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Institute
The genetic make-up of an individual contributes to the susceptibility and response to viral infection. Although environmental, clinical and social factors have a role in the chance of exposure to SARS-CoV-2 and the severity of COVID-191,2, host genetics may also be important. Identifying host-specific genetic factors may reveal biological mechanisms of therapeutic relevance and clarify causal relationships of modifiable environmental risk factors for SARS-CoV-2 infection and outcomes. We formed a global network of researchers to investigate the role of human genetics in SARS-CoV-2 infection and COVID-19 severity. Here we describe the results of three genome-wide association meta-analyses that consist of up to 49,562 patients with COVID-19 from 46 studies across 19 countries. We report 13 genome-wide significant loci that are associated with SARS-CoV-2 infection or severe manifestations of COVID-19. Several of these loci correspond to previously documented associations to lung or autoimmune and inflammatory diseases3,4,5,6,7. They also represent potentially actionable mechanisms in response to infection. Mendelian randomization analyses support a causal role for smoking and body-mass index for severe COVID-19 although not for type II diabetes. The identification of novel host genetic factors associated with COVID-19 was made possible by the community of human genetics researchers coming together to prioritize the sharing of data, results, resources and analytical frameworks. This working model of international collaboration underscores what is possible for future genetic discoveries in emerging pandemics, or indeed for any complex human disease.
We present measurements of exclusive ensuremathπ+,0 and η production in pp reactions at 1.25GeV and 2.2GeV beam kinetic energy in hadron and dielectron channels. In the case of π+ and π0 , high-statistics invariant-mass and angular distributions are obtained within the HADES acceptance as well as acceptance-corrected distributions, which are compared to a resonance model. The sensitivity of the data to the yield and production angular distribution of Δ (1232) and higher-lying baryon resonances is shown, and an improved parameterization is proposed. The extracted cross-sections are of special interest in the case of pp → pp η , since controversial data exist at 2.0GeV; we find \ensuremathσ=0.142±0.022 mb. Using the dielectron channels, the π0 and η Dalitz decay signals are reconstructed with yields fully consistent with the hadronic channels. The electron invariant masses and acceptance-corrected helicity angle distributions are found in good agreement with model predictions.
This study presents comprehensive real-world data on the use of anti-human epidermal growth factor receptor 2 (HER2) therapies in patients with HER2-positive metastatic breast cancer (MBC). Specifically, it describes therapy patterns with trastuzumab (H), pertuzumab + trastuzumab (PH), lapatinib (L), and trastuzumab emtansine (T-DM1). The PRAEGNANT study is a real-time, real-world registry for MBC patients. All therapy lines are documented. This analysis describes the utilization of anti-HER2 therapies as well as therapy sequences. Among 1936 patients in PRAEGNANT, 451 were HER2-positive (23.3%). In the analysis set (417 patients), 53% of whom were included in PRAEGNANT in the first-line setting, 241 were treated with H, 237 with PH, 85 with L, and 125 with T-DM1 during the course of their therapies. The sequence PH → T-DM1 was administered in 51 patients. Higher Eastern Cooperative Oncology Group (ECOG) scores, negative hormone receptor status, and visceral or brain metastases were associated with more frequent use of this therapy sequence. Most patients received T-DM1 after treatment with pertuzumab. Both novel therapies (PH and T-DM1) are utilized in a high proportion of HER2-positive breast cancer patients. As most patients receive T-DM1 after PH, real-world data may help to clarify whether the efficacy of this sequence is similar to that in the approval study.
Methodik
(2002)
Die vegetationskundliche und strukturelle Zuordnung der Lebensraumtypen erfolgt nach der vorrangig von Braun-Blanquet entwickelten Vegetationsklassifizierung, einer hierarchischen Gliederung der Vegetationstypen (Syntaxonomie), die die Ebenen der Assoziation, des Verbandes, der Ordnung und der Klasse umfasst. Hierbei ist die Assoziation die grundlegende Einheit, in der die Pflanzengesellschaften zusammengefasst werden, die sich durch gleiche charakteristische Arten(gruppen)kombinationen auszeichnen. Der Verband vereinigt ähnliche Assoziationen. Das sind bereits umfassendere, jedoch standörtlich noch recht einheitliche Vegetationseinheiten. In Ordnungen werden ähnliche Verbände zusammengefasst. Die Klasse vereinigt ähnliche Ordnungen.
The Transition Radiation Detector (TRD) was designed and built to enhance the capabilities of the ALICE detector at the Large Hadron Collider (LHC). While aimed at providing electron identification and triggering, the TRD also contributes significantly to the track reconstruction and calibration in the central barrel of ALICE. In this paper the design, construction, operation, and performance of this detector are discussed. A pion rejection factor of up to 410 is achieved at a momentum of 1 GeV/c in p–Pb collisions and the resolution at high transverse momentum improves by about 40% when including the TRD information in track reconstruction. The triggering capability is demonstrated both for jet, light nuclei, and electron selection.
The Transition Radiation Detector (TRD) was designed and built to enhance the capabilities of the ALICE detector at the Large Hadron Collider (LHC). While aimed at providing electron identification and triggering, the TRD also contributes significantly to the track reconstruction and calibration in the central barrel of ALICE. In this paper the design, construction, operation, and performance of this detector are discussed. A pion rejection factor of up to 410 is achieved at a momentum of 1 GeV/c in p-Pb collisions and the resolution at high transverse momentum improves by about 40% when including the TRD information in track reconstruction. The triggering capability is demonstrated both for jet, light nuclei, and electron selection.
The Transition Radiation Detector (TRD) was designed and built to enhance the capabilities of the ALICE detector at the Large Hadron Collider (LHC). While aimed at providing electron identification and triggering, the TRD also contributes significantly to the track reconstruction and calibration in the central barrel of ALICE. In this paper the design, construction, operation, and performance of this detector are discussed. A pion rejection factor of up to 410 is achieved at a momentum of 1 GeV/c in p-Pb collisions and the resolution at high transverse momentum improves by about 40% when including the TRD information in track reconstruction. The triggering capability is demonstrated both for jet, light nuclei, and electron selection.
We present the first wide-range measurement of the charged-particle pseudorapidity density distribution, for different centralities (the 0-5%, 5-10%, 10-20%, and 20-30% most central events) in Pb-Pb collisions at sNN−−−√=2.76 TeV at the LHC. The measurement is performed using the full coverage of the ALICE detectors, −5.0<η<5.5, and employing a special analysis technique based on collisions arising from LHC "satellite" bunches. We present the pseudorapidity density as a function of the number of participating nucleons as well as an extrapolation to the total number of produced charged particles (Nch=17165±772 for the 0-5% most central collisions). From the measured dNch/dη distribution we derive the rapidity density distribution, dNch/dy, under simple assumptions. The rapidity density distribution is found to be significantly wider than the predictions of the Landau model. We assess the validity of longitudinal scaling by comparing to lower energy results from RHIC. Finally the mechanisms of the underlying particle production are discussed based on a comparison with various theoretical models.
