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Lipids contribute to hematopoiesis and membrane properties and dynamics, however, little is known about the role of lipids in megakaryopoiesis. Here, a lipidomic analysis of megakaryocyte progenitors, megakaryocytes, and platelets revealed a unique lipidome progressively enriched in polyunsaturated fatty acid (PUFA)-containing phospholipids. In vitro, inhibition of both exogenous fatty acid functionalization and uptake and de novo lipogenesis impaired megakaryocyte differentiation and proplatelet production. In vivo, mice on a high saturated fatty acid diet had significantly lower platelet counts, which was prevented by eating a PUFA-enriched diet. Fatty acid uptake was largely dependent on CD36, and its deletion in mice resulted in thrombocytopenia. Moreover, patients with a CD36 loss-of-function mutation exhibited thrombocytopenia and increased bleeding. Our results suggest that fatty acid uptake and regulation is essential for megakaryocyte maturation and platelet production, and that changes in dietary fatty acids may be a novel and viable target to modulate platelet counts.

Food supplements in Europe are subject to food safety legislation. They should not be confused with pharmaceuticals. Rather, they are foods, whose purpose is to supplement the normal diet, and represent concentrated sources of nutrients (i. e. vitamins and minerals, including trace elements) or other substances with a nutritional or physiological effect. Nevertheless, it should be kept in mind that consumers may in some cases use food supplements for the purpose of self-medication. In the context of anamnesis, physicians should specifically question their patients about the use of food supplements. This can be of significant relevance for evaluation of possible undesirable or adverse effects, influences on laboratory parameters, or interactions with pharmaceuticals, which may be due to consumption of certain products that are marketed as food supplements. Furthermore, education of patients with respect to the possible benefits and risks related to the use of vitamins, minerals and other constituents of food supplements should be intensified.

In vielen Regionen der Welt werden Insekten von Menschen verspeist. Sie werden dort zumeist als ganze Insekten nach traditionellen Zubereitungen wie z.B. Kochen, Braten, Rosten, Grillen, Rauchern, Frittieren, Salzen, Wurzen, Marinieren und Trocknen, verzehrt. In Europa hingegen ist der Verzehr von Insekten wenig verbreitet. Als Futtermittel fur Nutztiere sind Insekten aufgrund der Regelungen zum Verfutterungsverbot fur tierische Proteine zum Schutz vor TSE-Erkrankungen (Verordnung (EG) Nr. 999/2001) aktuell nicht zulassig. Aufgrund der vielfach postulierten effizienten Produktionsmoglichkeiten und der gunstigen Nahrstoffzusammensetzung von Insekten beginnt auch in Europa eine offentliche Diskussion vor allem uber die Moglichkeiten einer industriellen Zucht und Verarbeitung von Insekten als Lebens- und Futtermittel. Zwar gibt es dort, wo Insekten traditionell verzehrt werden, Alltagserfahrungen mit der Verarbeitung, Lagerung und Zubereitung von meist der Natur entnommenen Insekten, jedoch fehlt wissenschaftlich fundiertes Wissen im Bereich der technologischen Aufbereitungs- und Verarbeitungsschritte, vor allem aber auch im Hinblick auf Sicherheitsaspekte im Zusammenhang mit der industriellen Produktion von Insekten. Zur Diskussion dieser Fragen kamen mehr als 200 Interessierte aus Forschung und Wissenschaft, der Politik und von Behorden, der Lebensmitteluberwachung, sowie aus Verbraucherschutz- und Wirtschaftsverbanden zu einem wissenschaftlichen Symposium am BfR zusammen (Abb. 1). Das Symposium bot einen Uberblick uber die gesamte Thematik von der Regulation, Haltung und Zucht von Insekten, Sicherheitsaspekten bis hin zu ethischen Fragen sowie der Verbraucherwahrnehmung. Hierfur konnten Referentinnen und Referenten aus Forschung und Wissenschaft sowie aus internationalen Institutionen und regulatorischen Behorden gewonnen werden. Wahrend der abschliesenden Podiumsdiskussion wurden unterschiedliche Standpunkte aus Forschung, Wirtschaft und Verbraucherschutzorganisationen zu den moglichen Chancen und Risiken aber auch zu regulatorischen Aspekten erortert. Open image in new window Abb.1 „Insekten als Lebens- oder Futtermittel - Nahrung der Zukunft?“ - Zur Diskussion dieser Frage kamen Vertreter aus Forschung und Wissenschaft, der Politik und von Behorden, der Lebensmitteluberwachung, sowie aus Verbraucherschutzverbanden und Verbanden der Wirtschaftsbeteiligten zu einem wissenschaftlichen Symposium zusammen

Food supplements in Europe are subject to food safety legislation. They should not be confused with pharmaceuticals. Rather, they are foods, whose purpose is to supplement the normal diet, and represent concentrated sources of nutrients (i. e. vitamins and minerals, including trace elements) or other substances with a nutritional or physiological effect. Nevertheless, it should be kept in mind that consumers may in some cases use food supplements for the purpose of self-medication. In the context of anamnesis, physicians should specifically question their patients about the use of food supplements. This can be of significant relevance for evaluation of possible undesirable or adverse effects, influences on laboratory parameters, or interactions with pharmaceuticals, which may be due to consumption of certain products that are marketed as food supplements. Furthermore, education of patients with respect to the possible benefits and risks related to the use of vitamins, minerals and other constituents of food supplements should be intensified.

