 1: 21,3 % vs. 13,2 %) als leichter betroffene. Verglichen mit Psoriasis offenbarten die Patienten mit Neurodermitis höhere Lebensqualitätseinschränkungen (DLQI 8,5 vs. 6,1) und einen geringeren Behandlungsnutzen (PBI 2,2 vs. 2,8).Im Vergleich zu 2010 zeigt sich keine verbesserte Versorgungsqualität von Neurodermitis in Deutschland. Im Vergleich zur Psoriasis weisen Patienten mit Neurodermitis höhere Belastungen und geringere therapeutische Nutzen auf, was den Bedarf an therapeutischen Innovationen unterstreicht.

The coronavirus disease 2019 (COVID-19) pandemic is caused by rapid spread of different strains of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). The severity of infection ranges from mild, or even asymptomatic, to very severe. Signs and symptoms include fatigue, fever, exanthemas, upper respiratory illness, loss of smell and taste, pneumonia, severe acute respiratory syndrome, and multi-organ failure. Risk factors for a severe or lethal course include age, male gender, obesity, diabetes, cardiovascular disease, and immune suppression1 .

TREATgermany is a multicenter academic registry for the long-term observation of patients with moderate-to-severe atopic dermatitis (AD). Eligibility criteria, study procedures, and baseline characteristics including previous treatments have already been described (1). AD is associated with psychosocial disorders such as depression, anxiety, and suicidal ideation (2-4).

Since the introduction of active vaccination against SARS-CoV-2 infection, there has been a debate about the risk of developing severe allergic or anaphylactic reactions among individuals with a history of allergy. Indeed, rare cases of severe allergic reactions have been reported in the United Kingdom and North America. By february 2021 a rate of 4,5 severe allergic reactions occurred among 1 million patients vaccinated with the mRNA-based COVID-19 vaccines, which is higher than the generally expected rate of severe allergic reactions to vaccinations of around 1 in 1 million.

Chronic obstructive pulmonary disease (COPD) is a frequent diagnosis in older individuals and contributor to global morbidity and mortality. Given the link between lung disease and aging, we need to understand how molecular indicators of aging relate to lung function and disease. Using data from the population-based KORA (Cooperative Health Research in the Region of Augsburg) surveys, we associated baseline epigenetic (DNA methylation) age acceleration with incident COPD and lung function. Models were adjusted for age, sex, smoking, height, weight, and baseline lung disease as appropriate. Associations were replicated in the Normative Aging Study. Of 770 KORA participants, 131 developed incident COPD over 7 years. Baseline accelerated epigenetic aging was significantly associated with incident COPD. The change in age acceleration (follow-up - baseline) was more strongly associated with COPD than baseline aging alone. The association between the change in age acceleration between baseline and follow-up and incident COPD replicated in the Normative Aging Study. Associations with spirometric lung function parameters were weaker than those with COPD, but a meta-analysis of both cohorts provide suggestive evidence of associations. Accelerated epigenetic aging, both baseline measures and changes over time, may be a risk factor for COPD and reduced lung function.

Background The Atopic Dermatitis (AD) TREATgermany registry was initiated by the German Society for Dermatology (DDG) in 2011 to evaluate the ‘real‐life’ situation of health care for patients with AD. Objectives Interim data analysis on baseline characteristics as well as current and prescribed systemic treatments of the TREATgermany registry patients. Methods Patients (≥18 years) with moderate‐to‐severe AD [objective (o)SCORAD > 20], or with current or previous anti‐inflammatory systemic treatment for AD within 24 months, were included and are followed up over at least 24 months. To assess clinical signs, the eczema area severity index (EASI, 0–72), the oSCORAD (0–83) and the Investigator Global Assessment (IGA; 6‐point scale) were used. The disease severity was globally scored by the patients [Patient Global Assessment (PGA); six‐step Likert scale]. Disease symptoms were assessed by the patient‐oriented eczema measure (POEM, 0–28) and numeric rating scales (NRS, 0–10). Health‐related quality of life was measured using the dermatological life quality index (DLQI, 0–30). Results A total of 612 patients were recruited across 32 sites between 06/2016 and 01/2019 (mean age: 42.6 ± 14.2 years; mean oSCORAD: 40.8 ± 16.3). The mean POEM score was 16.3 ± 7.5. Pruritus was rated highest among subjective symptoms (NRS: 5.4 ± 2.7). The mean DLQI value was 11.3 ± 7.5. The frequency of arterial hypertension was lower (20.8%) compared with the general population, whilst this was higher for depression (10%). More than 60% of the patients had received systemic glucocorticosteroids, and 36.8% had received cyclosporine A prior to inclusion. Dupilumab was the leading substance documented as either ‘current’ (12.1%) or ‘prescribed’ (31.4%) at baseline. Conclusions These ‘real‐life’ data clearly demonstrate the substantial disease burden. Most of TREATgermany patients were already treated with or prescribed dupilumab at baseline. Moreover, current findings indicate the urgent need for further alternative agents in order to achieve a perceptible improvement of quality of life of patients with moderate‐to‐severe AD.