We report on the first measurement of inclusive J/ψ elliptic flow, v2, in heavy-ion collisions at the LHC. The measurement is performed with the ALICE detector in Pb-Pb collisions at sNN−−−√=2.76 TeV in the rapidity range 2.5<y<4.0. The dependence of the J/ψ v2 on the collision centrality and on the J/ψ transverse momentum is studied in the range 0<pT<10 GeV/c. For semi-central Pb-Pb collisions at sNN−−−√=2.76 TeV, an indication of non-zero v2 is observed with a maximum value of v2=0.116±0.046(stat.)±0.029(syst.) for J/ψ in the transverse momentum range 2<pT<4 GeV/c. The elliptic flow measurement complements the previously reported ALICE results on the inclusive J/ψ nuclear modification factor and favors the scenario of a significant fraction of J/ψ production from charm quarks in a deconfined partonic phase.
Observation of enhanced subthreshold K+ production in central collisions between heavy nuclei
(1994)
In the very heavy collision system 197Au+197Au the K+ production process was studied as a function of impact parameter at 1 GeV/nucleon, a beam energy well below the free N-N threshold. The K+ multiplicity increases more than linearly with the number of participant nucleons and the K+/ pi + ratio rises significantly when going from peripheral to central collisions. The measured K+ double differential cross section is enhanced by a factor of 6 compared to microscopic transport calculations if secondary processes (Delta N-->K Lambda N and Delta Delta -->K Lambda N) are ignored.
In this letter we report the first multi-differential measurement of correlated pion-proton pairs from 2 billion Au+Au collisions at sNN=2.42 GeV collected with HADES. In this energy regime the population of Δ(1232) resonances plays an important role in the way energy is distributed between intrinsic excitation energy and kinetic energy of the hadrons in the fireball. The triple differential d3N/dMπ±pdpTdy distributions of correlated π±p pairs have been determined by subtracting the πp combinatorial background using an iterative method. The invariant-mass distributions in the Δ(1232) mass region show strong deviations from a Breit-Wigner function with vacuum width and mass. The yield of correlated pion-proton pairs exhibits a complex isospin, rapidity and transverse-momentum dependence. In the invariant mass range 1.1<Minv(GeV/c2)<1.4, the yield is found to be similar for π+p and π−p pairs, and to follow a power law 〈Apart〉α, where 〈Apart〉 is the mean number of participating nucleons. The exponent α depends strongly on the pair transverse momentum (pT) while its pT-integrated and charge-averaged value is α=1.5±0.08st±0.2sy.
We present the results of two-pion production in tagged quasi-free np collisions at a deutron incident beam energy of 1.25 GeV/c measured with the High-Acceptance Di-Electron Spectrometer (HADES) installed at GSI. The specific acceptance of HADES allowed for the first time to obtain high-precision data on π+π− and π−π0 production in np collisions in a region corresponding to large transverse momenta of the secondary particles. The obtained differential cross section data provide strong constraints on the production mechanisms and on the various baryon resonance contributions (∆∆, N(1440), N(1520), ∆(1600)). The invariant mass and angular distributions from the np → npπ+π −and np → ppπ−π0 reactions are compared with different theoretical model predictions.
We present first data on sub-threshold production of Ks0 mesons and Λ hyperons in Au+Au collisions at sNN=2.4 GeV. We observe an universal 〈Apart〉 scaling of hadrons containing strangeness, independent of their corresponding production thresholds. Comparing the yields, their 〈Apart〉 scaling, and the shapes of the rapidity and the pt spectra to state-of-the-art transport model (UrQMD, HSD, IQMD) predictions, we find that none of them can simultaneously describe these observables with reasonable χ2 values.
We investigate identical pion HBT intensity interferometry in central Au+Au collisions at 1.23A GeV. High-statistics π−π− and π+π+ data are measured with HADES at SIS18/GSI. The radius parameters, derived from the correlation function depending on relative momenta in the longitudinally comoving system and parametrized as three-dimensional Gaussian distribution, are studied as function of transverse momentum. A substantial charge-sign difference of the source radii is found, particularly pronounced at low transverse momentum. The extracted source parameters agree well with a smooth extrapolation of the center-of-mass energy dependence established at higher energies, extending the corresponding excitation functions down towards a very low energy.
Standard values of the upper body posture in healthy adults with special regard to age, sex and BMI
(2023)
In order to classify and analyze the parameters of upper body posture in clinical or physiotherapeutic settings, a baseline in the form of standard values with special regard to age, sex and BMI is required. Thus, subjectively healthy men and women aged 21–60 years were measured in this project. The postural parameters of 800 symptom-free male (n = 397) and female (n = 407) volunteers aged 21–60 years (Ø♀: 39.7 ± 11.6, Ø ♂: 40.7 ± 11.5 y) were studied. The mean height of the men was 1.8 ± 0.07 m, with a mean body weight of 84.8 ± 13.1 kg and an average BMI of 26.0 ± 3.534 kg/m2. In contrast, the mean height of the women was 1.67 ± 0.06 m, with a mean body weight of 66.5 ± 12.7 kg and an average BMI of 23.9 ± 4.6 kg/m2. By means of video rasterstereography, a 3-dimensional scan of the upper back surface was measured when in a habitual standing position. The means or medians, confidence intervals, tolerance ranges, the minimum, 2.5, 25, 50, 75, 97.5 percentiles and the maximum, plus the kurtosis and skewness of the distribution, were calculated for all parameters. Additionally, ANOVA and a factor analyses (sex, BMI, age) were conducted. In both sexes across all age groups, balanced, symmetrical upper body statics were evident. Most strikingly, the females showed greater thoracic kyphosis and lumbar lordosis angles (kyphosis: Ø ♀ 56°, Ø♂ 51°; lordosis: Ø ♀ 49°, Ø♂ 32°) and lumbar bending angles (Ø ♀ 14°, Ø♂ 11°) than the males. The distance between the scapulae was more pronounced in men. These parameters also show an increase with age and BMI, respectively. Pelvic parameters were independent of age and sex. The upper body postures of women and men between the ages of 21 and 60 years were found to be almost symmetrical and axis-conforming with a positive correlation for BMI or age. Consequently, the present body posture parameters allow for comparisons with other studies, as well as for the evaluation of clinical (interim) diagnostics and applications.
In March 2019 the HADES experiment recorded 14 billion Ag+Ag collisions at √sNN = 2.55 GeV as a part of the FAIR phase-0 physics program. In this contribution, we present and investigate our capabilities to reconstruct and analyze weakly decaying strange hadrons and hypernuclei emerging from these collisions. The focus is put on measuring the mean lifetimes of these particles.
Many QCD based and phenomenological models predict changes of hadron properties in a strongly interacting environment. The results of these models differ significantly and the experimental determination of hadron properties in nuclear matter is essential. In this paper we present a review of selected physics results obtained at GSI Helmholtzzentrum für Schwerionenforschung GmbH by HADES (High-Acceptance Di-Electron Spectrometer). The e+e− pair emission measured for proton and heavy-ion induced collisions is reported together with results on strangeness production. The future HADES activities at the planned FAIR facility are also discussed.
