Systematic update to the mammalian relative potency estimate database and development of best estimate toxic equivalency factors for dioxin-like compounds.

The World Health Organization (WHO) assesses potential health risks of dioxin-like compounds using Toxic Equivalency Factors (TEFs). This study systematically updated the relative potency (REP) database underlying the 2005 WHO TEFs and applied advanced methods for quantitative integration of study quality and dose-response. Data obtained from fifty-one publications more than doubled the size of the previous REP database (∼1300 datasets). REP quality and relevance for these data was assessed via application of a consensus-based weighting framework. Using Bayesian dose-response modeling, available data were modeled to produce standardized dose/concentration-response Hill curves. Study quality and REP data were synthesized via Bayesian meta-analysis to integrate dose/concentration-response data, author-calculated REPs and benchmark ratios. The output is a prediction of the most likely relationship between each congener and its reference as model-predicted TEF uncertainty distributions, or the 'best estimate TEF' (BE-TEF). The resulting weighted BE-TEFs were similar to the 2005 TEFs, though provide more information to inform selection of TEF values as well as to provide risk assessors and managers with information needed to quantitatively characterize uncertainty around TEF values. Collectively, these efforts produce an updated REP database and an objective, reproducible approach to support development of TEF values based on all available data.

High-precision comparison of the antiproton-to-proton charge-to-mass ratio.

Invariance under the charge, parity, time-reversal (CPT) transformation is one of the fundamental symmetries of the standard model of particle physics. This CPT invariance implies that the fundamental properties of antiparticles and their matter-conjugates are identical, apart from signs. There is a deep link between CPT invariance and Lorentz symmetry--that is, the laws of nature seem to be invariant under the symmetry transformation of spacetime--although it is model dependent. A number of high-precision CPT and Lorentz invariance tests--using a co-magnetometer, a torsion pendulum and a maser, among others--have been performed, but only a few direct high-precision CPT tests that compare the fundamental properties of matter and antimatter are available. Here we report high-precision cyclotron frequency comparisons of a single antiproton and a negatively charged hydrogen ion (H(-)) carried out in a Penning trap system. From 13,000 frequency measurements we compare the charge-to-mass ratio for the antiproton (q/m)p- to that for the proton (q/m)p and obtain (q/m)p-/(q/m)p − 1 =1(69) × 10(-12). The measurements were performed at cyclotron frequencies of 29.6 megahertz, so our result shows that the CPT theorem holds at the atto-electronvolt scale. Our precision of 69 parts per trillion exceeds the energy resolution of previous antiproton-to-proton mass comparisons as well as the respective figure of merit of the standard model extension by a factor of four. In addition, we give a limit on sidereal variations in the measured ratio of <720 parts per trillion. By following the arguments of ref. 11, our result can be interpreted as a stringent test of the weak equivalence principle of general relativity using baryonic antimatter, and it sets a new limit on the gravitational anomaly parameter of |α − 1| < 8.7 × 10(-7).

Thymic stromal lymphopoietin production induced by skin irritation results from concomitant activation of protease-activated receptor 2 and interleukin 1 pathways.

