Search

Die Gefahr der Chronifizierung mit allen nachteiligen Folgen einer chronischen Schmerzerkrankung ist bei Wirbelsaulenschmerzen besonders gros und muss unter allen Umstanden hintangehalten werden.

Objectives Medical laboratories may, at their own discretion, exceed but not undercut regulatory quality requirements. Available economic resources, however, may drive or hinder eagerness to exceed minimum requirements. Depending on the respective scopes of regulatory and economic framework conditions, differing levels of quality efforts to safeguard laboratory performance can be anticipated. However, this has not yet been investigated. Methods Immunohaematology external quality assessment (EQA) results collected by 26 EQA providers from their participant laboratories in 73 countries from 2004 to 2019 were evaluated. Error rates were aggregated in groups according to the respective national regulatory and economic framework conditions, to whether or not expert advice was provided in case of incorrect results, and the frequency of EQA samples. Results These representative data indicate no association between national regulatory (mandatory participation in EQA, monitoring of performance of individual laboratories by authorities, financial consequences of incorrect results) and economic (level of national income, share of national health expenditure) conditions to the quality performance of medical laboratories in immunohaematology. However, EQA providers’ support for laboratories in the event of incorrect results appear to be associated with lower error rates, but a high EQA sample frequency with higher error rates. Conclusions Further research into the impact of introducing or changing services of EQA providers is needed to confirm the results found in this first of its kind study.

To investigate whether women with red blood cell (RBC)Retrospective study involving all singleton pregnancies affected by RBC alloimmunization and without pre-existing maternal bleeding disorders or placenta previa, from 1 July 1999 to 30 June 2019 ("cases"). Only bleedings not related to invasive procedures (amnio- or cordocenteses) were included. Patients who were already at increased risk of pre- or perinatal bleeding due to their medical history (pre-existing bleeding disorders, antithrombotic therapy), or known obstetrics parameters (placental abnormalities etc.) were not included a priori. Cases were compared to controls without RBC alloimmunization, matched for maternal age and body mass index, from the same tertiary referral center in Austria.130 cases were compared to 130 controls. Cases had significantly more previous pregnancies and miscarriages and their newborns had lower birthweight and were more often transferred to the intensive care unit than newborns of controls. 18/130 (13.8%) cases, compared to 8/130 (6.2%) controls experienced any bleeding during pregnancy or delivery (p = 0.061). Bleeding most often happened during the third trimester (cases: 4.6% vs. controls 0.8%, p = 0.12) and during or after delivery (cases: 7.7% vs. controls: 4.6%, p = 0.168). Binary logistic regression for the prediction of any bleeding complication during pregnancy, delivery or postpartum revealed immunization against RBC antigens as the only independent contributor (p = 0.04). Age, smoking, or previous obstetric history had no influence on the likelihood of maternal bleeding complications. Neither RBC antibody specificity nor titers were predictive of maternal bleeding during pregnancy or delivery.Pregnancies affected by RBC alloimmunization might be at increased risk of maternal bleeding complications during pregnancy and delivery.

The Rh blood group system plays a key role in transfusion and organ transplant medicine. The complex transmembrane Rh polypeptides RhD and RhCE carry numerous antigens, including the extremely immunogenic D antigen. The Rh polypeptides form multimolecular Rh complexes with certain transmembrane and skeletal proteins, with so far only incompletely understood physiological functions. Determination of the energy landscape of individual Rh binding epitopes towards their specific interaction partners as well as their localization across the red blood cell (RBC) membrane requires single molecule approaches including large area high resolution recognition imaging. Atomic force microscopy based molecular recognition force spectroscopy in combination with single molecule recognition imaging fulfills these requirements. For unbiased single molecule results, nano-mechanical influences due to cell elasticity have to be eliminated. This is realized by generation of ultra flat erythrocyte ghosts on a solid support. We developed a protocol for the preparation of complete ultraflat erythrocyte ghosts and determined the molecular binding behaviour of different anti-D antibodies towards their binding epitopes on RhD positive and negative erythrocytes. Performing optimized topography and recognition imaging at 16 Mpixel resolution allowed localisation of individual RhD molecules at the single molecule level across an entire RBC. A map of Rh antigens across integer ultraflat RBC ghosts was generated with nanometer resolution. Here we show a homogeneous distribution on rim and dimple regions with comparable receptor densities. Furthermore, differences in the energy landscape between specific monoclonal antibodies were determined at the single molecule level.

Background: Routine ABO blood group typing for pre-transfusion testing of a male Austrian patient of Far Eastern origin showed discrepant results with an apparently weak blood group B phenotype and irregular anti-B. Materials and Methods: ABH phenotyping and cross-matching was done by standard serologic techniques and levels of H expression were determined by flow cytometry. ABO gene sequencing including regulatory regions as well as analysis of FUT1 (H), FUT2 (Secretor), and FUT3 (Lewis) were carried out. Results: While monoclonal ABO antigen typing indicated blood group O, weak agglutination reactions using polyclonal human anti-B and anti-AB were seen. In reverse typing at room temperature, the plasma was reactive with A1 and A2 RBCs and negative with B and O cells, whereas at 4°C, anti-B reactivity was found. The indirect anti-globulin cross-match of the patient’s plasma was positive with group B RBCs and negative with group O RBCs. Sequencing analysis showed the presence of ABO*B.01 (B114) allele and homozygosity for the FUT1 mutation c.551_552delAG. Flow cytometry demonstrated trace amounts of H antigen on the patient’s RBCs. Conclusion: While a functional B allele was found, analysis of FUT1 and FUT2 genes revealed the presence of a rare para-Bombay genotype OhB. Interestingly, no anti-H but irregular anti-B was found in the patient’s plasma, responsible for the positive cross-match with group B RBCs. Even though very rare and not reported for the European population, the presence of an H-deficient phenotype should be considered when investigating individuals with an unusual ABO blood group type.

In the last decade, in many European Countries more and more measures have been initiated aiming at the prevention of food losses and wastes along the entire value chain. In order to evaluate or monitor such important measures it is crucial to obtain quantitative information on generated food waste amounts, subsequently enabling the quantitative evaluation of the measure's outcomes and efficiency. Currently there is a paucity of quantitative information, particularly on food losses that are directly generated during harvesting processes. Up to date, no method is available or standardised aiming at the in-situ or on-site quantification of food losses during harvest. Using the example of the potato harvest, this study presents a practical approach for determining potato losses. To test the applicability of the developed method, on-site measurements were conducted directly on the field at five different locations in Austria and Germany. Our method enables the quantification of food losses based on defined areas along the harvested potato rows, where the analyser manually collects potatoes during their harvest. Hereby, two types of potato losses needs to be considered: non-harvested, under-sized potatoes that remain under the earth and the harvested ones, which are rejected on-site because of quality requirements regarding their size, shape, and state of health. Our study shows that between 1 and 9% of field losses (based on yield potential) can be generated during the potato harvest. In future, this method may be the basis for standardised protocols in order to be able to derive cultivar-specific benchmarks and, consequently, to develop measures for preventing food losses. In general, more case studies and evidence-based ground-up measurements on other cultivars and for other regions are needed focusing on the on-site quantification of post-harvest losses.