The High Acceptance DiElectron Spectrometer HADES [1] is installed at the Helmholtzzentrum für Schwerionenforschung (GSI) accelerator facility in Darmstadt. It investigates dielectron emission and strangeness production in the 1-3 AGeV regime. A recent experiment series focusses on medium-modifications of light vector mesons in cold nuclear matter. In two runs, p+p and p+Nb reactions were investigated at 3.5 GeV beam energy; about 9·109 events have been registered. In contrast to other experiments the high acceptance of the HADES allows for a detailed analysis of electron pairs with low momenta relative to nuclear matter, where modifications of the spectral functions of vector mesons are predicted to be most prominent. Comparing these low momentum electron pairs to the reference measurement in the elementary p+p reaction, we find in fact a strong modification of the spectral distribution in the whole vector meson region.
New results on the differential cross section in deuteron-proton elastic scattering are obtained at the deuteron kinetic energy of 2.5 GeV with the HADES spectrometer. The angular range of 69° – 125° in the center of mass system is covered. The obtained results are compared with the relativistic multiple scattering model calculation using the CD-Bonn deuteron wave function. The data at fixed scattering angles in the c.m. are in qualitative agreement with the constituent counting rules prediction.
n this paper we report on the investigation of baryonic resonance production in proton-proton collisions at the kinetic energies of 1.25 GeV and 3.5 GeV, based on data measured with HADES. Exclusive channels npπ+ and ppπ0 as well as ppe+e− were studied simultaneously in the framework of a one-boson exchange model. The resonance cross sections were determined from the one-pion channels for Δ(1232) and N(1440) (1.25 GeV) as well as further Δ and N* resonances up to 2 GeV/c2 for the 3.5 GeV data. The data at 1.25 GeV energy were also analysed within the framework of the partial wave analysis together with the set of several other measurements at lower energies. The obtained solutions provided the evolution of resonance production with the beam energy, showing a sizeable non-resonant contribution but with still dominating contribution of Δ(1232)P33. In the case of 3.5 GeV data, the study of the ppe+e− channel gave the insight on the Dalitz decays of the baryon resonances and, in particular, on the electromagnetic transition form-factors in the time-like region. We show that the assumption of a constant electromagnetic transition form-factors leads to underestimation of the yield in the dielectron invariant mass spectrum below the vector mesons pole. On the other hand, a comparison with various transport models shows the important role of intermediate ρ production, though with a large model dependency. The exclusive channels analysis done by the HADES collaboration provides new stringent restrictions on the parameterizations used in the models.
We present data on charged kaons (K±) and ϕ mesons in Au(1.23A GeV)+Au collisions. It is the first simultaneous measurement of K− and ϕ mesons in central heavy-ion collisions below a kinetic beam energy of 10A GeV. The ϕ/K− multiplicity ratio is found to be surprisingly high with a value of 0.52±0.16 and shows no dependence on the centrality of the collision. Consequently, the different slopes of the K+ and K− transverse-mass spectra can be explained solely by feed-down, which substantially softens the spectra of K− mesons. Hence, in contrast to the commonly adapted argumentation in literature, the different slopes do not necessarily imply diverging freeze-out temperatures of K+ and K− mesons caused by different couplings to baryons.
The knowledge of baryonic resonance properties and production cross sections plays an important role for the extraction and understanding of medium modifications of mesons in hot and/or dense nuclear matter. We present and discuss systematics on dielectron and strangeness production obtained with HADES on p+p, p+A and A+A collisions in the few GeV energy regime with respect to these resonances.
his contribution aims to give a basic overview of the latest results regarding the production of resonances in different collision systems. The results were extracted from experimental data collected with HADES that is a multipurpose detector located at the GSI Helmholtzzentrum, Darmstadt. The main points discussed here are: the properties of the strange resonances Λ(1405) and Σ(1385), the role of Δ’s as a source of pions in the final state, the production dynamics reflected in form of differential cross sections, and the role of the ϕ meson as a source for K− particles.
Radiative transition of an excited baryon to a nucleon with emission of a virtual massive photon converting to dielectron pair (Dalitz decays) provides important information about baryon-photon coupling at low q2 in timelike region. A prominent enhancement in the respective electromagnetic transition Form Factors (etFF) at q2 near vector mesons ρ/ω poles has been predicted by various calculations reflecting strong baryon-vector meson couplings. The understanding of these couplings is also of primary importance for the interpretation of the emissivity of QCD matter studied in heavy ion collisions via dilepton emission. Dedicated measurements of baryon Dalitz decays in proton-proton and pion-proton scattering with HADES detector at GSI/FAIR are presented and discussed. The relevance of these studies for the interpretation of results obtained from heavy ion reactions is elucidated on the example of the HADES results.
Mutations of the isocitrate dehydrogenase-1 (IDH1) and IDH2 genes are among the most frequent alterations in acute myeloid leukemia (AML) and can be found in ∼20% of patients at diagnosis. Among 4930 patients (median age, 56 years; interquartile range, 45-66) with newly diagnosed, intensively treated AML, we identified IDH1 mutations in 423 (8.6%) and IDH2 mutations in 575 (11.7%). Overall, there were no differences in response rates or survival for patients with mutations in IDH1 or IDH2 compared with patients without mutated IDH1/2. However, distinct clinical and comutational phenotypes of the most common subtypes of IDH1/2 mutations could be associated with differences in outcome. IDH1-R132C was associated with increased age, lower white blood cell (WBC) count, less frequent comutation of NPM1 and FLT3 internal tandem mutation (ITD) as well as with lower rate of complete remission and a trend toward reduced overall survival (OS) compared with other IDH1 mutation variants and wild-type (WT) IDH1/2. In our analysis, IDH2-R172K was associated with significantly lower WBC count, more karyotype abnormalities, and less frequent comutations of NPM1 and/or FLT3-ITD. Among patients within the European LeukemiaNet 2017 intermediate- and adverse-risk groups, relapse-free survival and OS were significantly better for those with IDH2-R172K compared with WT IDH, providing evidence that AML with IDH2-R172K could be a distinct entity with a specific comutation pattern and favorable outcome. In summary, the presented data from a large cohort of patients with IDH1/2 mutated AML indicate novel and clinically relevant findings for the most common IDH mutation subtypes.
Proteins encoded by small open reading frames (sORFs) have a widespread occurrence in diverse microorganisms and can be of high functional importance. However, due to annotation biases and their technically challenging direct detection, these small proteins have been overlooked for a long time and were only recently rediscovered. The currently rapidly growing number of such proteins requires efficient methods to investigate their structure–function relationship. Herein, a method is presented for fast determination of the conformational properties of small proteins. Their small size makes them perfectly amenable for solution-state NMR spectroscopy. NMR spectroscopy can provide detailed information about their conformational states (folded, partially folded, and unstructured). In the context of the priority program on small proteins funded by the German research foundation (SPP2002), 27 small proteins from 9 different bacterial and archaeal organisms have been investigated. It is found that most of these small proteins are unstructured or partially folded. Bioinformatics tools predict that some of these unstructured proteins can potentially fold upon complex formation. A protocol for fast NMR spectroscopy structure elucidation is described for the small proteins that adopt a persistently folded structure by implementation of new NMR technologies, including automated resonance assignment and nonuniform sampling in combination with targeted acquisition.