BACKGROUND: Thymic stromal lymphopoietin (TSLP) mediates proallergic T helper 2-type responses by acting on leucocytes. Endogenous pathways regulating TSLP production are poorly defined. OBJECTIVES: To uncover the mechanisms by which skin barrier disruption elicits TSLP production and to delineate the level at which individual mechanistic components may converge. METHODS: A combination of primary keratinocytes, skin explants and in vivo strategies was employed. Murine skin was tape stripped in the presence of neutralizing antibodies or antagonists. Cells and explants were stimulated with interleukin (IL)-1 and protease-activated receptor 2 agonist (PAR-2-Ag). TSLP levels were quantified by enzyme-linked immunosorbent assay and real-time quantitative polymerase chain reaction. Chromatin immunoprecipitation and promoter reporter assays were used to examine recruitment and functional activity of nuclear factor kappa B (NF-κB) at the TSLP promoter. RESULTS: TSLP induction in mouse skin occurred in a PAR-2- and IL-1-dependent manner. This scenario was duplicated by exogenous IL-1 plus PAR-2-Ag vs. each stimulus alone. Joint activity of PAR-2 and IL-1 was also observed in human keratinocytes. The TSLP promoter was identified as the target of PAR-2/IL-1, whereby PAR-2 activation augmented the recruitment of NF-κB and transcriptional activation over IL-1 alone. Combined treatment showed activity at concentrations of IL-1 unable to elicit NF-κB activity on their own. CONCLUSIONS: Skin barrier disruption activates the IL-1 and the PAR-2 pathways, which act in concert to activate the TSLP promoter and possibly other inflammatory genes. Awareness of this combined activity may permit a more flexible clinical management by selective targeting of either pathway individually or collectively. What's already known about this topic? Thymic stromal lymphopoietin (TSLP) is rapidly induced upon skin perturbation and mediates proallergic T helper 2-type responses by acting on leucocytes. Endogenous control of TSLP expression is poorly understood, but interleukin (IL)-1 is one regulator in the cutaneous environment In addition to IL-1, protease-activated receptor 2 (PAR-2) organizes central inflammatory pathways in the skin. What does this study add? IL-1 and PAR-2 pathways cooperate in driving TSLP production in mice and humans. Pathway integration occurs at the level of the TSLP promoter through enhanced recruitment and transcriptional activation of nuclear factor kappa B. When PAR-2 is co-stimulated, very low IL-1 levels (inactive by themselves) can induce biologically meaningful responses in the skin environment. What is the translational message? Physical skin irritation results in robust TSLP production by simultaneous activation of PAR-2 and IL-1 pathways.

Direct high-precision measurement of the magnetic moment of the proton.

One of the fundamental properties of the proton is its magnetic moment, µp. So far µp has been measured only indirectly, by analysing the spectrum of an atomic hydrogen maser in a magnetic field. Here we report the direct high-precision measurement of the magnetic moment of a single proton using the double Penning-trap technique. We drive proton-spin quantum jumps by a magnetic radio-frequency field in a Penning trap with a homogeneous magnetic field. The induced spin transitions are detected in a second trap with a strong superimposed magnetic inhomogeneity. This enables the measurement of the spin-flip probability as a function of the drive frequency. In each measurement the proton's cyclotron frequency is used to determine the magnetic field of the trap. From the normalized resonance curve, we extract the particle's magnetic moment in terms of the nuclear magneton: µp = 2.792847350(9)µN. This measurement outperforms previous Penning-trap measurements in terms of precision by a factor of about 760. It improves the precision of the forty-year-old indirect measurement, in which significant theoretical bound state corrections were required to obtain µp, by a factor of 3. By application of this method to the antiproton magnetic moment, the fractional precision of the recently reported value can be improved by a factor of at least 1,000. Combined with the present result, this will provide a stringent test of matter/antimatter symmetry with baryons.

[German Translation and Linguistic Validation of the Multidimensional Dyspnea Profile (MDP)]. / Deutsche Übersetzung und sprachliche Validierung des multidimensionalen Dyspnoe-Profils (MDP).

BACKGROUND: Dyspnea is characterized as a subjective perception of breathing discomfort. This includes distinct sensory qualities with distinct intensities. The detection and quantization of these quality distinctions can be quite difficult. As yet, there is no instrument in German covering the multidimensionality of dyspnea. Banzett et al. developed the Multidimensional Dyspnea Profile (MDP) in 2015 to meet and to understand the multidimensional nature of dyspnea, disease span and at varying times or situations. METHODS: This paper presents the German translation of the MDP. The MAPI Research Trust has developed the German version in accordance with the recognized guidelines for intercultural adaption of patient reported outcomes. That included a linguistic validation in patients with this condition. RESULTS: The Multidimensional Dyspnea Profile measures the intensity of dyspneic breathing discomforts. It tests five sensory qualities that describe the patient's dyspnea in its respective intensity. Additionally, it includes five potential reactions. The MDP is designed to refer to a specific event in time. CONCLUSION: The authors made the instrument freely available for academic use in English language. In addition, the German version is finally available and can be used in both everyday clinical practice and laboratory research.