Atopic dermatitis (AD) is a complex disease with elevated risk of respiratory comorbidities.1,2 Severely affected patients are often treated with immune-modulating systemic drugs.3,4 On March 11th 2020, the World Health Organization declared the 2019 novel coronavirus severe acute respiratory syndrome (SARS-Cov-2) epidemic to be a pandemic. The number of cases worldwide is increasing exponentially and poses a major health threat, especially for those who are elderly, immuno-compromised, or have comorbidities. This also applies to AD patients on systemic immune-modulating treatment. In these days of uncertainty, reallocation of medical resources, curfew, hoarding, and shutdown of normal social life, patients, caregivers and doctors ask questions regarding the continuation of systemic immune-modulating treatment of AD patients. The ETFAD decided to address some of these questions here.

Background: Clinical registries may provide high-quality evidence on the use and effectiveness of therapeutic interventions under real-life conditions. Adults with moderate-to-severe atopic eczema (atopic dermatitis [AD]) are enrolled into TREATgermany and prospectively followed over at least 2years. This paper analyses the association between dermatological quality of life and work limitations.Materials and Methods: Treatment modalities and abroad set of physician- and patient-reported outcome measures are documented using validated instruments to assess clinical disease severity (EASI [Eczema Area and Severity Index], objective SCORAD [objective-SCORing Atopic Dermatitis]), quality of life (DLQI [Dermatology Life Quality Index]), symptoms (POEM [Patient-oriented Eczema Measure]), global disease severity, as well as patient satisfaction and work limitations including presenteeism (WLQ [Work Limitation Questionnaire]). From 06/2016 until 12/2017, 241 individuals (mean age 43 +/- 15years, 38.6% female) were enrolled at 19recruitment centers;69% of the patients were employed.Results: Employed persons had DLQI and WLQ scores of 10.6 +/- 6.9points and 17.7 +/- 18.1%, respectively. Mean presenteeism was substantial accounting for 9.2%. With coefficients of 0.39 and 0.33 WLQ and presenteeism scores significantly correlate with DLQI (p

Background In patients with subarachnoid hemorrhage (SAH), vasospasm remains one of the major complications. The application of intravenous magnesium sulfate (MgSO4) has been under discussion to prevent cerebral ischemia. Our aim was to examine the impact of early MgSO4 administration on local cerebral microcirculation during microsurgical clipping of SAH-related aneurysms. Methods The non-invasive laser-Doppler spectrophotometry system “Oxygen-to-See (O2C)” was used in 14 consecutive patients (11 female, 3 male, median age 56.5±9.7 yrs) with aneurysmatic SAH. A subdural probe measured capillary venous oxygenation (SO2), relative hemoglobin content (rHb), blood cell velocity (velo) and blood flow (flow) in 7 mm tissue depth. Data samples were recorded as baseline immediately before intraoperative application of MgSO4 10% 50 mg/kg body weight and 10 min thereafter. The continuous MgSO4 infusion rate depended on blood pressure (mean arterial pressure > 60-65 mmHg) and lasted a maximum of 60 min. Results MgSO4 was administered 2.8 (min. 1.6, max. 15.5) hours after onset of symptoms. Median flow increased significantly by 20.8% (5–68%, p = 0.001). Velo increased 4.9% (1–17%), rHb decreased 1.5% (3–34%) and SO2 decreased 9.4% (8–38%) by trend compared to the baseline values. FiO2 correlated positively with velo (rs = 0.712, p = 0.004), whereas arterial HCO3 correlated negatively with SO2 (rs = −0.599, p = 0.024). Of 14 patients, 2 had symptomatic vasospasm. Conclusions Our data suggest an increased cerebral blood flow after early intraoperative administration of MgSO4 in patients with SAH. Using a non-invasive laser-Doppler spectrophotometry system, this technique is feasible for continuous real-time monitoring of cerebral microcirculation. Trial registration DRKS (German Clinical Trial Registry), DRKS00013047 , retrospectively registered on September 21st, 2017.