Aim: To assess outcomes in patients with advanced adenocarcinoma non-small-cell lung cancer who received nintedanib plus docetaxel after progression on prior chemotherapy followed by immune checkpoint inhibitor (ICI) therapy. Patients & methods: VARGADO is a prospective, noninterventional study. We describe initial data from a cohort of 22 patients who received nintedanib plus docetaxel after chemotherapy and ICI therapy. Results: Median progression-free survival with nintedanib plus docetaxel was 5.5 months (95% CI: 1.9–8.7 months). The objective response rate was 7/12 (58%) and the disease control rate was 10/12 (83%). Data for overall survival rate 12 months after the start of treatment (primary end point) are not yet mature and are not reported. Of 22 patients, 73% experienced drug-related adverse events; adverse events led to treatment discontinuation in 32% of patients. Conclusion: These data highlight the potential clinical benefit of nintedanib plus docetaxel in patients who failed prior ICI therapy.
Trial registration number: NCT02392455
Unique features of a global human ectoparasite identified through sequencing of the bed bug genome
(2016)
The bed bug, Cimex lectularius, has re-established itself as a ubiquitous human ectoparasite throughout much of the world during the past two decades. This global resurgence is likely linked to increased international travel and commerce in addition to widespread insecticide resistance. Analyses of the C. lectularius sequenced genome (650 Mb) and 14,220 predicted protein-coding genes provide a comprehensive representation of genes that are linked to traumatic insemination, a reduced chemosensory repertoire of genes related to obligate hematophagy, host–symbiont interactions, and several mechanisms of insecticide resistance. In addition, we document the presence of multiple putative lateral gene transfer events. Genome sequencing and annotation establish a solid foundation for future research on mechanisms of insecticide resistance, human–bed bug and symbiont–bed bug associations, and unique features of bed bug biology that contribute to the unprecedented success of C. lectularius as a human ectoparasite.
Objectives: Symmetrical dental occlusion blocking is used in dentistry as a quick diagnostic tool to test for potential influences of the craniomandibular system on body sway and weight distribution. This study presents the changes of body sway and pressure distribution in healthy subjects, free of a temporomandibular dysfunction (TMD). Immediate effects between occlusal blocking and rest position on body sway and body weight distribution in general, as well as for both genders and for four age decades will be evaluated.
Materials and methods: 725 (396f/329 m) subjects (neither subjective signs of TMD nor acute/chronic complaints in the musculoskeletal system) volunteered (21 to 60 years) while both genders were divided into four age groups according to decades. A pressure measuring platform was used. Body sway and weight distribution were recorded in two dental occlusion conditions (a) in rest position and (b) symmetrical blocking (bicuspid region) by cotton rolls.
Results: Both, the frontal sway and the sagittal sway reduced by 0.67 mm (t(724) = − 3.9 (p < 0.001)) and by 0.33 mm (t(724) = − 3.4 (p < 0.001)). The relative pressure under the left forefoot increased by 0.33% (t(724) = 2.88 (p < 0.001)) and the relative pressure overall under the forefoot increased by 0.67% (t(724) = − 3.4 (p < 0.001)). Gender-specific, age-specific and BMI-specific reactions could not be identified.
Conclusions: Subjects, free of any TMD and with no complaints of the musculoskeletal system, show small changes of the body sway and weight distribution when biting symmetrically on a cotton roll. These changes are independent of age, gender or body mass index (BMI). Due to the relative large sample size, the presented results can also be seen as norm values when body sway is used as an additional assessment of a TMD.
INTRODUCTION: Older patients with acute myeloid leukemia (AML) experience short survival despite intensive chemotherapy. Azacitidine has promising activity in patients with low proliferating AML. The aim of this dose-finding part of this trial was to evaluate feasibility and safety of azacitidine combined with a cytarabine- and daunorubicin-based chemotherapy in older patients with AML.
TRIAL DESIGN: Prospective, randomised, open, phase II trial with parallel group design and fixed sample size.
PATIENTS AND METHODS: Patients aged 61 years or older, with untreated acute myeloid leukemia with a leukocyte count of <20,000/µl at the time of study entry and adequate organ function were eligible. Patients were randomised to receive azacitidine either 37.5 (dose level 1) or 75 mg/sqm (dose level 2) for five days before each cycle of induction (7+3 cytarabine plus daunorubicine) and consolidation (intermediate-dose cytarabine) therapy. Dose-limiting toxicity was the primary endpoint.
RESULTS: Six patients each were randomised into each dose level and evaluable for analysis. No dose-limiting toxicity occurred in either dose level. Nine serious adverse events occurred in five patients (three in the 37.5 mg, two in the 75 mg arm) with two fatal outcomes. Two patients at the 37.5 mg/sqm dose level and four patients at the 75 mg/sqm level achieved a complete remission after induction therapy. Median overall survival was 266 days and median event-free survival 215 days after a median follow up of 616 days.
CONCLUSIONS: The combination of azacitidine 75 mg/sqm with standard induction therapy is feasible in older patients with AML and was selected as an investigational arm in the randomised controlled part of this phase-II study, which is currently halted due to an increased cardiac toxicity observed in the experimental arm.
Men and women differ substantially regarding height, weight, and body fat. Interestingly, previous work detecting genetic effects for waist-to-hip ratio, to assess body fat distribution, has found that many of these showed sex-differences. However, systematic searches for sex-differences in genetic effects have not yet been conducted. Therefore, we undertook a genome-wide search for sexually dimorphic genetic effects for anthropometric traits including 133,723 individuals in a large meta-analysis and followed promising variants in further 137,052 individuals, including a total of 94 studies. We identified seven loci with significant sex-difference including four previously established (near GRB14/COBLL1, LYPLAL1/SLC30A10, VEGFA, ADAMTS9) and three novel anthropometric trait loci (near MAP3K1, HSD17B4, PPARG), all of which were significant in women, but not in men. Of interest is that sex-difference was only observed for waist phenotypes, but not for height or body-mass-index. We found no evidence for sex-differences with opposite effect direction for men and women. The PPARG locus is of specific interest due to its link to diabetes genetics and therapy. Our findings demonstrate the importance of investigating sex differences, which may lead to a better understanding of disease mechanisms with a potential relevance to treatment options.
Background: Panic disorder is common (5% prevalence) and females are twice as likely to be affected as males. The heritable component of panic disorder is estimated at 48%. Glutamic acid dehydrogenase GAD1, the key enzyme for the synthesis of the inhibitory and anxiolytic neurotransmitter GABA, is supposed to influence various mental disorders, including mood and anxiety disorders. In a recent association study in depression, which is highly comorbid with panic disorder, GAD1 risk allele associations were restricted to females.
Methodology/Principal Findings: Nineteen single nucleotide polymorphisms (SNPs) tagging the common variation in GAD1 were genotyped in two independent gender and age matched case-control samples (discovery sample n = 478; replication sample n = 584). Thirteen SNPs passed quality control and were examined for gender-specific enrichment of risk alleles associated with panic disorder by using logistic regression including a genotype×gender interaction term. The latter was found to be nominally significant for four SNPs (rs1978340, rs3762555, rs3749034, rs2241165) in the discovery sample; of note, the respective minor/risk alleles were associated with panic disorder only in females. These findings were not confirmed in the replication sample; however, the genotype×gender interaction of rs3749034 remained significant in the combined sample. Furthermore, this polymorphism showed a nominally significant association with the Agoraphobic Cognitions Questionnaire sum score.