Selective Targeting of High-Affinity LFA-1 Does Not Augment Costimulation Blockade in a Nonhuman Primate Renal Transplantation Model.

Costimulation blockade (CoB) via belatacept is a lower-morbidity alternative to calcineurin inhibitor (CNI)-based immunosuppression. However, it has higher rates of early acute rejection. These early rejections are mediated in part by memory T cells, which have reduced dependence on the pathway targeted by belatacept and increased adhesion molecule expression. One such molecule is leukocyte function antigen (LFA)-1. LFA-1 exists in two forms: a commonly expressed, low-affinity form and a transient, high-affinity form, expressed only during activation. We have shown that antibodies reactive with LFA-1 regardless of its configuration are effective in eliminating memory T cells but at the cost of impaired protective immunity. Here we test two novel agents, leukotoxin A and AL-579, each of which targets the high-affinity form of LFA-1, to determine whether this more precise targeting prevents belatacept-resistant rejection. Despite evidence of ex vivo and in vivo ligand-specific activity, neither agent when combined with belatacept proved superior to belatacept monotherapy. Leukotoxin A approached a ceiling of toxicity before efficacy, while AL-579 failed to significantly alter the peripheral immune response. These data, and prior studies, suggest that LFA-1 blockade may not be a suitable adjuvant agent for CoB-resistant rejection.

Ethnobotany, chemical constituents and biological activities of the flowers of Hydnora abyssinica A.Br. (Hydnoraceae).

Hydnora abyssinica A.Br. (Hydnoraceae), a holoparasitic herb, is for the first time recorded for Abyan governorate of South Yemen. Flowers of this species were studied for their ethnobotanical, biological and chemical properties for the first time. In South Yemen, they are traditionally used as wild food and to cure stomach diseases, gastric ulcer and cancer. Phytochemical analysis of the extracts showed the presence of terpenes, tannins, phenols, and flavonoids. The volatile components of the air-dried powdered flowers were identified using a static headspace GC/MS analysis as acetic acid, ethyl acetate, sabinene, α-terpinene, (+)-D-limonene and γ-terpinene. These volatile compounds that characterize the odor and taste of the flowers were detected for the first time in a species of the family Hydnoraceae. The flowers were extracted by n-hexane, dichlormethane, ethyl acetate, ethanol, methanol and water. With exception of the water extract all extracts demonstrated activities against Gram-positive bacteria as well as remarkable radical scavenging activities in DPPH assay. Ethyl acetate, methanol and water extracts exhibited good antifungal activities. The cytotoxic activity of the extracts against FL cells, measured in neutral red assay, was only weak (IC50 > 500 µg/mL). The results justify the traditional use of the flowers of Hydnora abyssinica in South Yemen.

[Prospective Evaluation of Risk Factors Concerning Intraoperative Conversion from Laparoscopic to Open Cholecystectomy]. / Prospektive Evaluation von Risikofaktoren bezüglich intraoperativer Konversion von laparoskopischer zu offener Cholezystektomie.