Background ISO 9001 and ISO 15189 have been established as continuative models for quality systems beyond national laws, mandatory standards and guidelines of expert associations regarding analytical and organisational performance of medical laboratories and transfusion services. Although widely used, their impact on laboratory performance has not been investigated. Methods We retrospectively analysed the results of 167 laboratories in 59 distributions of the Austrian red cell immunohaematology external quality assessment (EQA) scheme in the years 1999–2017. The performance for each parameter and trends of individual participants were compared with respect to certification or accreditation status of participants’ quality systems and to laboratory type. Results Considering more than 52,000 EQA results, the absence or presence of a laboratory quality management system showed different error rates. Laboratories with ISO 9001 or ISO 15189 certification/accreditation had 0.7% incorrect results, while this rate was doubled without such quality systems (1.4%, p=0.0002). Statistically significant error reductions were seen upon ISO 9001/ISO 15189 implementation (1.3% before vs. 0.7% after; p=0.0468). Transfusion services had fewer errors (0.9%) compared to hospital and independent laboratories (both 1.2%). Conclusions Implementation and maintenance of quality systems according to ISO 9001 or ISO 15189 as well as laboratory specialisation result in better analytical performance as can be seen in immunohaematology EQA results. The conclusion is that these results apply to other laboratory tests and perhaps to other areas of health care.

Настоящее исследование вечной мерзлоты, обнаженной на утесе Собо-Сисе, обеспечивает всестороннюю криостратиграфическую характеристику и свойства органического вещества. Это дает представление о разрастании и деградации вечной мерзлоты за последние ⁓52 тысячи лет, а также о климатическом и морфодинамическом контроле динамики вечной мерзлоты регионального масштаба в прибрежном районе моря Лаптевых в северо-восточной части Сибири. Скала Собо-Сисе Едома - один из самых быстро разрушающихся островов, сложенных вечной мерзлотой в масштабах всей Арктики, здесь происходит значительный сброс органического вещества в реку Лена., The present study of the permafrost exposed at the Sobo-Sise Yedoma cliff provides a comprehensive cryostratigraphic and organic matter inventory. It gives insight into permafrost aggradation and degradation over the last about 52 thousand years and into their climatic and morphodynamic controls on regional-scale permafrost dynamics of the Central Laptev Sea coastal region in NE Siberia. The Sobo-Sise Yedoma cliff is one of the fastest eroding permafrost features arctic-wide and releases considerable amounts of organic matter into the Lena River.

The applicability of the High-Order Spectral Method (HOSM) as a very fast non-linear method for deterministic short-term wave prediction is discussed within this paper. The focus lies on the systematic experimental validation of the HOSM in order to identify and evaluate possible areas of application as well as limitations of use. For this purpose, irregular sea states with varying parameters such as wave steepness and underlying wave spectrum are addressed by numerical simulations and model tests in the controlled environment of a seakeeping basin. In addition, the influence of the propagation distance is discussed. For the evaluation of the accuracy of the HOSM prediction, the surface similarity parameter (SSP) is utilized, allowing a quantitative validation of the results. The results obtained are compared to linear wave prediction to discuss the pros and cons of a non-linear deterministic short-term wave prediction. In conclusion, this paper shows that the non-linear deterministic wave prediction based on HOSM leads to a substantial improvement of the prediction quality for moderate and steep irregular wave trains in terms of individual waves and prediction distance.

This paper explores the applicability of envelope soliton solutions of the non-linear Schrodinger-type equation as an innovative design wave for wave–structure interaction investigations. The major benefits of envelope solitons are the potential to generate non-linear wave groups of certain frequency and (physically possible) wave steepness as well as the availability of an analytical solution. Furthermore, the fact that envelope solitons are characterized by a limiting frequency bandwidth enables the tailor-made generation of critical wave conditions for task-specific wave–structure investigations. For the evaluation of the applicability of envelope solitons, wave–structure investigations with a chemical tanker were performed in a set of envelope solitons at certain frequencies and wave steepness. The applicability of envelope solitons as design waves as well as their impact on the chemical tanker are compared to classical design wave concepts and tailored extreme wave events. For the extreme wave events, the Peregrine breather solution and a real world abnormal wave reproduction, the famous ‘New Year Wave’, were selected. The investigations comprised model tests as well as numerical simulations. Altogether, this paper shows that envelope solitons are excellent design waves for extreme response investigations suitable for model tests as well as numerical investigations.

When grown on a non-penetretable at a surface angle of 45°, Arabidopsis roots form wave-like structures and, in wild type rarely, but in certain mutants the tip root even may form circles. These circles are called coils. The formation of coils depends on the complex interaction of circumnutation, gravitropism and negative thigmotropism where - at least - gravitropism is intimately linked to auxin transport and signaling. The knockout mutant of patatin-related phospholipase-AI-1 (pplaI-1) is an auxin-signaling mutant which forms moderately increased numbers of coils on tilted agar plates. We tested the effects of the auxin efflux transport inhibitor NPA (1-naphthylphtalamic acid) and of the influx transport inhibitor 1-NOA (1-naphthoxyacetic acid) which both further increased root coil formation. The pPLAI-1 inhibitors HELSS (haloenol lactone suicide substrate=E-6-(bromomethylene)tetrahydro-3-(1-naphthalenyl)-2H-pyran-2-one) and ETYA (eicosatetraynoic acid) which are auxin signaling inhibitors also increased coil formation. In addition, far red light treatment increased coil formation. The results point out that a disturbance of auxin transport and signaling is one potential cause for root coils. As we show that the mutant pplaI-1 penetrates horizontal agar plates better than wild type plants root movements may help penetrating the soil.