Das atopische Ekzem ist eine typische multifaktorielle Erkrankung, bei der Umwelt- und Lebensstilfaktoren eine individuell vererbte Disposition in die Manifestation fuhren. Die Heritabilitat des atopischen Ekzems, d. h. der Anteil erblicher Faktoren an der Gesamtvarianz in der Bevolkerung, wird auf 70–80 % geschatzt. Die Moglichkeiten zur Entschlusselung erblicher Risikofaktoren haben sich in den letzten Jahren enorm erweitert. Als Folge konnten eine Vielzahl von Risikogenen identifiziert sowie erste Einblicke in Veranderungen des Epigenoms gewonnen werden. Mit dem wachsenden Verstandnis fur die konstitutionell bedingte Variabilitat entstehen zunehmend Krankheitsmodelle, die zeit- und entwicklungsabhangige Interaktionen zwischen genetischen und umweltbedingten Faktoren einbeziehen. Gleichzeitig rucken starker individualisierte Vorhersage-, Vorbeugungs- und Behandlungsansatze in greifbare Nahe.

SummaryAim The PETITE study (Sigurgeirsson et al.) aimed to compare safety and efficacy of pimecrolimus 1% cream (PIM) and low-to-medium-potency topical corticosteroids (TCS) in children with mild-to-moderate atopic dermatitis (AD). Setting and design Participants of this 5-year drug-company sponsored multicentre, open-label, parallel-group trial were recruited between April 2004 and October 2005. No details are reported regarding the study sites. Study exposure Infants aged ≥ 3 to < 12 months with mild-to-moderate AD were randomly assigned in a 1 : 1 ratio to receive either PIM or a low- or medium-potency TCS cream/ointment for 5 years. No information on specific TCS products used was provided. The topical treatment was applied twice daily ‘until complete AD clearance or for as long as allowed by the label of the specific TCS’, and was reinitiated at the occurrence of first signs and symptoms of AD flares. In the PIM group, exacerbations not controlled by PIM were treated with short-term TCSs. Outcomes Adverse events (AEs) and serious AEs (SAEs) were recorded ‘during clinic visits’. In a proportion of the patients, various immunological assessments including antibody titres to common vaccine antigens, immunoglobulin levels, B and T lymphocyte cell counts, and T-cell proliferation tests were performed. The children's growth was assessed by measuring height and weight. AD severity was measured using the Investigator Global Assessment (IGA) score and the percentage of the total body surface area affected. No specific information was provided on the number and scheduling of study visits. Primary outcomes were the incidence of AEs ‘of primary clinical interest’ and those with a crude incidence of ≥ 5% in either treatment group. Secondary outcome was ‘long-term efficacy’ defined as IGA ≤ 1 at week 3 and year 5. Results Patients in the PIM group experienced significantly more AEs [bronchitis (P = 0·02), infected eczema (P ≤ 0·001), impetigo (P = 0·045), nasopharyngitis (P = 0·04)]. No significant differences were seen for the other AEs. The overall incidence of SAEs was slightly higher for PIM (20·5% vs. 17·3%; P = 0·046). The proportion of participants with IGA ≤ 1 at year 5 was 88·7% for PIM and 92·3% for TCS, a success rate difference of 3·6% (95% confidence interval 0·8–6·4) favouring TCS. Conclusions Sigurgeirsson et al. conclude that the long-term management of mild-to-moderate AD in children with both TCS and PIM is safe, and that PIM has similar efficacy to TCS. Further, they conclude that their data support the use of PIM as a first-line treatment of mild-to-moderate AD in children.

Die beiden haufigsten chronisch-entzundlichen Dermatosen sind das atopische Ekzem mit einer Pravalenz von 15 % bei Kindern und 5 % bei Erwachsenen und die Psoriasis vulgaris mit einer Lebenszeitpravalenz von 3–5 %. Beide reprasentieren typische multifaktorielle Erkrankungen, deren Manifestation und Progression auf einem Zusammenspiel verschiedener genetischer sowie umweltbedingter Faktoren beruht. Die rasante technologische Entwicklung im Bereich der Molekulargenetik ermoglichte in den letzten Jahren tiefe Einblicke in die genetische Architektur dieser Erkrankungen. Insbesondere mithilfe genomweiter Assoziationsstudien ist es gelungen, eine eindrucksvolle Zahl genetischer Risikofaktoren zu identifizieren und so ein besseres Verstandnis der Pathophysiologie zu erreichen. Die Erkenntnisse aus der genetischen Epidemiologie werden zunehmend auch in klinische Fragestellungen ubersetzt, beispielsweise indem genetische Marker zur Stratifizierung von Patienten und betroffene biologische Prozesse zur Entwicklung neuer Behandlungsansatze genutzt werden. In der weiteren Erforschung der Zusammenhange zwischen genetischer Information und chronisch-entzundlichen Hautkrankheiten wird den neuen Sequenziertechniken und systembiologischen Ansatzen eine wichtige Rolle zukommen.