BACKGROUND: The surgical approach of choice in the treatment of symptomatic cholecystolithiasis is considered to be elective laparoscopic cholecystectomy (CCE) as the established gold standard. Today, approximately 80-90% of CCE are performed using a laparoscopic approach whereas the remaining portion undergoes primary conventional CCE, however, in 6% conversion is necessary. AIM: Since pathological aspects found intraoperatively and finally requiring conversion are correlated to an increased risk for complications, it appears reasonable to assess the risk factors prior to operation. PATIENTS AND METHODS: Through a well defined study period of 9 years, all consecutive patients who underwent CCE for cholecystolithiasis at the Municipal Hospital "HELIOS Klinikum Aue" were enrolled in a registry comparing laparoscopic and conversion CCE. Diverse parameters were tested as to whether they increase significantly the risk for conversion. The intensity of each factor-associated impact on a possible conversion was determined. RESULTS: From 2001 to 2009 1477 patients underwent CCE at the Municipal Hospital "Helios Klinikum Aue", out of them 131 (8.9%) cases were primarily treated by conventional CCE whereas in the vast majority (1346 subjects [91.1%]), laparoscopic CCE was the initial approach. However, conversion became necessary in 106 individuals resulting in a conversion rate of 7.9%. Comparing data obtained from laparoscopic CCE with those from open procedure after conversion, there were significant differences in operating time, complication rate and postoperative hospital stay (p = 0.01). Over the study period, there were 5 cases (0.37%) with iatrogenic injuries of the biliary system. Hospital mortality was 0.08% in the laparoscopic and 2.8% in the conversion group. The following parameters were found to have a significant impact on the risk for conversion (univariate analysis): elevation of CRP, preoperative ERCP, renal insufficiency, previous laparotomy, histological grade M3 (ulcerous, haemorrhagic necrotising cholecystitis, perforation of the gall bladder) and M4 (carcinoma of the gall bladder). While in the spectrum of preoperative factors former ERCP, elevation of CRP and terminal renal insufficiency were most relevant (2- to 3-fold each), histological grade M3 and M4, 7- and 14-fold, respectively, showed the greatest impact on conversion rate highlighting the profile of postoperative parameters. CONCLUSION: The main focus is directed to keep the conversion rate low. In case of diagnosing a severely inflamed gall bladder, a primarily open procedure or an early decision for conversion should be considered.

[Density equalizing mapping of obesity: analysis of a global epidemic]. / Density Equalizing Mapping der Adipositas: Analyse einer globalen Epidemie.

Obesity is a chronic disease whose origin is determined by genetic factors as well as environmental influences. The prevalence has rapidly increased worldwide in the recent decades. This paper evaluated the research on obesity in the period of 1900 - 2009 in the ISI "Web of Science" by Thomson Reuters. For this purpose scientometric methods were used and the results were graphically illustrated by "Density Equalizing Map Projections". From 1900 till 2009 94.987 published items are the basis for the present qualitative and quantitative data analysis. The publication rates show an exponential growth indicating a pronounced research activity. Concerning the country comparison the United States has the highest number of publications and citations, the highest modified h-index and most academic institutions. This manuscript shows the first comprehensive scientometric data on obesity. In this research area, the United States is a leader and is located at the center of global collaborations.

[Unilateral reduction of lung volume by application of intrabronchial valves on patients selected after endoscopic collateral ventilation assessment]. / Unilaterale Lungenvolumenreduktion mit intrabronchialen Ventilen nach Selektion mittels endoskopischer Kollateralventilationsmessung.

BACKGROUND: Endoscopic collateral ventilation assessment (ECVA) can be used to select patients suffering from emphysema for application of valves to achieve a reduction of lung volume. The objective is to obtain a post-operatively minimal clinically important improvement of the selected patient's physical capacity. METHODS: Patients with severe chronic obstructive pulmonary disease (COPD) underwent examination for a possible reduction of lung volume. Those selected got ECVA. Patients whose collateral resistance (Rcoll) increased to Rcoll > 10 cm H2O/(mL/s) within a measurement duration of up to 300 s, were submitted to unilateral lobar application of intrabronchial valves (IBV). Differences in residual volume (RV) as well as distances in 6 minute walk tests (6MWT) between the time after application of valves (TX) and that before (T1) were calculated (TX minus T1). RESULTS: Of a tested 310 emphysema patients, 17 met criteria allowing ECVA; 10 of 17 proved eligible for valve application. After 312 ±â€Š170 days (TX - T1) the increase in walking distance was 44 ±â€Š89.7 m; 7 of 10 patients achieved clinically relevant improvements (> 25 m). Differences in RV proved to correlate with differences in walking distances, but not yet with differences in measurement duration in ECVA. CONCLUSIONS: Only a small portion of patients with progressive emphysema of the lung seem suitable for endoscopic reduction of lung volume by application of valves. Unilateral lobar application of IBV can result in durable, clinically relevant improvements of the patient's physical capacity. ECVA measurements should take a minimum of 300 s.