Background: As some errors in pretransfusion testing remain unrecognized, error rates and the resulting need for corrective measures are probably underestimated. External quality assessment (EQA) schemes could provide valuable input for identifying error-prone laboratory tests because they are designed to monitor test performance and errors. So far, however, there are only limited published data on error rates in such schemes. Methods: The types and incidence of incorrect results in an EQA scheme for red cell immunohematology with 187 participating laboratories were examined. The results of 58 distributions between 1999 and 2017 were evaluated, considering also the employed determination methods. Results: Out of a total of 58,726 results, 563 (0.96%) were incorrect. Error rates were 5.45% for antibody identification, 1.39% for Rh phenotyping, 0.83% for serologic cross-match, 0.60% for direct antiglobulin test, 0.20% for Kell phenotyping, 0.16% for antibody screening, and 0.14% for ABO phenotyping. During the observation period, 53 participants reported error-free results, while 37 reported one incorrect result and 97 repeatedly reported incorrect results for one or more analytes. Error rates obtained by manual methods significantly surpassed those obtained by automated methods (1.04 vs. 0.42%). The introduction of double testing with two different systems reduced error rates in Rh phenotyping from 1.55 to 0.50%. Conclusion: Risk assessment should consider that error rates in pretransfusion test results vary. These data delineate the error risk potential of individual laboratory tests and thus should aid in tailoring appropriate improvement measures.

Background and objectives Classical neutrophil-reactive antibody testing depends on the quick isolation of neutrophils from freshly taken whole blood. To allow a better logistic preparation before testing, the influence of time interval between venipuncture and cell isolation has been evaluated in this study. Materials and methods Neutrophils and whole leukocytes were isolated from EDTA whole blood immediately (T0) as well as 4, 8 and 24 h after blood donation (T4, T8 and T24). These cells were tested against reference sera containing antibodies against HNA-1b, −2, −3a and HLA class I using granulocyte aggregation test (GAT), microscopic granulocyte immunofluorescence test (GIFT) and flow-cytometric white blood cell immunofluorescence test (Flow-GIFT/WIFT). Results GAT was the most error-prone test displaying overall weaker aggregation strengths already at T4 (overall accuracy OA = 0.72, κ = 0.58). GIFT results showed good agreement at T4 (OA = 0.86, κ = 0.79) and remained stable until T8, while test results were slightly impaired at T24 (OA = 0.71, κ = 0.55). Flow-GIFT/WIFT was identified as the most robust screening method, remaining stable even at T24. Calculated ratios (sample/negative control) decreased non-significantly and remained highly above the cut-off in all samples. Conclusion Acceptable time limits for cell isolation are different for each screening method investigated. For GAT, cell isolation should be performed within 4 h, while GIFT tolerates a neutrophil isolation delay of 8 h. Flow-GIFT/WIFT isolation can be performed even after 24 h without impairment of the results. Using the latter test as a stand-alone pre-screening test, whole blood can be used from donors who are not directly accessible.

The novel in‐frame deletion is associated with a considerably reduced expression of D antigen and a variant RhD phenotype. The mutation occurs in close proximity to the first exofacial loop of the protein which is mainly encoded by sequences of Exon 1. Structural changes caused by the deletion may reach the surface of the protein in this region. Consistent with the substantially weakened agglutination reactions observed with anti‐D LHM59/19, the presence of an altered Loop 1–dependent epitope 8.15 appears to be possible. Although all the anti‐Ds we used to examine the epitope pattern reacted positive with the proposita's RBCs, the presence of a qualitatively altered D antigen may not be excluded. The primigravida had not received prenatal or postnatal RhIG prophylaxis. Though pregnant with a D‐positive fetus, no immunization was observed; however, whether this novel D variant permits anti‐D immunization remains unclear. Hence, D‐negative transfusion in carriers and prophylactic use of RhIG in pregnancy is recommended. DMW expands the exceptionally rare RHD in‐frame deletions reported and should be regarded as a putative partial D allele.

Bei der biologischen Behandlung von organischen Abfallen konnen unter bestimmten Bedingungen treibhausrelevante Gasemissionen durch die Bildung von Lachgas und Methan entstehen. Durch die Verpflichtung zur getrennten Sammlung von biogenen Abfallen und deren Deponierungsverbot hat sich das Behandlungsaufkommen in den letzten Jahren deutlich erhoht. Damit sind auch die Treibhausgasemissionen aus der mechanisch-biologischen Vorbehandlung und der Kompostierung deutlich gestiegen. Die zugrunde liegenden Mechanismen der Freisetzung von Lachgas sind in naturlichen Systemen (wie Boden) noch nicht vollstandig geklart, und erst recht nicht in technischen Behandlungsanlagen, in denen organische Abfalle konzentriert anfallen und behandelt werden. Kompostierungsversuche im Labormasstab sollten helfen Randbedingungen zu finden, die die Emission von Lachgas reduzieren konnen. Dabei kamen neue innovative Messmethoden wie die Laser-Absorptionsspektroskopie zur kontinuierlichen Quantifizierung von Lachgas zum Einsatz. Es zeigte sich, dass ein kontinuierliches Monitoring der Prozesse unumganglich ist, da die Bildung und Freisetzung von Lachgas sehr sensibel auf Veranderungen der Rahmenbedingungen (z. B. Luft-/Sauerstoffzufuhr, C/N-Verhaltnis des Inputmaterials, pH-Wert) reagiert und im zeitlichen Verlauf sehr heterogen auftritt. In diesem Beitrag wird exemplarisch der Einfluss der Variationen des pH-Wertes des Inputmaterials und der Beluftungsmenge dargestellt. Es zeigte sich, dass unter bestimmten Umstanden die technische Intensivrottephase sogar als „Senke“ fur atmospharisches Lachgas dienen kann.

Polyamines (PA) are catabolised by two groups of amine oxidases, the copper-binding amine oxidases (CuAOs) and the FAD-binding polyamine oxidases (PAOs). Previously, we have shown that CuAO1 is involved in ABA associated growth responses and ABA- and PA-mediated rapid nitric oxide (NO) production. Here we report the differential regulation of expression of POLYAMINE OXIDASE2 of Arabidopsis (AtPAO2) in interaction with ABA, nitrate and ammonium. Without ABA treatment germination, cotyledon growth and fresh weight of pao2 knockdown mutants as well as PAO2OX over-expressor plants were comparable to those of the wild type (WT) plants irrespective of the N source. In the presence of ABA, in pao2 mutants cotyledon growth and fresh weights were more sensitive to inhibition by ABA while PAO2OX over-expressor plants showed a rather similar response to WT. When NO3(-) was the only N source primary root lengths and lateral root numbers were lower in pao2 mutants both without and with exogenous ABA. PAO2OX showed enhanced primary and lateral root growth in media with NO3(-) or NH4(+). Vigorous root growth of PAO2OX and the hypersensitivity of pao2 mutants to ABA suggest a positive function of AtPAO2 in root growth. ABA-induced NO production in pao2 mutants was lower indicating a potential contributory function of AtPAO2 in NO-mediated effects on root growth.