Eine empfindliche Haut geben vielen Personen in den entwickelten Landern an. Diese haben eine Veranlagung zu verschiedenen Hauterkrankungen, am haufigsten zu einer trockenen Haut, zur Atopie, zum seborrhoischen Ekzem, zur Acne vulgaris, zur Rosazea und zur perioralen Dermatitis und nennen Beschwerden durch Umweltfaktoren wie Kalte, Wind, Hitze, Sonnenexposition sowie Stress. Zudem werden verschiedene Hautpflegemittel und Kosmetika nicht vertragen. In der Pathophysiologie sind eine gestorte Barriere und eine reduzierte Stratum-corneum-Hydratation von groser Bedeutung. Aufgrund der gestorten Barriere konnen Umweltfaktoren und Hautpflegemittel die Haut leicht reizen. Von Bedeutung sind weiterhin neurogene Faktoren wie Stress und allgemeine Ubererregbarkeit. In der Signalubertragung spielen Zytokine und Neurotransmitter eine Rolle, wenngleich die Zusammenhange nur teilweise bekannt sind.

Eczema is often associated with development of allergic asthma. The Neuropeptide S Receptor 1 (NPSR1) gene has previously been associated with asthma and elevated serum IgE levels. The aim of this study was to investigate a potential association between the NPSR1 gene and eczema in patients and healthy individuals from five different populations in Western Europe, in total 6275 individuals. Seven single nucleotide polymorphisms previously associated with allergic asthma were genotyped. The protein expression of NPSR1 in the skin was studied using immunohistochemistry in six eczema patients and eight healthy individuals. No association was found be tween eczema and the seven single nucleotide polymor phisms in NPSR1 in any of the populations, either independently or in combinations. In addition, no difference was detected in epidermal NPSR1 expression between eczema patients and healthy individuals. These results strongly suggest that NPSR1 is not involved in the pathogenesis of eczema.

Background: Regulatory T cells (T-reg cells) have been described as an important cell population in the UV treatment of inflammatory skin diseases. Methods: We have treated five patients with generalized atopic eczema (AE) using medium-dose (15 cycles of 50 J/cm2, total dose of 750 J/cm2) UVA1 therapy and have analyzed the skin-infiltrating T-cellular subsets before and after therapy. Skin biopsies were split for immunohistochemistry and Real-time PCR and analyzed for CD4, Fox-P3, GATA-3, and IL-10 transcription as well as for CD3, CD4, CD152, Fox-P3, and GITR staining. Results: In all the investigated patients, we observed a good clinical response to UVA1. As described previously, the number of epidermal T cells slightly declined after irradiation. However, we did not observe a general decrease in T cell numbers. Within the population of T cells, no specific difference in the kinetics of Fox-P3-positive cells and Fox-P3-specific mRNA was noted as compared with GATA-3 positive T cells. These results were paralleled by RT-PCR for IL-10 and staining for CD152, a surface molecule that has been described for T-reg cells. Conclusion: In our hands, the clinical benefit of UVA1 treatment in AE patients does not seem to be due to a preferential survival/proliferation of T-reg cells.

There are remarkable differences in the diagnostic and therapeutic management of atopic dermatitis practiced by dermatologists and pediatricians in different countries. Therefore, the European Academy of Allergy and Clinical Immunology and the American Academy of Allergy, Asthma and Immunology nominated expert teams who were given the task of finding a consensus to serve as a guideline for clinical practice in Europe as well as in North America. The consensus report is part of the PRACTALL initiative, which is endorsed by both academies.