Conclusions/Significance: The present study represents the first systematic evaluation of gender-specific enrichment of risk alleles of the common SNP variation in the panic disorder candidate gene GAD1. Our tentative results provide a possible explanation for the higher susceptibility of females to panic disorder.
Simple Summary: Renal insufficiency is frequently seen in newly diagnosed multiple myeloma and can be due to the disease itself but also caused by medical interventions or infections. Patients with severe renal insufficiency are known to have an adverse prognosis, but recently, it was shown that even moderately impaired kidney function can have long-term sequelae. Achieving quick disease control by effective antimyeloma therapy can lead to the recovery of renal function. We investigated the kidney-specific variables in a large cohort of 770 myeloma patients receiving three different three-drug regimens for initial myeloma treatment to learn more about the differential effects on kidney function in an early disease phase. All regimens had a positive impact on kidney function without a difference in the proportion of patients who reached normal renal function after three cycles. Interestingly, patients who received bortezomib, lenalidomide, and dexamethasone tended to have higher risk for a worse renal function following induction when compared to the initial values.
Abstract: Background: Preservation of kidney function in newly diagnosed (ND) multiple myeloma (MM) helps to prevent excess toxicity. Patients (pts) from two prospective trials were analyzed, provided postinduction (PInd) restaging was performed. Pts received three cycles with bortezomib (btz), cyclophosphamide, and dexamethasone (dex; VCD) or btz, lenalidomide (len), and dex (VRd) or len, adriamycin, and dex (RAD). The minimum required estimated glomerular filtration rate (eGFR) was >30 mL/min. We analyzed the percent change of the renal function using the International Myeloma Working Group (IMWG) criteria and Kidney Disease: Improving Global Outcomes (KDIGO)-defined categories. Results: Seven hundred and seventy-two patients were eligible. Three hundred and fifty-six received VCD, 214 VRd, and 202 RAD. VCD patients had the best baseline eGFR. The proportion of pts with eGFR <45 mL/min decreased from 7.3% at baseline to 1.9% PInd (p < 0.0001). Thirty-seven point one percent of VCD versus 49% of VRd patients had a decrease of GFR (p = 0.0872). IMWG-defined “renal complete response (CRrenal)” was achieved in 17/25 (68%) pts after VCD, 12/19 (63%) after RAD, and 14/27 (52%) after VRd (p = 0.4747). Conclusions: Analyzing a large and representative newly diagnosed myeloma (NDMM) group, we found no difference in CRrenal that occurred independently from the myeloma response across the three regimens. A trend towards deterioration of the renal function with VRd versus VCD may be explained by a better pretreatment “renal fitness” in the latter group.
Comparative values are essential for the classification of orthopedic abnormalities and the assessment of a necessary therapy. At present, reference values for the upper body posture for healthy, male adults exist for the age groups of 18–35, 31–40 and 41–50 years. However, corresponding data on the decade of 51 to 60 year-old healthy men are still lacking. 23 parameters of the upper body posture were analyzed in 102 healthy male participants aged 51–60 (55.36 ± 2.78) years. The average height was 180.76 ± 7.81 cm with a weight of 88.22 ± 14.57 kg. The calculated BMI was 26.96 ± 3.92 kg/m2. In the habitual, upright position, the bare upper body was scanned three-dimensionally using video raster stereography. Mean or median values, confidence intervals, tolerance ranges and group comparisons, as well as correlations of BMI and physical activity, were calculated for all parameters. The spinal column parameters exhibited a good exploration of the frontal plane in the habitual standing position. In the sagittal plane, a slight, ventral inclination of the trunk with an increased kyphosis angle of the thoracic spine and increased thoracic bending angle was observed. The parameters of the pelvis showed a pronounced symmetry with deviations from the 0° axis within the measurement error margin of 1 mm/1°. The scapula height together with the scapula angles of the right and left side described a slightly elevated position of the left shoulder compared to the right side. The upper body posture is influenced by parameters of age, height, weight and BMI. Primarily there are significant correlations to measurements of trunk lengths D (age: p ≤ 0.02, rho = -0.23; height: p ≤ 0.001, rho = 0.58; weight: p ≤ 0.001, rho = 0.33), trunk lengths S (age: p ≤ 0.01, rho = -0.27; height: p ≤ 0.001, rho = 0.58; weight: p ≤ 0.001, rho = 0.32), pelvic distance (height: p ≤ 0.01, rho = 0.26; weight: p ≤ 0.001, rho = 0.32; BMI: p ≤ 0.03, rho = 0.22) and scapula distance (weight: p ≤ 0.001, rho = .32; BMI: p ≤ 0.01, rho = 0.27), but also to sagittal parameters of trunk decline (weight: p ≤ 0.001, rho = -0.29; BMI: p ≤ 0.01, rho = -0.24), thoracic bending angle (height: p ≤ 0.01, rho = 0.27) and kyphosis angle (BMI: p ≤ 0.03, rho = 0.21). The upper body posture of healthy men between the ages of 51 and 60 years was axially almost aligned and balanced. With the findings of this investigation and the reference values obtained, suitable comparative values for use in clinical practice and for further scientific studies with the same experimental set-up have been established.
Background: Temporary occlusal changes and their influence on the upper body statics are still controversially discussed. Furthermore, concrete statements on whether age- or gender-specific differences in neurophysiological reactions exist are missing. Therefore, it is the aim of this study to evaluate the immediate effects of a symmetrical occlusion blocking on the upper body posture. These effects shall be investigated for both genders and for a larger age range.
Methods: In this study, 800 (407f/393 m) subjects volunteered aged from 21 to 60 years. Both genders were divided into four age groups according to decades. The three-dimensional upper body posture was measured by using the rasterstereography (ABW-Bodymapper). The habitual static posture was measured in two dental occlusion conditions (a) in rest position and (b) symmetrical blocking in the bicuspid region by cotton rolls.
Results: A significant reduction of the trunk length (0.72 mm; p < 0.001), an increase of the lumbar (0.30°; p < 0.001) and the thoracic bending angle (0.14°; p = 0.001), a reduction of the spinal forward decline (0.16°; p < 0.001) and a reduction of the scapular distance (0.36 mm; p = 0.001) was found. Gender-specific reactions can only be recorded in scapular distance, in that regard men reduce this distance while over all age groups women did not show a significant change.
Discussion: Slight gender- and age-independent reactions due to a symmetric occlusion blockade are shown: A gender independent reaction of the spinal related variables in the sagittal plane (thoracic and lumbar flexion angle, trunk length, spinal forward decline). In addition, a gender specific change of the shoulder blade distance could be observed, where men reduced the distance while female did not show a change. However, since these reactions are of a minimum amount, it can be concluded that neurophysiological compensation mechanisms work equally well regardless of age and sex, and the upper body posture of healthy people changes only very slightly due to a temporarily symmetrical altered bite position.