Resolution of single spin flips of a single proton.

The spin magnetic moment of a single proton in a cryogenic Penning trap was coupled to the particle's axial motion with a superimposed magnetic bottle. Jumps in the oscillation frequency indicate spin flips and were identified using a Bayesian analysis.

Effects of inbreeding and temperature stress on life history and immune function in a butterfly.

Theory predicts that inbreeding depression should be more pronounced under environmental stress due to an increase in the expression of recessive deleterious alleles. If so, inbred populations may be especially vulnerable to environmental change. Against this background, we here investigate effects of inbreeding, temperature stress and its interactions with inbreeding in the tropical butterfly Bicyclus anynana. We use a full-factorial design with three levels of inbreeding (F = 0/0.25/0.38) and three temperature treatments (2 h exposure to 1, 27 or 39 °C). Despite using relatively low levels of inbreeding significant inbreeding depression was found in pupal mass, pupal time, thorax mass, abdomen fat content, egg hatching success and fecundity. However, stress resistance traits (heat tolerance, immune function) were not affected by inbreeding and interactions with temperature treatments were virtually absent. We thus found no support for an increased sensitivity of inbred individuals to environmental stress, and suspect that such patterns are restricted to harsher conditions. Our temperature treatments evidently imposed stress, significantly reducing longevity, fecundity, egg hatching success and haemocyte numbers, while fat content, protein content and lysozyme activity remained unaffected. Males and females differed in all traits measured except pupal time, protein content and phenoloxidase (PO) activity. Correlation analyses revealed, among others, a trade-off between PO and lysozyme activity, and negative correlations between fat content and several other traits. We stress that more data are needed on the effects of inbreeding, temperature variation and sexual differences on insect immune function before more general conclusions can be drawn.

[Telemonitoring of bike exercise training in patients with obstructive sleep apnoea]. / Telemonitoring von Fahrrad-Heimtraining bei Patienten mit obstruktiver Schlafapnoe.

BACKGROUND: Patients with obstructive sleep apnoea (OSA) suffer from daytime sleepiness, cognitive disorders and are at increased risk of cardiovascular diseases. In addition to continuous positive airway pressure (CPAP), major lifestyle changes to increase physical activity contribute to risk reduction. The daily training duration should be at least 20 minutes to achieve a relevant effect. In addition to exercise training in groups, home training is useful. However, sufficiently intensive training is often not performed because of unavailable feedback (monitoring). It is not clear yet how many patients accept a bicycle home training and to what extent they meet the specified training time. METHOD: Of the 152 consecutive OSA patients surveyed, 74 (48.7 %) agreed to a 4-week home exercise bike training. After exclusion of 51 patients, 17 for logistical reasons, and 34 because of severe comorbidities, 23 patients remained (age 51.0 +/- 9.3 years, BMI 33.7 +/- 4.2, ESS score 10.4 +/- 6.7, AHI 33.8 +/- 24.0). The daily duration of training at the ventilatory threshold (VT1) was recorded and transmitted by a wireless module (Cinterion) via Internet to a doctor or instructor. RESULTS: The patients exercised during 27.3 +/- 2.9 days. 19 of the 23 patients (83 %) accomplished the training period of > 20 minutes per day. In 4 patients (17 %) the training time was well below this target level with 5.9 +/- 2.3 min. The average training time of all patients was 24.4 +/- 9.0 min. CONCLUSION: About 50 % of the OSA patients are interested in a regular physical exercise bike training with telemonitoring, and are performing it quite constantly. The described method of telemonitoring provides a simple and, compared to group training cost-effective way to reduce cardiovascular risk in OSA.

Cryobiopsy increases the diagnostic yield of endobronchial biopsy: a multicentre trial.