Mitogen-activated protein kinases (MAPKs) are a group of evolutionarily highly conserved ubiquitous proteins that have significant function as facilitators of signal transduction. Plant MAPK cascades regulate a variety of processes in development and stress responses. MAPKs play key roles in a wide array of abiotic and biotic stress responses, such as drought, salinity, high/low temperatures, wounding, and pathogen invasion. Cascades of MAPK relay signals primarily through reversibly phosphorylated MAPKs, namely, MAPK kinases (MAPKKs) and MAPK kinase kinases (MAPKKKs). MAPK, MAPKK, and MAPKKK are networked in specific signal transduction pathways that affect diverse upstream receptors and downstream target components. A number of components of the MAPK cascade are shown to be induced by a single stress. In most instances, a single MAPK module transmits multiple signals in plants. Identification of the mechanisms and functions of MAPK cascades in stress tolerance has practical value for improvement of crops. This article focuses on the recent knowledge on plant MAPK in abiotic stress responses.

In solid organ transplant recipients (SOTRs), long-term utilization of immunosuppressive therapy is a critical component of preventing graft rejection. Immunosuppression medications, however, inadvertently lead to decreased tumor surveillance; consequently, SOTRs represent a high-risk population for the development of malignant tumors. In particular, SOTRs are prone to developing skin cancers, which exhibit unique epidemiologic, pathophysiologic, and prognostic characteristics in this patient subset. In this chapter, we discuss the most commonly reported skin cancers in SOTRs: keratinocyte carcinomas (i.e., squamous cell carcinoma and basal cell carcinoma), Kaposi’s sarcoma, Merkel cell carcinoma, malignant melanoma, primary cutaneous posttransplantation lymphoproliferative disease (PTLD), cutaneous sarcomas, and appendageal carcinomas. Because these tumors are aggressive and tend to respond poorly to standard surgery, radiation therapy, and chemotherapy, SOTRs require patient education and motivational support, regular follow-up, and management by an interdisciplinary clinician team. Further research and clinical trials are warranted to improve treatment protocols.

This paper discusses the potential of deterministic wave prediction as one basic module for decision support of offshore operations. Therefore, methods of different complexity&mdash, the linear wave solution, the non-linear Schr&ouml, dinger equation (NLSE) of two different orders and the high-order spectral method (HOSM)&mdash, are presented in terms of applicability and limitations of use. For this purpose, irregular sea states with varying parameters are addressed by numerical simulations as well as model tests in the controlled environment of a seakeeping basin. The irregular sea state investigations focuses on JONSWAP spectra with varying wave steepness and enhancement factor. In addition, the influence of the propagation distance as well as the forecast horizon is discussed. For the evaluation of the accuracy of the prediction, the surface similarity parameter is used, allowing an exact, quantitative validation of the results. Based on the results, the pros and cons of the different deterministic wave prediction methods are discussed. In conclusion, this paper shows that the classical NLSE is not applicable for deterministic wave prediction of arbitrary irregular sea states compared to the linear solution. However, the application of the exact linear dispersion operator within the linear dispersive part of the NLSE increased the accuracy of the prediction for small wave steepness significantly. In addition, it is shown that non-linear deterministic wave prediction based on second-order NLSE as well as HOSM leads to a substantial improvement of the prediction quality for moderate and steep irregular wave trains in terms of individual waves and prediction distance, with the HOSM providing a high accuracy over a wider range of applications.

Background D antigen variants may be grouped into partial D, weak D, and DEL types. Cumulative phenotype frequencies of these D variants may approach 1% in certain European regions. Unambiguous and quick identification of D variants is of immediate clinical relevance, with implications for transfusion strategy. Study Design and Methods A total of 628 samples with ambiguous serologic results from different immunohematology laboratories throughout the Flanders region, Belgium, were genotyped using a commercially available weak D typing approach. After exclusion of detectable weak D types, molecular RHD exon scanning was performed for the remaining samples, and RHD sequencing was performed in two particular cases. Results Of all samples investigated, 424 (67.5%) were positive for weak D Type 1, 2, or 3, and 22 cases (3.5%) typed weak D Type 4.0/4.1/4.3, 4.2, 5, 11, 15, or 17. Another 49 (7.8%) samples were partial D variants, with a major proportion being category DVI types (n = 27). One RHD(S103P) sample was identified as high-grade partial D, with DIII-like phenotype and anti-D and anti-C immunization. Additionally, a novel DVI Type 3 (A399T) variant was found. Of the remaining 133 samples mainly tested because of ambiguous serologic D typing results due to recent transfusion, 32 (5.1%) were negative for RHD, and 101 (16.1%) were indistinguishable from wild-type RHD and not investigated further. Conclusion Despite the enormous diversity of RHD alleles, first-line weak D genotyping was remarkably informative, allowing for rapid classification of most samples with conspicuous RhD phenotype in Flanders. The clinical implications are discussed.

In this paper, the design and implementation of an institutional mentoring program for undergraduate medical students at the Medical University of Vienna are presented. Faculty members act as senior mentors in a small group setting enabling also peer mentoring (73.6% of mentees reporting a direct benefit from their co-mentees). Program acceptance by mentees and mentors is very high (71.7% of the mentees and 77.1% of the mentors giving the highest out of four rating categories). The adequacy of this program was studied by analyzing the topics discussed in the mentoring groups: the most frequently covered aspects are diploma thesis, clinical clerkship, studying abroad and career planning. Additionally, sex-specific distributions of mentor recruitment and selection as well as participation by students were documented (e.g., female proportion of 29.9% and 53.2% of mentors and mentees, respectively). Both feedback and content analysis demonstrate the success of this large-scale project.

Granulocyte-reactive antibodies may cause transfusion-related acute lung injury (TRALI) and immune neutropenias. Risk factors for their acquisition other than previous alloexposition are largely unknown. In addition to the known association between human leucocyte antigen alloantibodies and red blood cell alloimmunization in selected cohorts of transfused patients, this study investigated a possible extension of this association to granulocyte-reactive antibodies in women with a history of pregnancy. The overall prevalence of granulocyte-reactive antibodies in 333 samples from women with a history of pregnancy (143 samples containing red cell alloantibodies) was 23·1%. The prevalence in the red cell-alloimmunized group (32·9%) was significantly higher than in controls (15·8%, P

pPLA-I is the evolutionarily oldest patatin-related phospholipase A (pPLA) in plants, which have previously been implicated to function in auxin and defence signalling. Molecular and physiological analysis of two allelic null mutants for pPLA-I [ppla-I-1 in Wassilewskija (Ws) and ppla-I-3 in Columbia (Col) ] revealed pPLA-I functions in auxin and light signalling. The enzyme is localized in the cytosol and to membranes. After auxin application expression of early auxin-induced genes is significantly slower compared with wild type and both alleles show a slower gravitropic response of hypocotyls, indicating compromised auxin signalling. Additionally, phytochrome-modulated responses like abrogation of gravitropism, enhancement of phototropism and growth in far red-enriched light are decreased in both alleles. While early flowering, root coils and delayed phototropism are only observed in the Ws mutant devoid of phyD, the light-related phenotypes observed in both alleles point to an involvement of pPLA-I in phytochrome signalling.