Significant reductions in stratospheric ozone occur inside the polar vortices each spring when chlorine radicals produced by heterogeneous reactions on cold particle surfaces in winter destroy ozone mainly in two catalytic cycles, the ClO dimer cycle and the ClO/BrO cycle. Chlorofluorocarbons (CFCs), which are responsible for most of the chlorine currently present in the stratosphere, have been banned by the Montreal Protocol and its amendments, and the ozone layer is predicted to recover to 1980 levels within the next few decades. During the same period, however, climate change is expected to alter the temperature, circulation patterns and chemical composition in the stratosphere, and possible geo-engineering ventures to mitigate climate change may lead to additional changes. To realistically predict the response of the ozone layer to such influences requires the correct representation of all relevant processes. The European project RECONCILE has comprehensively addressed remaining questions in the context of polar ozone depletion, with the objective to quantify the rates of some of the most relevant, yet still uncertain physical and chemical processes. To this end RECONCILE used a broad approach of laboratory experiments, two field missions in the Arctic winter 2009/10 employing the high altitude research aircraft M55-Geophysica and an extensive match ozone sonde campaign, as well as microphysical and chemical transport modelling and data assimilation. Some of the main outcomes of RECONCILE are as follows: (1) vortex meteorology: the 2009/10 Arctic winter was unusually cold at stratospheric levels during the six-week period from mid-December 2009 until the end of January 2010, with reduced transport and mixing across the polar vortex edge; polar vortex stability and how it is influenced by dynamic processes in the troposphere has led to unprecedented, synoptic-scale stratospheric regions with temperatures below the frost point; in these regions stratospheric ice clouds have been observed, extending over >106km2 during more than 3 weeks. (2) Particle microphysics: heterogeneous nucleation of nitric acid trihydrate (NAT) particles in the absence of ice has been unambiguously demonstrated; conversely, the synoptic scale ice clouds also appear to nucleate heterogeneously; a variety of possible heterogeneous nuclei has been characterised by chemical analysis of the non-volatile fraction of the background aerosol; substantial formation of solid particles and denitrification via their sedimentation has been observed and model parameterizations have been improved. (3) Chemistry: strong evidence has been found for significant chlorine activation not only on polar stratospheric clouds (PSCs) but also on cold binary aerosol; laboratory experiments and field data on the ClOOCl photolysis rate and other kinetic parameters have been shown to be consistent with an adequate degree of certainty; no evidence has been found that would support the existence of yet unknown chemical mechanisms making a significant contribution to polar ozone loss. (4) Global modelling: results from process studies have been implemented in a prognostic chemistry climate model (CCM); simulations with improved parameterisations of processes relevant for polar ozone depletion are evaluated against satellite data and other long term records using data assimilation and detrended fluctuation analysis. Finally, measurements and process studies within RECONCILE were also applied to the winter 2010/11, when special meteorological conditions led to the highest chemical ozone loss ever observed in the Arctic. In addition to quantifying the 2010/11 ozone loss and to understand its causes including possible connections to climate change, its impacts were addressed, such as changes in surface ultraviolet (UV) radiation in the densely populated northern mid-latitudes.
The international research project RECONCILE has addressed central questions regarding polar ozone depletion, with the objective to quantify some of the most relevant yet still uncertain physical and chemical processes and thereby improve prognostic modelling capabilities to realistically predict the response of the ozone layer to climate change. This overview paper outlines the scope and the general approach of RECONCILE, and it provides a summary of observations and modelling in 2010 and 2011 that have generated an in many respects unprecedented dataset to study processes in the Arctic winter stratosphere. Principally, it summarises important outcomes of RECONCILE including (i) better constraints and enhanced consistency on the set of parameters governing catalytic ozone destruction cycles, (ii) a better understanding of the role of cold binary aerosols in heterogeneous chlorine activation, (iii) an improved scheme of polar stratospheric cloud (PSC) processes that includes heterogeneous nucleation of nitric acid trihydrate (NAT) and ice on non-volatile background aerosol leading to better model parameterisations with respect to denitrification, and (iv) long transient simulations with a chemistry-climate model (CCM) updated based on the results of RECONCILE that better reproduce past ozone trends in Antarctica and are deemed to produce more reliable predictions of future ozone trends. The process studies and the global simulations conducted in RECONCILE show that in the Arctic, ozone depletion uncertainties in the chemical and microphysical processes are now clearly smaller than the sensitivity to dynamic variability.
Genetic generalised epilepsy (GGE) is the most common form of genetic epilepsy, accounting for 20% of all epilepsies. Genomic copy number variations (CNVs) constitute important genetic risk factors of common GGE syndromes. In our present genome-wide burden analysis, large (≥ 400 kb) and rare (< 1%) autosomal microdeletions with high calling confidence (≥ 200 markers) were assessed by the Affymetrix SNP 6.0 array in European case-control cohorts of 1,366 GGE patients and 5,234 ancestry-matched controls. We aimed to: 1) assess the microdeletion burden in common GGE syndromes, 2) estimate the relative contribution of recurrent microdeletions at genomic rearrangement hotspots and non-recurrent microdeletions, and 3) identify potential candidate genes for GGE. We found a significant excess of microdeletions in 7.3% of GGE patients compared to 4.0% in controls (P = 1.8 x 10-7; OR = 1.9). Recurrent microdeletions at seven known genomic hotspots accounted for 36.9% of all microdeletions identified in the GGE cohort and showed a 7.5-fold increased burden (P = 2.6 x 10-17) relative to controls. Microdeletions affecting either a gene previously implicated in neurodevelopmental disorders (P = 8.0 x 10-18, OR = 4.6) or an evolutionarily conserved brain-expressed gene related to autism spectrum disorder (P = 1.3 x 10-12, OR = 4.1) were significantly enriched in the GGE patients. Microdeletions found only in GGE patients harboured a high proportion of genes previously associated with epilepsy and neuropsychiatric disorders (NRXN1, RBFOX1, PCDH7, KCNA2, EPM2A, RORB, PLCB1). Our results demonstrate that the significantly increased burden of large and rare microdeletions in GGE patients is largely confined to recurrent hotspot microdeletions and microdeletions affecting neurodevelopmental genes, suggesting a strong impact of fundamental neurodevelopmental processes in the pathogenesis of common GGE syndromes.
Experimental study of the ¹⁵O(2p,γ)¹⁷Ne cross section by Coulomb dissociation for the rp process
(2016)
The time-reversed reaction 15O(2p, γ)17Ne has been studied by the Coulomb dissociation technique. Secondary 17Ne ion beams at 500 AMeV have been produced by fragmentation reactions of 20Ne in a beryllium production target and dissociated on a secondary Pb target. The incoming beam and the reaction products have been identified with the kinematically complete LAND-R3B experimental setup at GSI. The excitation energy prior to decay has been reconstructed by using the invariant-mass method. The preliminary differential and integral Coulomb Dissociation cross sections (σCoul) have been calculated, which provide a photoabsorption (σphoto) and a radiative capture cross section (σcap). Additionally, important information about the nuclear structure of the 17Ne nucleus will be obtained. The analysis is in progress.