Forceps, brushes or needles are currently the standard tools used during flexible bronchoscopy when diagnosing endobronchial malignancies. The new biopsy technique of cryobiopsy appears to provide better diagnostic samples. The aim of this study was to evaluate cryobiopsy over conventional endobronchial sampling. A total of 600 patients in eight centres with suspected endobronchial tumours were included in a prospective, randomised, single-blinded multicentre study. Patients were randomised to either sampling using forceps or the cryoprobe. After obtaining biopsy samples, a blinded histological evaluation was performed. According to the definitive clinical diagnosis, the diagnostic yield for malignancy was evaluated by a Chi-squared test. A total of 593 patients were randomised, of whom 563 had a final diagnosis of cancer. 281 patients were randomised to receive endobronchial biopsies using forceps and 282 had biopsies performed using a flexible cryoprobe. A definitive diagnosis was achieved in 85.1% of patients randomised to conventional forceps biopsy and 95.0% of patients who underwent cryobiopsy (p<0.001). Importantly, there was no difference in the incidence of significant bleeding. Endobronchial cryobiopsy is a safe technique with superior diagnostic yield in comparison with conventional forceps biopsy.

Gating the charge state of single molecules by local electric fields.

The electron-acceptor molecule TCNQ is found in either of two distinct integer charge states when embedded into a monolayer of a charge transfer complex on a gold surface. Scanning tunneling spectroscopy measurements identify these states through the presence or absence of a zero-bias Kondo resonance. Increasing the (tip-induced) electric field allows us to reversibly induce the oxidation or reduction of TCNQ species from their anionic or neutral ground state, respectively. We show that the different ground states arise from slight variations in the underlying surface potential, pictured here as the gate of a three-terminal device.

Ferromagnetic coupling of mononuclear Fe centers in a self-assembled metal-organic network on Au(111).

The magnetic state and magnetic coupling of individual atoms in nanoscale structures relies on a delicate balance between different interactions with the atomic-scale surroundings. Using scanning tunneling microscopy, we resolve the self-assembled formation of highly ordered bilayer structures of Fe atoms and organic linker molecules (T4PT) when deposited on a Au(111) surface. The Fe atoms are encaged in a three-dimensional coordination motif by three T4PT molecules in the surface plane and an additional T4PT unit on top. Within this crystal field, the Fe atoms retain a magnetic ground state with easy-axis anisotropy, as evidenced by x-ray absorption spectroscopy and x-ray magnetic circular dichroism. The magnetization curves reveal the existence of ferromagnetic coupling between the Fe centers.

Does selection on increased cold tolerance in the adult stage confer resistance throughout development?

Artificial selection is a powerful approach to unravel constraints on genetic adaptation. Although it has been frequently used to reveal genetic trade-offs among different fitness-related traits, only a few studies have targeted genetic correlations across developmental stages. Here, we test whether selection on increased cold tolerance in the adult stage increases cold resistance throughout ontogeny in the butterfly Bicyclus anynana. We used lines selected for decreased chill-coma recovery time and corresponding controls, which had originally been set up from three levels of inbreeding (outbred control, one or two full-sib matings). Four generations after having terminated selection, a response to selection was found in 1-day-old butterflies (the age at which selection took place). Older adults showed a very similar although weaker response. Nevertheless, cold resistance did not increase in either egg, larval or pupal stage in the selection lines but was even lower compared to control lines for eggs and young larvae. These findings suggest a cost of increased adult cold tolerance, presumably reducing resource availability for offspring provisioning and thereby stress tolerance during development, which may substantially affect evolutionary trajectories.

[Interdisciplinary AWMF guideline for the treatment of primary antibody deficiencies]. / Interdisziplinäre AWMF-Leitlinie zur Therapie primärer Antikörpermangelerkrankungen.