Bacterial and archaeal lipids, such as glycerol dialkyl glycerol tetraethers (GDGTs) and dialkyl glycerol diethers, are increasingly used as proxies for specific environmental parameters, such as air temperature and soil pH in lacustrine environments. Little is known, however, about the distribution and applicability of bacterial and archaeal lipids on the Tibetan Plateau. We investigated nine different watersheds across the plateau by way of sediments from lakes and rivers, as well as the surrounding soils. Our transect study included a salinity gradient and focused on saline lakes, which are rarely examined. We analyzed archaeal isoprenoid (i) and bacterial branched (b) GDGTs, as well as archaeol to trace their sources and environmental factors, influencing their distributions. We could show that iGDGTs were produced in situ and bGDGTs were primarily soil-derived although we could not exclude in situ production of bGDGTs in the lakes. The most important environmental variables correlating with GDGT distributions were temperature and salinity. Bacterial GDGT distributions correlated mainly with salinity, while archaeal lipid distributions correlated with temperature. Based on the correlation of methylation (MBT′) and cyclisation (CBT) indices of bGDGTs with pH and mean annual air temperature (MAAT), we established local calibrations for the Tibetan lakes. TEX86 could also be applied to reconstruct temperature, which was strongly biased towards measured summer lake water temperature, indicating enhanced production of iGDGTs in the summer months. Existing proxies show, therefore, potential for palaeoclimate reconstruction on the Tibetan Plateau if local calibrations are applied.

Many different factors influence the propensity of transfusion recipients and pregnant women to form red blood cell alloantibodies (RBCA). RBCA may cause hemolytic transfusion reactions, hemolytic disease of the fetus and newborn and may be a complication in transplantation medicine. Antigenic differences between responder and foreign erythrocytes may lead to such an immune answer, in part with suspected specific HLA class II associations. Biochemical and conformational characteristics of red blood cell (RBC) antigens, their dose (number of transfusions and pregnancies, absolute number of antigens per RBC) and the mode of exposure impact on RBCA rates. In addition, individual circumstances determine the risk to form RBCA. Responder individuality in terms of age, sex, severity of underlying disease, disease- or therapy-induced immunosuppression and inflammation are discussed with respect to influencing RBC alloimmunization. For particular high-risk patients, extended phenotype matching of transfusion and recipient efficiently decreases RBCA induction and associated clinical risks.

How safe is ‘safe’? During the design phase of floating structures, specifications such as range of application, warranty of economical efficiency and reliability are integral parts of the evaluation process. The key decision is the choice of environmental design conditions to be considered for operation and survival: this issue cannot be solved globally, i.e. different operating conditions (transit, operation, survival) and criteria (body motions, local and global loads) will lead to individual results. In this paper a procedure for the systematic identification of critical (design) wave sequences for offshore structures is presented—a response based identification tool for critical wave sequence detection. The basic principle of this procedure is characterized by tailoring of short wave sequences to obtain a certain maximum response. The fully automated procedure combines wave/structure interaction analysis programs with an optimization algorithm. The objective is to find a critical wave sequence with respect to the predefined maximum responses. By means of this procedure, the identification and evaluation of critical design conditions can be conducted more systematically, accurately and thus efficiently. To demonstrate the broad scope of this procedure, a typical example is presented. The results obtained are reviewed against classical design methods. The investigations comprise numerical calculations as well as model test validations.

In the past years the existence of freak waves has been affirmed by observations, registrations, and severe accidents. One of the famous real-world registrations is the so-called “New Year Wave” recorded in the North Sea at the Draupner jacket platform on January 1, 1995. Since there is only a single point registration available, it is not possible to draw conclusions on the spatial development in front of and behind the point of registration, which is indispensable for a complete understanding of this phenomenon. This paper presents the temporal and spatial development of the “New Year Wave” generated in a seakeeping basin. This extreme sea state is measured at different locations in the tank, in a range from 2163 m (full scale) ahead of to 1470 m behind the target position—520 registrations altogether. The focus lies on the detailed description of a possible evolution of the “New Year Wave” over a large area. The group velocity, wave propagation and energy flux of this wave group as well as the wave kinematics and dynamics are analysed. As a case study a Ro/Ro vessel has been investigated in the “New Year Wave”, with special emphasis on the vertical bending moment.

Polyamines (PA), polyamine oxidases, copper amine oxidases, and nitric oxide (NO) play important roles in physiology and stress responses in plants. NO biosynthesis as a result of catabolism of PA by polyamine oxidases and copper amine oxidases may explain in part PA-mediated responses. Involvement of a copper amine oxidase gene, COPPER AMINE OXIDASE1 (CuAO1), of Arabidopsis was tested for its role in stress responses using the knockouts cuao1-1 and cuao1-2. PA-induced and ABA-induced NO production investigated by fluorometry and fluorescence microscopy showed that the cuao1-1 and cuao1-2 are impaired in NO production, suggesting a function of CuAO1 in PA and ABA-mediated NO production. Furthermore, we found a PA-dependent increase in protein S-nitrosylation. The addition of PA and ABA also resulted in H(2)O(2) increases. cuao1-1 and cuao1-2 showed less sensitivity to exogenous ABA supplementation during germination, seedling establishment, and root growth inhibition as compared to wild-type. In response to ABA treatment, expression levels of the stress-responsive genes RD29A and ADH1 were significantly lower in the knockouts. These observations characterize cuao1-1 and cuao1-2 as ABA-insensitive mutants. Taken together, our findings extend the ABA signal transduction network to include CuAO1 as one potential contributor to enhanced NO production by ABA.

Since we are living in the 'age of transcription', awareness of aspects other than transcription in auxin signal transduction seems to have faded. One purpose of this review is to recall these other aspects. The focus will also be on the time scales of auxin responses and their potential or known dependence on either AUXIN BINDING PROTEIN 1 (ABP1) or on TRANSPORT-INHIBITOR-RESISTANT1 (TIR1) as a receptor. Furthermore, both direct and indirect evidence for the function of ABP1 as a receptor will be reviewed. Finally, the potential functions of a two-receptor system for auxin and similarities to other two-receptor signalling systems in plants will be discussed. It is suggested that such a functional arrangement is a property of plants which strengthens tissue autonomy and overcomes the lack of nerves or blood circulation which are responsible for rapid signal transport in animals.