Summary Background The role of atopy in the pathophysiology of eczema is still under debate. The concept and analyses of the nonatopic and atopic subtypes of eczema have gained increasing interest in recent studies. The course of these subtypes and differences between boys and girls have not been investigated so far. Objectives To examine the course of nonatopic and atopic eczema in preschool children from Germany with regard to sex. Methods Repeated cross-sectional studies were performed in 5–7-year-old preschool children from Germany between 1994 and 2000. Individuals with eczema were identified by a dermatological examination. In addition to a questionnaire, skin prick tests and analyses of serum IgE antibodies against seven and five environmental allergens, respectively, were performed. Atopy was defined by sensitization to at least one of five common aeroallergens (birch, grass and mugwort pollen, house dust mites, cat dander). In part of the study population investigations of spare time behaviour and skin function were carried out (including stratum corneum hydration and skin surface pH). Results A total of 2693 girls and 2783 boys underwent a full dermatological examination of the skin and determination of sensitization. Among the girls, 8·7% demonstrated eczema clinically at the day of investigation in contrast to 6·1% of the boys. In girls, early onset eczema (

Background: Fresh frozen plasma (FFP) is exposed to numerous factors affecting the quality and stability of coagulation factors during blood collection, preparat

High brightness electron sources for linac based free-electron lasers (FELs) are being developed at the Photo Injector Test facility at DESY, Zeuthen site (PITZ). Production of electron bunches with extremely small transverse emittance is the focus of the PITZ scientific program. The photoinjector optimization in 2008–2009 for a bunch charge of 1, 0.5, 0.25, and 0.1 nC resulted in measured emittance values which are beyond the requirements of the European XFEL [S. Rimjaem et al., Nucl. Instrum. Methods Phys. Res., Sect. A 671, 62 (2012)NIMAER0168-900210.1016/j.nima.2011.12.101]. Several essential modifications were commissioned in 2010–2011 at PITZ, resulting in further improvement of the photoinjector performance. Significant improvement of the rf gun phase stability is a major contribution in the reduction of the measured transverse emittance. The old TESLA prototype booster was replaced by a new cut disk structure cavity. This allows acceleration of the electron beam to higher energies and supports much higher flexibility for stable booster operation as well as for longer rf pulses which is of vital importance especially for the emittance optimization of low charge bunches. The transverse phase space of the electron beam was optimized at PITZ for bunch charges in the range between 0.02 and 2 nC, where the quality of the beam measurements was preserved by utilizing long pulse train operation. The experimental optimization yielded worldwide unprecedented low normalized emittance beams in the whole charge range studied.

Background: In a recent genome wide scan, a functional promoter variant (rs2251746) in the gene encoding the alpha chain of the high affinity receptor for immunoglobulin E (IgE) (FCER1A) was identified as major determinant of serum IgE levels. Objective: The aim of this study was to investigate the role of rs2251746 on total IgE levels measured at different stages of life from birth (cord blood) up to the age of 6 and to evaluate its interaction with the environmental influences in two German birth cohorts. Method: Data from two German birth cohorts were analysed (n = 1043 for the LISA cohort and n = 1842 for the GINI cohort). In the studies, total serum IgE was measured from cord blood, and blood samples taken at the age of 2/3 and 6 years. In a subgroup of the LISA study, house dust samples were collected at age of 3 months and the amount of endotoxin was determined. Random effect models were used to analyse the longitudinal health outcomes. Results: In the two cohorts, the heterozygote and the rare homozygote of rs2251746 was consistently associated with lower total IgE levels from birth up to the age of 6 years with an allele-dose effect (P

Background Influences of microbial pathogens are crucial for the maturation of the immune system. Caspase-recruitment domain containing protein 15 (CARD 15) is a cytosolic receptor involved in bacterial recognition by antigen-presenting cells. CARD15 polymorphisms have been associated with Crohn's disease, Recently, associations with atopic phenotypes have been reported in children. Objective Within a large population of German adults (n = 1875), we evaluated eight CARD15 polymorphisms for associations with atopic phenotypes. Methods Subjects were phenotyped by standardized questionnaires and interviews as well as total and allergen-specific IgE measurements. Genotyping was performed using matrix-assisted laser desorption ionization - time of flight mass spectrometry. Haplotypes were estimated using the SAS/ Genetics module. Results Subjects with a T allele at rs1077861 had a decreased risk of developing asthma (odds ratio OR = 0.648, P = 0.013), whereas the presence of an A allele at rs3135500 was significantly associated with an increased risk (OR = 1.374, P = 0.023). In addition, a CARD15 haplotype revealed to be protective against the development of asthma (OR = 0.326, P = 0.003). Subjects with an A allele at position rs5743266 or a T allele at rs2066842 had a significantly decreased risk of developing allergic rhinoconjunctivitis with ORs of 0.820 (P = 0.049) and 0.801 (P = 0.025). Polymorphism rs2066845 showed a significant association with increased total serum IgE (OR = 2.155, P = 0.006). Conclusion Genetic variants of CARD15 that might result in inappropriate immunomodulation are not only associated with autoimmune diseases but also with atopic disorders.