BACKGROUND: Currently, management of antibody deficient patients differs significantly among caregivers. Evidence and consensus based (S3) guidelines for the treatment of primary antibody deficiencies were developed to improve the management of these patients. METHODS: Based on a thorough analysis of current evidence (systematic literature search in PubMed; deadline November 2011) 14 recommendations were finalized during a consensus meeting in Frankfurt in November 2011 using structured consensus methods (nominal group technique). Experts were nominated by their scientific societies/patient initiatives (Tab. 1). RESULTS: The guidelines focus on indication, practical issues and monitoring of immunoglobulin replacement therapy as well as on different routes of administration. Furthermore recommendations regarding supportive measures such as antiinfective therapy, vaccinations and physiotherapy are given. Combining literature evidence and experience of caregivers within this evidence and consensus based guidelines offers the chance to improve the quality of care for anti-body deficient patients.

[Detection of daytime sleepiness using Epworth Sleepiness Scale and a 3-item questionnaire in obstructive sleep apnea]. / Erfassung der Tagesschläfrigkeit mittels Epworth-Schläfrigkeits-Skala und einem 3-Item-Fragebogen bei obstruktiver Schlafapnoe.

INTRODUCTION: The Epworth Sleepiness Scale (ESS) describes the likelihood of falling asleep in 8 specific situations. Pathological sleepiness (TS) of patients with obstructive sleep apnea (OSA) is most often diagnosed with an ESS score≥11 (TS-ESS). In an epidemiological study on the prevalence of sleep apnea syndrome (OSAS), only three questions with yes-no answers were used for the characterization of pathological daytime sleepiness (TS-Young): Due to the different construction of the ESS and the Young's questionnaire, we asked whether with the combination of the two questionnaires a larger number of patients with OSA and TS compared to the ESS can be identified. In addition, we examined the sleepiness questionnaires (FB) using objective vigilance in defined groups of OSA patients. METHODS: Using PSG 328 OSA patients with an AHI≥5 were identified. Vigilance was examined using the computer program CARDA. RESULTS: With both FB the same percentage of patients with AHI>5 with pathological sleepiness was found (48 %). By combining both FB (TS-comb), the number of patients increased from 158 (48.2 %) to 195 (59.5 %) significantly. The combination showed a significantly higher percentage with additional 37 (11.3 %) patients in comparison to the TS-ESS alone. Combining both FB, an increase of TS resulted in patients with below-average number of errors in the vigilance test (n=192) from 23.2 % to 31.4 % of these cases (p<0.001). CONCLUSIONS: As a single test both questionnaires can be used to detect daytime sleepiness with equal incidence. Combining both questionnaires a higher percentage of daytime sleepiness can be found in comparison to the ESS-questionnaire alone especially in patients without disturbance of vigilance.

[Interdisciplinary AWMF guideline for the diagnostics of primary immunodeficiency]. / Interdisziplinäre AWMF-Leitlinie zur Diagnostik von primären Immundefekten (S2k).

BACKGROUND: Primary immunodeficiencies are potentially life-threatening diseases. Over the last years, the clinical phenotype and the molecular basis of an increasing number of immunological defects have been characterized. However, in daily practice primary immunodeficiencies are still often diagnosed too late. Considering that an early diagnosis may reduce morbidity and mortality of affected patients, an interdisciplinary guideline for the diagnosis of primary immunodeficiencies was developed on behalf of the Arbeitsgemeinschaft Pädiatrische Immunologie (API) and the Deutsche Gesellschaft für Immunologie (DGfI). METHODS: The guideline is based on expert opinion and on knowledge from other guidelines and recommendations from Germany and other countries, supplemented by data from studies that support the postulated key messages (level of evidence III). With the contribution of 20 representatives, belonging to 14 different medical societies and associations, a consensus-based guideline with a representative group of developers and a structured consensus process was created (S2k). Under the moderation of a representative of the Association of the Scientific Medical Societies in Germany (AWMF) the nominal group process took place in April 2011. RESULTS: The postulated key messages were discussed and voted on following a structured consensus procedure. In particular, modified warning signs for primary immunodeficiencies were formulated and immunological emergency situations were defined.