While the pro-differentiation and tumour suppressive functions of Notch signalling in keratinocytes are well established, the underlying mechanisms remain poorly understood. We report here that interferon regulatory factor 6 (IRF6), an IRF family member with an essential role in epidermal development, is induced in differentiation through a Notch-dependent mechanism and is a primary Notch target in keratinocytes and keratinocyte-derived SCC cells. Increased IRF6 expression contributes to the impact of Notch activation on growth/differentiation-related genes, while it is not required for induction of 'canonical' Notch targets like p21 WAF1/Cip1, Hes1 and Hey1. Down-modulation of IRF6 counteracts differentiation of primary human keratinocytes in vitro and in vivo, promoting ras-induced tumour formation. The clinical relevance of these findings is illustrated by the strikingly opposite pattern of expression of Notch1 and IRF6 versus epidermal growth factor receptor in a cohort of clinical SCCs, as a function of their grade of differentiation. Thus, IRF6 is a primary Notch target in keratinocytes, which contributes to the role of this pathway in differentiation and tumour suppression. The EMBO Journal (2011) 30, 4571-4585. doi:10.1038/emboj.2011.325; Published online 9 September 2011 Subject Categories: signal transduction; molecular biology of disease

AUXIN-BINDING PROTEIN 1 (ABP1) is not easily accessible for molecular studies because the homozygous T-DNA insertion mutant is embryo-lethal. We found that the heterozygous abp1/ABP1 insertion mutant has defects in auxin physiology-related responses: higher root slanting angles, longer hypocotyls, agravitropic roots and hypocotyls, aphototropic hypocotyls, and decreased apical dominance. Heterozygous plants flowered earlier than wild-type plants under short-day conditions. The length of the main root, the lateral root density and the hypocotyl length were little altered in the mutant in response to auxin. Compared to wild-type plants, transcription of early auxin-regulated genes (IAA2, IAA11, IAA13, IAA14, IAA19, IAA20, SAUR9, SAUR15, SAUR23, GH3.5 and ABP1) was less strongly up-regulated in the mutant by 0.1, 1 and 10 μm IAA. Surprisingly, ABP1 was itself an early auxin-up-regulated gene. IAA uptake into the mutant seedlings during auxin treatments was indistinguishable from wild-type. Basipetal auxin transport in young roots was slower in the mutant, indicating a PIN2/EIR1 defect, while acropetal transport was indistinguishable from wild-type. In the eir1 background, three of the early auxin-regulated genes tested (IAA2, IAA13 and ABP1) were more strongly induced by 1 μm IAA in comparison to wild-type, but eight of them were less up-regulated in comparison to wild-type. Similar but not identical disturbances in regulation of early auxin-regulated genes indicate tight functional linkage of ABP1 and auxin transport regulation. We hypothesize that ABP1 is involved in the regulation of polar auxin transport, and thus affects local auxin concentration and early auxin gene regulation. In turn, ABP1 itself is under the transcriptional control of auxin.

Sophisticated routing of ships is increasingly recognised as an important contribution to safe, reliable and economical ship operation. The more reliable the weather forecasts and the performance simulation of ships in a seaway become, the better they serve to identify the best possible route in terms of criteria like estimated time of arrival (ETA), fuel consumption (FUEL), safety (of ship, crew, passengers and cargo) and comfort. This establishes a multi-objective, non-linear and constrained optimisation problem in which a suitable compromise has to be found between opposing targets. For its solution, a new optimisation approach to select the most advantageous route on the basis of hydrodynamic simulations and sophisticated weather forecasts is posed. Transfer functions are employed to assess the operating behaviour of a ship in waves. Probabilistic ensemble forecasts are applied to account for the stochastic behaviour of weather. A multi-objective genetic algorithm turns out to be a suitable optimisati...

Background. Recipient presensitization represents a major hurdle to successful renal transplantation. Previous case series have suggested that the proteasome inhibitor bortezomib directly affects the alloantibody-secreting plasma cells in rejecting allograft recipients. However, the ability of this agent to desensitize nonimmunosuppressed transplant candidates before transplantation is currently unknown. Methods. In this analysis, two sensitized hemodialysis patients were selected to receive two subsequent bortezomib cycles. Bortezomib was given at 1.3 mg/m2 on days 1, 4, 8, and 11. Dexamethasone was added to the second cycle to enhance treatment efficiency. Serial immune monitoring included cytotoxic panel reactive antibody testing, Luminex single antigen testing for anti-human leukocyte antigen (HLA) IgG with or without C4d-fixing capability, and ABO antibody detection. Results. During a half-year follow-up period, cytotoxic panel reactive antibody decreased from 87% to 80% (patient 1) and 37% to 13% (patient 2). Patient 1 showed a 40% reduction in binding intensities of identified Luminex HLA single antigen reactivities and, in parallel, slight reductions in ABO blood group antibody and total immunoglobulin levels. In patient 2, bortezomib did not affect circulating antibody levels in a meaningful way. Both patients showed a more than 50% reduction in the levels of anti-HLA antibody-triggered C4d deposition to Luminex beads. Conclusion. Our initial experience suggests that, without additional immunosuppressive measures, bortezomib has modest effects on circulating antibodies against HLA or blood group antigens. The reduced levels of antibody-triggered complement fixation, however, imply potential clinical relevance of proteasome inhibition for recipient desensitization.

Phospholipase A enzymes cleave phospho- and galactolipids to generate free fatty acids and lysolipids that function in animal and plant hormone signaling. Here, we describe three Arabidopsis patatin-related phospholipase A (pPLA) genes AtPLAIVA, AtPLAIVB, and AtPLAIVC and their corresponding proteins. Loss-of-function mutants reveal roles for these pPLAs in roots during normal development and under phosphate deprivation. AtPLAIVA is expressed strongly and exclusively in roots and AtplaIVA-null mutants have reduced lateral root development, characteristic of an impaired auxin response. By contrast, AtPLAIVB is expressed weakly in roots, cotyledons, and leaves but is transcriptionally induced by auxin, although AtplaIVB mutants develop normally. AtPLAIVC is expressed in the floral gynaecium and is induced by abscisic acid (ABA) or phosphate deficiency in roots. While an AtplaIVC-1 loss-of-function mutant displays ABA responsiveness, it exhibits an impaired response to phosphate deficiency during root development. Recombinant AtPLA proteins hydrolyze preferentially galactolipids and, less efficiently, phospholipids, although these enzymes are not localized in chloroplasts. We find that AtPLAIVA and AtPLAIVB are phosphorylated by calcium-dependent protein kinases in vitro and this enhances their activities on phosphatidylcholine but not on phosphatidylglycerol. Taken together, the data reveal novel functions of pPLAs in root development with individual roles at the interface between phosphate deficiency and auxin signaling.