We have studied one-proton-removal reactions of about 500MeV/u 17Ne beams on a carbon target at the R3B/LAND setup at GSI by detecting beam-like 15O-p and determining their relative-energy distribution. We exclusively selected the removal of a 17Ne halo proton, and the Glauber-model analysis of the 16F momentum distribution resulted in an s2 contribution in the 17Ne ground state of about 40%.
Partial wave analysis of the reaction p(3.5 GeV) + p → pK +Λ to search for the "ppK−" bound state
(2015)
Employing the Bonn–Gatchina partial wave analysis framework (PWA), we have analyzed HADES data of the reaction p(3.5 GeV) + p → pK +Λ. This reaction might contain information about the kaonic cluster “ppK −” (with quantum numbers J P = 0− and total isospin I = 1/2) via its decay into pΛ. Due to interference effects in our coherent description of the data, a hypothetical KNN (or, specifically “ppK −”) cluster signal need not necessarily show up as a pronounced feature (e.g. a peak) in an invariant mass spectrum like pΛ. Our PWA analysis includes a variety of resonant and non-resonant intermediate states and delivers a good description of our data (various angular distributions and two-hadron invariant mass spectra) without a contribution of a KNN cluster. At a confidence level of CLs = 95% such a cluster cannot contribute more than 2–12% to the total cross section with a pK +Λ final state, which translates into a production cross-section between 0.7 μb and 4.2 μb, respectively. The range of the upper limit depends on the assumed cluster mass, width and production process.
Background: Eligibility criteria are a critical part of clinical trials, as they define the patient population under investigation. Besides certain patient characteristics, clinical trials often include biomarker testing for eligibility. However, patient-identification mostly relies on the trial site itself and is often a time-consuming procedure, which could result in missing out on potentially eligible patients. Pre-selection of those patients using a registry could facilitate the process of eligibility testing and increase the number of identified patients. One aim with the PRAEGNANT registry (NCT02338167) is to identify patients for therapies based on clinical and molecular data. Here, we report eligibility testing for the SHERBOC trial using the German PRAEGNANT registry.
Methods:Heregulin (HRG) has been reported to identify patients with better responses to therapy with the anti-HER3 monoclonal antibody seribantumab (MM-121). The SHERBOC trial investigated adding seribantumab (MM-121) to standard therapy in patients with advanced HER2-negative, hormone receptor–positive (HR-positive) breast cancer and HRG overexpression. The PRAEGNANT registry was used for identification and tumor testing, helping to link potential HRG positive patients to the trial. Patients enrolled in PRAEGNANT have invasive and metastatic or locally advanced, inoperable breast cancer. Patients eligible for SHERBOC were identified by using the registry. Study aims were to describe the HRG positivity rate, screening procedures, and patient characteristics associated with inclusion and exclusion criteria.
Results: Among 2769 unselected advanced breast cancer patients, 650 were HER2-negative, HR-positive and currently receiving first- or second-line treatment, thus potentially eligible for SHERBOC at the end of current treatment; 125 patients also met further clinical eligibility criteria (e.g. menopausal status, ECOG). In the first/second treatment lines, patients selected for SHERBOC based on further eligibility criteria had a more favorable prognosis than those not selected. HRG status was tested in 38 patients, 14 of whom (36.8%) proved to be HRG-positive.
Conclusion: Using a real-world breast cancer registry allowed identification of potentially eligible patients for SHERBOC focusing on patients with HER3 overexpressing, HR-positive, HER2-negative metastatic breast cancer. This approach may provide insights into differences between patients eligible or non-eligible for clinical trials.
Trial registration: Clinicaltrials, NCT02338167, Registered 14 January 2015 - retrospectively registered.
Purpose: The aim of this official guideline coordinated and published by the German Society for Gynecology and Obstetrics (DGGG) and the German Cancer Society (DKG) was to optimize the screening, diagnosis, therapy and follow-up care of breast cancer.
Methods: The process of updating the S3 guideline dating from 2012 was based on the adaptation of identified source guidelines which were combined with reviews of evidence compiled using PICO (Patients/Interventions/Control/Outcome) questions and the results of a systematic search of literature databases and the selection and evaluation of the identified literature. The interdisciplinary working groups took the identified materials as their starting point to develop recommendations and statements which were modified and graded in a structured consensus procedure.
Recommendations: Part 1 of this short version of the guideline presents recommendations for the screening, diagnosis and follow-up care of breast cancer. The importance of mammography for screening is confirmed in this updated version of the guideline and forms the basis for all screening. In addition to the conventional methods used to diagnose breast cancer, computed tomography (CT) is recommended for staging in women with a higher risk of recurrence. The follow-up concept includes suggested intervals between physical, ultrasound and mammography examinations, additional high-tech diagnostic procedures, and the determination of tumor markers for the evaluation of metastatic disease.
Ziele: Das Ziel dieser offiziellen Leitlinie, die von der Deutschen Gesellschaft für Gynäkologie und Geburtshilfe (DGGG) und der Deutschen Krebsgesellschaft (DKG) publiziert und koordiniert wurde, ist es, die Früherkennung, Diagnostik, Therapie und Nachsorge des Mammakarzinoms zu optimieren.
Methoden: Der Aktualisierungsprozess der S3-Leitlinie aus 2012 basierte zum einen auf der Adaptation identifizierter Quellleitlinien und zum anderen auf Evidenzübersichten, die nach Entwicklung von PICO-(Patients/Interventions/Control/Outcome-)Fragen, systematischer Recherche in Literaturdatenbanken sowie Selektion und Bewertung der gefundenen Literatur angefertigt wurden. In den interdisziplinären Arbeitsgruppen wurden auf dieser Grundlage Vorschläge für Empfehlungen und Statements erarbeitet, die im Rahmen von strukturierten Konsensusverfahren modifiziert und graduiert wurden.
Empfehlungen: Der Teil 1 dieser Kurzversion der Leitlinie zeigt Empfehlungen zur Früherkennung, Diagnostik und Nachsorge des Mammakarzinoms: Der Stellenwert des Mammografie-Screenings wird in der aktualisierten Leitlinienversion bestätigt und bildet damit die Grundlage der Früherkennung. Neben den konventionellen Methoden der Karzinomdiagnostik wird die Computertomografie (CT) zum Staging bei höherem Rückfallrisiko empfohlen. Die Nachsorgekonzepte beinhalten Untersuchungsintervalle für die körperliche Untersuchung, Ultraschall und Mammografie, während weiterführende Gerätediagnostik und Tumormarkerbestimmungen bei der metastasierten Erkrankung Anwendung finden.