For seakeeping model tests and the experimental investigation of offshore operations the water depth is a parameter which is difficult to adjust to a particular problem and scale. It poses a limit for the feasibility of model tests by governing the model scale—especially in small testing facilities. Therefore, it is often desirable to violate or ignore the condition “water depth” and to use larger models in order to carry out tests at higher Reynolds numbers. In this paper its influence is examined in order to clarify how it affects wave kinematics, wave forces, and wave–structure interaction, and where the deep water assumption holds. After a short recapitulation of the water wave theory, a freak wave sequence is presented that has been reproduced at two different wave tanks at scales 1:75 and 1:81 and two water depths. The wave kinematics are approximated with asymmetric high order Stokes waves. The comparison of the computational wave kinematics reveals that moderate water depths are of low importance for extreme waves with identical surface elevations but different water depths. In order to examine the effects regarding wave–structure interaction with regard to seakeeping investigations model tests are conducted at various water depths using the huge semi-submersible crane vessel Thialf. Here, the effect on heave and pitch motion is investigated. The model tests are accompanied by numerical calculations utilizing the panel code WAMIT. A comparison of the hydrodynamic coefficients in deep water with those in decreasing water depths is shown including coupling effects taking into account viscous damping which is determined in experiments. It is shown that for the given scale of 1:75 a water depth of 1 m is sufficient to model deep water conditions.

ABO-incompatible kidney transplantation is a promising strategy for enlargement of living-donor pools. In recent years, recipient desensitization by blood group antigen-specific immunoadsorption, together with rituximab and intravenous immunoglobulin, has allowed excellent graft performance after ABO-incompatible transplantation. Adopting this protocol, originally described by Tyden and coworkers, we performed four living-donor renal transplants across the ABO barrier (A1-->0, A1-->B, B-->A1, A2-->0) between July 2007 and August 2008. Recipients were aged 25-66 years, donors 49-69 years. A protocol of on-demand immunoadsorption was followed, based on serial post-transplant antibody monitoring. Substantial and sustained decrease of blood group antibody levels was achieved in all four recipients, therefore post-transplant immunoadsorption was not needed. Graft and patient survival after 4-18 months' follow-up was 100%. Current serum creatinine was 1.3-2.0 mg/dl. Two grafts showed C4d deposits in peritubular capillaries in the complete absence of typical morphological features of antibody-mediated rejection. One recipient experienced early graft dysfunction, diagnosed as Banff borderline lesion, which responded well to steroid pulse therapy. The same recipient developed de novo interstitial fibrosis/tubular atrophy and arteriolar hyalinosis, presumably the result of suboptimal control of blood pressure and/or calcineurin inhibitor therapy. Two of the four recipients developed lymphoceles necessitating surgical revision. Apart from urinary tract infection in three patients and subclinical CMV in one, no major infectious complications were reported. Notably, two stable recipients developed polyoma BK viremia without clinical or morphological manifestations of polyomavirus-associated nephropathy. The results obtained in our small series support the earlier reported high efficiency of desensitization based on antigen-specific immunoadsorption. Nevertheless, the lack of long-term data will necessitate continuous and prudent consideration of the benefits and risks of this strategy.

Spatial orders such as the Morton (Z) order, U-order, or X-order have applications in matrix manipulation, graphic rendering and data encryption. It is shown that these spatial orders are single examples of entire classes of spatial orders which can be defined in arbitrary numbers of dimensions and base values. Secondly, an algorithm is proposed which can be used to transform between these spatial orders and Cartesian coordinates. It is shown that the efficiency of the algorithm improves with a larger base value. By choosing a base value that corresponds to the available memory page size, the computational effort required to perform operations such as matrix multiplication can be optimized.

Background: Validations of routinely used serological typing methods require intense performance evaluations typically including large numbers of samples before routine application. However, such evaluations could be improved considering information about the frequency of standard blood groups and their variants. Meth-ods: Using RHDand ABOpopulation genetic data, a Caucasian-specific donor panel was compiled for a performance comparison of the three RhD and ABO serological typing methods MDmulticard (Medion Diagnostics), ID-System (DiaMed) and ScanGel (Bio-Rad). The final test panel included standard and variant RHDand ABOgenotypes, e.g. RhD categories, partial and weak RhDs, RhD DELs, and ABOsamples, mainly to interpret weak serological reactivity for blood group A specificity. All samples were from individuals recorded in our local DNA blood group typing database. Results: For ‘standard’ blood groups, results of performance were clearly interpretable for all three serological methods compared. However, when focusing on specific variant phenotypes, pronounced differences in reaction strengths and specificities were observed between them. Conclusions: A genetically and ethnically predefined donor test panel consisting of 93 individual samples only, delivered highly significant results for serological performance comparisons. Such small panels offer impressive representative powers, higher as such based on statistical chances and large numbers only.

Capillary C4d deposition is a valuable marker of antibody-mediated rejection (AMR). In this analysis, flow cytometric detection of alloantibody-triggered C4d deposition to HLA antigen-coated microparticles ([C4d]FlowPRA) was evaluated for its value as a marker for C4d deposition in renal allografts. For comparative analysis, 105 first renal biopsies performed for graft dysfunction and an equal number of concurrent sera were subjected to immunohistochemistry and [C4d] plus standard [IgG]FlowPRA, respectively. C4d deposition/fixation was detected in 17 biopsies and, applying [C4d]FlowPRA HLA class I and II screening, also in a small number of corresponding sera (N = 20). IgG reactivity detected by standard [IgG]FlowPRA was more frequent (49% of sera). Comparing [C4d]FlowPRA screening with capillary C4d staining, we found a high level of specificity (0.92 [95% confidence interval: 0.86-0.98]), which far exceeded that calculated for [IgG]FlowPRA (0.60 [0.50-0.70]). [IgG]FlowPRA screening, however, turned out to be superior in terms of sensitivity (0.94 [0.83-1.05] vs. 0.76 [0.56-0.97] calculated for C4d-fixing panel reactivity). Remarkably, posttransplant single antigen testing for identification of complement-fixing donor-specific alloreactivities failed to improve the predictive value of FlowPRA-based serology. In conclusion, our results suggest that detection of complement-fixing HLA panel reactivity could provide a specific tool for monitoring of C4d-positive AMR.

ABP1 and TIR1/AFBs are known as auxin receptors. ABP1 is linked to auxin responses several of which are faster than 10 min. TIR1 regulates auxin-induced transcription of early auxin genes also within minutes. We use transcription of such TIR1-dependent genes as indicator of TIR1 activity to show the rapid regulation of TIR1 by exogenous auxin. To this end, we used quantification of transcription of a set of fifteen early auxin-induced reporter genes at t = 10 and t = 30 min to measure this as a TIR1-dependent auxin response. We conducted this study in 22 mutants of auxin transporters (pin5, abcb1, abcb19, and aux1/lax3), protein kinases and phosphatases (ibr5, npr1, cpk3, CPK3-OX, d6pk1, d6pkl1-1, d6pkl3-2, d6pkl1-1/d6pkl2-2, and d6pkl1-1/d6pkl3-2), of fatty acid metabolism (fad2-1, fad6-1, ssi2, lacs4, lacs9, and lacs4/lacs9) and receptors (tir1, tir1/afb2, and tir1/afb3) and compared them to the wild type. After 10 min auxin application, in 18 out of 22 mutants mis-regulated expression of at least one reporter was found, and in 15 mutants transcription of two-to-three out of five selected auxin reporter genes was mis-regulated. After 30 min of auxin application to mutant plants, mis-regulation of reporter genes ranged from one to 13 out of 15 tested reporter genes. Those genes chosen as mutants were themselves not regulated in their expression by auxin for at least 1 h, excluding an influence of TIR1/AFBs on their transcription. The expression of TIR1/AFB genes was also not modulated by auxin for up to 3 h. Together, this excludes a feedback or feedforward of these mutant genes/proteins on TIR1/AFBs output of transcription in this auxin-induced response. However, an auxin-induced response needed an as yet unknown auxin receptor. We suggest that the auxin receptor necessary for the fast auxin-induced transcription modulation could be, instead, ABP1. The alternative hypothesis would be that auxin-induced expression of a protein, initiated by TIR1/AFBs receptors, could initiate these responses and that this unknown protein regulated TIR1/AFB activities within 10 min.

Summary Multidrug resistant pathogens are a widespread problem in the hospital setting especially on intensive care units (ICU). This study evaluated the susceptibility of clinical isolates of gramnegative extensively drug resistant organisms (XDR), methicillinresistant Staphylococcus aureus (MRSA), and vancomycin-resistant Enterococcus (VRE) to a proprietary chlorhexidine digluconate (CHG) formulation used in one brand of CHG-impregnated cloths. Ten isolates each of XDR Pseudomonas aeruginosa, XDR Acinetobacter baumannii, XDR Klebsiella pneumoniae, XDR Escherichia coli, MRSA, and vancomycin-resistant Enterococcus faecium from our hospital were tested. All isolates were susceptible to the proprietary CHG formulation (0.5%, 1%, 2%), with 99% to 100% suppression of growth at the earliest time point in time kill assays (1 minute for gram-positive and 15 seconds for gram-negative organisms). Minimum inhibitory concentrations ranged from 1 : 4096 to 1 : 65536 for MRSA, 1 : 1024 to 1 : 2048 for VRE, 1 : 2048 to 1 : 4096 for XDR E. coli, 1 : 512 to 1 : 2048 for XDR A. baumannii, 1 : 512 to 1 : 1024 for XDR P. aeruginosa, and 1 : 512 to 1 : 1024 for XDR K. pneumoniae. Cloths impregnated with this CHG formulation provide effective protection against colonization and infection by many pathogens. This study provides in vitro evidence that the proprietary CHG formulation used in one brand of CHG-impregnated cloths is effective against XDR gram-negative organisms, MRSA, and VRE.

BACKGROUND: Besides ABO and RH, the KEL blood group system, including the two antithetical antigens KEL1 and KEL2, is the most important owing to the frequent appearance of anti-KEL alloantibodies and their considerable clinical significance. So far, only limited information was available on KEL variant alleles determining the rare silent KELnull and KELel phenotypes with absent or diminished KEL antigen expression detected only by adsorption-elution techniques, respectively. STUDY DESIGN AND METHODS: For a systematic investigation of the KELnull and KELel phenotypes, 401 KEL:1,-2 samples (representing 2.6% of all Austrian KEL:1,-2 samples) and 811 KEL:1,2 samples were genotyped for the KEL*1/KEL*2-specific single-nucleotide polymorphism. All heterozygous KEL*1/KEL*2 and 4 additional KELnull samples were subjected to detailed immunohematologic examination and allele-specific sequencing. RESULTS: In 14 KEL:1,-2 samples, discrepant KEL*1/KEL*2 heterozygosity was observed, indicating the presence of silent or barely expressed KEL*2 alleles, whereas all KEL:1,2 individuals were homozygous for KEL*2. In the course of further molecular analysis, 8 novel KEL*2null and 2 KEL*2el alleles were discovered, representing 67 and 33 percent of previously known KEL*2null- and KEL*2el-encoding alleles, respectively. In addition, two different known KEL*2null and KEL*2el alleles each were confirmed. The immunohematologic properties of KEL variant red blood cells were defined by extended KEL phenotyping and flow cytometric KEL1, KEL2, KEL4, and KEL7 antigen as well as total Kell protein quantification. CONCLUSION: For the first time, exact KELnull and KELel population frequencies could be established in this population.

This longitudinal study investigated the effects of a multidisciplinary rehabilitation programme on postural stability in patients with low back pain. While the consequences of such rehabilitation programme have been described for pain, mobility, strength, and functional disability, the effects on postural stability have not been examined so far.Thirty-four patients suffering from chronic low back pain were included to participate in a multidisciplinary rehabilitation programme. We assessed postural stability, pain, strength of the lumbar extensor muscles, and functional disability. The examinations were performed before the intervention, after 20 training sessions ("half-way point"), and at the end of the rehabilitation programme.All outcome measures improved significantly from baseline to the first follow-up evaluation and remained constant until completion of the rehabilitation programme.A multidisciplinary outpatient rehabilitation programme may improve postural stability, muscle strength, pain, and functional disability in patients with chronic low back pain.

Space-filling curves have been found useful for many applications in diverse fields. A space-filling curve is a path in a 2 r ×2 r raster domain, which visits each location exactly once. In mathematical terms, space-filling curves linearize a 2D integer space, bijectively mapping the space to the integer line. An algorithm is presented, which generates a large number of space-filling curves/spatial orders. Functions are derived such that the code of each location can be calculated from its coordinates and, conversely, a location code can be decoded to yield the coordinates. The algorithm first generates generate 4×4 spatial orders; they subsequently may be scaled up to any desired domain of size 2 r × 2 r . The underlying theory of the algorithm, the processes for scaling up, encoding, and decoding are described in detail. The curves are generated as a set of incongruent curves, followed, if required, by the sets of associated congruent curves. A number of space-filling curves are illustrated.