Die Beurteilung von Standortseigenschaften ist eine der wichtigsten forstwirtschaftlichen Voraussetzungen für eine standörtlich angepasste Baumartenwahl. Die traditionelle Standortskartierung Bayerns klassifiziert forstlich relevante Bodeneigenschaften mit einem nominal- und ordinal-skalierten 3-ziffrigen Standortsschlüssel. Im physiographisch
ausgelegten Bayerischen Standortsinformationssystem BaSIS hingegen werden Bodeneinheiten der ÜBK 1 : 25.000 (Übersichtsbodenkarte des Bayerischen Landesamts für Umwelt) mit quantitativen Bodenkenndaten aus zugewiesenen Leitprofilen belegt (nutzbare Feldkapazität, Trockenrohdichte, volumetrischer Skelettgehalt, Tiefenverlauf der Basensättigung u. a.). Ziel dieser Studie ist es, den gutachterlichen Entscheidungsprozess der terrestrischen Wasserhaushaltsstufen (WHH-Stufen) der Standortskartierung unter Verwendung klimatischer und bodenkundlicher Größen statistisch nachzubilden. Datengrundlage sind 1.349 Profile des Bodeninformationssystems des Bayerischen Landesamts für Umwelt, die mit der Standortskarte und Klimakarten verschnitten wurden. Um die Aussagekraft der WHH-Stufe bezüglich der standörtlichen Trockenstress-Gefährdung zu verstehen, wird das Erklärungsmodell der WHH-Stufen mit zwei deterministischen Trockenstress-Größen unterschiedlich komplexer Wasserhaushaltsmodelle verglichen. Der Vergleich zeigt klar, dass die Transpirationsdifferenz TDiff als eine der beiden deterministischen Trockenstress-Größen und gleichzeitig Grundlage zur Ansprache des Wasserhaushalts in BaSIS wesentlich stärker niederschlagsgetrieben ist als die WHH-Stufe der Standortskartierung. In einem letzten Schritt wird – ermutigt durch eine relativ erfolgreiche Nachbildung der WHH-Stufen – das Potential der WHH-Stufen zur Schätzung der nutzbaren Feldkapazität als einer der wichtigsten bodenkundlichen Kennwerte untersucht. Dabei zeigt sich, dass der Einbezug der Standortskartierung in physiographisch basierte Standortsinformationssysteme die Schätzung dieser Parameter verbessern kann. Für die Praxis-Umsetzung empfiehlt sich, stärker nach den Bodeneinheiten oder aggregierten Bodeneinheiten zu differenzieren und Expertenwissen einzubeziehen. Zusammengefasst stellt diese Studie einen Brückenschlag zwischen den genannten Systemen her. Sie bringt einen Erkenntnisgewinn auf beiden Seiten und unterstützt die Kommunikation zwischen Nutzern des einen oder anderen Systems.
Die fünf Abschnitte der Meteor-Reise 48 führen in die Zone der Ostrandzirkulation des Südost-Atlantiks und verknüpfen ozeanografische, biologische, geologische und chemische Arbeiten im Bereich des Auftriebsgebietes vor der südwest-afrikanischen Küste sowie im Pelagial des Angolabeckens und des Kapbeckens. Die Arbeiten konzentrieren sich auf · die Biodiversität von Benthosgemeinschaften in Tiefseebecken, · biogeochemische Stoffkreisläufe und kurzskalige holozäne Klimavariationen im Auftriebsgebiet vor Namibia, · die Dynamik des Angola Domes und des Benguelastromes und die Entstehung des Südäquatorialen Gegenstroms im Atlantik, · die Verteilungen von Spurenelementen und natürlichen Radionukliden im Auftriebsgebiet vor Namibia, · den Einfluss mesoskaliger physikalischer Strukturen und Prozesse auf die Produktion des Zooplanktons im nördlichen Benguela-Auftriebssystem.
We collected 6251 adult epigeic spiders from the dwarf-shrub heath to subalpine coniferous forest on Alp Flix (CH, canton Grisons, 1950 m) between May 2005 and May 2006 using pitfall traps. Total species richness and activity density of all species decreased from the open land to the forest, although this pattern varied according to family. The distribution of the 102 species found indicates that the small area around a single tree at the timberline provides habitats for both open land and forest spider species as well as some possible timberline specialists. Five species were new to the canton Grisons: Centromerita bicolor, Centromerita concinna, Hilaira excisa, Meioneta alpica and Tallusia experta. Three species showed remarkable morphological characteristics and were analysed in more detail. We found males of Pelecopsis radicicola without the characteristic longitudinal depression on the raised carapace. It is shown that the males of Meioneta alpica have a considerably variable lamella characteristica, which is nevertheless distinct from the sister species Meioneta ressli. Because we found intermediate forms of the head region described for Metopobactrus prominulus and M. schenkeli, respectively, M. schenkeli is considered a syn. nov. of M. prominulus. This study shows that the known distribution and taxonomic status of various spider taxa in the Central Alps are still incomplete and further work on arthropods in remote areas should be strongly encouraged.
Vasointestinal peptide metabolism plays a key physiological role in multimodular levels of vasodilatory, smooth muscle cell proliferative, parenchymal, and inflammatory lung reactions. In animal studies, vasointestinal peptide relaxes isolated pulmonary arterial segments from several mammalian species in vitro and neutralizes the pulmonary vasoconstrictor effect of endothelin. In some animal models, it reduces pulmonary vascular resistance in vivo and in monocrotaline-induced pulmonary hypertension. A 58-year-old woman presented with dyspnea and mild edema of the lower extremities. A bronchoscopy was performed without any suspicious findings suggesting a central tumor or other infiltrative disease. Endobronchial ultrasound revealed enlarged pulmonary arteries containing thrombi, a few enlarged lymph nodes, and enlarged mediastinal tissue anatomy with suspicion for mediastinal infiltration of a malignant process. We estimated that less than 10% of the peripheral vascular bed of the lung was involved in direct consolidated fibrosis as demonstrated in the left upper lobe apex. Further, direct involvement of fibrosis around the main stems of the pulmonary arteries was assumed to be low from positron emission tomography and magnetic resonance imaging scans. Assuming a positive influence of low-dose radiation, it was not expected that this could have reduced pulmonary vascular resistance by over two thirds of the initial result. However; it was noted that this patient had idiopathic pulmonary arterial hypertension mixed with "acute" (mediastinal) fibrosis which could have contributed to the unexpected success of reduction of pulmonary vascular resistance. To the best of our knowledge, this is the first report of successful treatment of idiopathic pulmonary arterial hypertension, probably as a result of low-dose radiation to the pulmonary arterial main stems. The patient continues to have no specific complaints concerning her idiopathic pulmonary arterial hypertension.
We have isolated a cDNA coding for a putative invertebrate-type dopamine receptor (Peadop2) from P. americana brain by using a PCR-based strategy. The mRNA is present in samples from brain and salivary glands. We analyzed the distribution of the PeaDOP2 receptor protein with specific affinity-purified polyclonal antibodies. On Western blots, PeaDOP2 was detected in protein samples from brain, subesophageal ganglion, thoracic ganglia, and salivary glands. In immunocytochemical experiments, we detected PeaDOP2 in neurons with their somata being located at the anterior edge of the medulla bilaterally innervating the optic lobes and projecting to the ventro-lateral protocerebrum. In order to determine the functional and pharmacological properties of the cloned receptor, we generated a cell line constitutively expressing PeaDOP2. Activation of PeaDOP2-expressing cells with dopamine induced an increase in intracellular cAMP. In contrast, a C-terminally truncated splice variant of this receptor did not exhibit any functional property by itself. The molecular and pharmacological characterization of the first dopamine receptor from P. americana provides the basis for forthcoming studies focusing on the significance of the dopaminergic system in cockroach behavior and physiology.