Introduction and Objectives Benralizumab is an anti-eosinophilic monoclonal antibody that improves daily symptoms for patients with severe, uncontrolled asthma with eosinophilic inflammation. This study evaluated the association of asthma symptom improvements with activity function and health-related quality of life assessments. Methods Pooled analyses of two Phase III benralizumab trials (NCT01928771, NCT01914757) of adult patients with severe asthma (1474 benralizumab, 742 placebo) who received high-dosage inhaled corticosteroids/long-acting β2-agonists were conducted. Daily asthma symptoms (daytime and night-time symptoms), daily activity function (activity limitations, activity avoidance, need to pace oneself during activities), feeling stress, feeling tired, rescue medication use, night-time awakenings, Asthma Control Questionnaire, 6-question version (ACQ-6), and Standardised Asthma Quality of Life Questionnaire for patients 12 years and older (AQLQ[S]+12) were captured with an electronic diary. Daily assessments were summarised as biweekly means. Spearman’s rank correlation coefficient was used to examine the association of daily asthma symptoms with other aforementioned diary items and with forced expiratory volume in 1 s (FEV1). Associations of Results Associations were observed between asthma symptoms and daily activity function items, daily stress, ACQ-6, AQLQ(S)+12 overall and domain scores, and FEV1 at baseline and change from baseline to end of treatment in both benralizumab and placebo arms (table). Strong correlations were observed between daily symptoms and daily assessments of activity function items (r=0.66–0.77), feeling tired (r=0.66–0.76), and ACQ-6 scores (r=0.58–0.68) at baseline and change from baseline to end of treatment. Moderate correlations were observed between symptom scores and feeling stressed (r=0.36–0.50); rescue medication use (r=0.49–0.57); and AQLQ(S)+12 overall and symptoms, activity limitation, and emotional domains (r=−0.41–0.62). Although a very weak correlation between symptom improvement and FEV1 was expected, benralizumab-treated patients had a better correlation between symptom improvement and FEV1 improvement compared with placebo (r=−0.21 vs. −0.13), possibly because of substantial FEV1 improvement observed in benralizumab-treated patients. Conclusions Asthma-related symptoms and improvements are associated with other important aspects of improvement in patient well-being, especially for patients uncontrolled on optimal care.

In the late 1930s, it was discovered that liver and yeast extracts can be used to correct certain cases of megaloblastic anemia in pregnancy. The factor responsible for this was isolated from spinach leaves in the 1940s, and referred to as folate, a term derived from the Latin word folium for leaf. Folate is considered an essential nutrient for human beings. Folic acid, the synthetic form of the vitamin, is used in dietary supplements, medicines and fortified foods. Since the 1980s, it has been recommended that women who plan to become pregnant and pregnant women during the first trimester of pregnancy take folic acid supplements. This recommendation was based on studies that revealed that periconceptional folic acid supplementation can reduce the risk for neural tube defects (NTDs). Many countries later implemented folic acid fortification programs. The resulting population-wide increase of folic acid intakes led to significant reductions in NTD rates. However, a temporarily increased colorectal cancer incidence has been reported to coincide with the fortification programs in the USA and Canada. On the basis of currently available data from experimental and human studies it can be concluded that the association between folate/folic acid and cancer is rather complex: Folate intake in the range of the dietary reference intake (DRI) is associated with a reduced risk for cancer in healthy populations, whereas high intakes of folic acid might result in an increased risk for cancer incidence or progression in persons with precancerous lesions and under certain conditions. Since no adverse effects have been observed in association with the intake of dietary folate, research activities that aim at investigating cause and effect relationships focus on folic acid.

Consumers are exposed to low concentrations of a variety of pesticide residues in or on food. Some of them might interfere with the endocrine system. While each individual active substance has been extensively tested for toxicity and safety, potential combination effects possibly resulting from combined exposure to different pesticides have seldomly been tested so far, especially in vivo. Since the adrenal gland is a key endocrine organ, we investigated if and how substances of a group of fungicides presumed to interfere with the biosynthesis of steroid hormones affect this organ when applied individually and in combination in a broad dose range. A 28 day feeding study was conducted in Wistar rats by using three (tri)azole fungicides considered to potentially affect the endocrine system (cyproconazole, epoxiconazole and prochloraz) individually at five dose levels, ranging from 0.9 ppm to 2400 ppm, and in combination at three dose levels. The parameters analysed included classical toxicology (pathology, histopathology, clinical chemistry) and molecular toxicology endpoints (gene expression arrays and quantitative real time PCR e.g. of Star, HSD3 beta, Cyp11a1, Cyp11b1, Cyp11b2, Cyp 21, ApoE), as well as hormone analysis. A dose-dependent decrease in the adrenal gland weight of rats treated with epoxiconazole alone, which was accompanied by an atrophy of the adrenal gland as well as by an increase in the serum cholesterol level and which only became statistically significant at the top dose levels, was observed. These effects were attenuated in the combination experiments, although the same epoxiconazole concentration was used.

Microfluidics technology has emerged as a powerful tool for the radiosynthesis of positron emission tomography (PET) and single-photon emission computed tomography radiolabeled compounds. In this work, we have exploited a continuous flow microfluidic system (Advion, Inc., USA) for the [(18) F]-fluorine radiolabeling of the malonic acid derivative, [(18) F] 2-(5-fluoro-pentyl)-2-methyl malonic acid ([(18) F]-FPMA), also known as [(18) F]-ML-10, a radiotracer proposed as a potential apoptosis PET imaging agent. The radiosynthesis was developed using a new tosylated precursor. Radiofluorination was initially optimized by manual synthesis and served as a basis to optimize reaction parameters for the microfluidic radiosynthesis. Under optimized conditions, radio-thin-layer chromatography analysis showed 79% [(18) F]-fluorine incorporation prior to hydrolysis and purification. Following hydrolysis, the [(18) F]-FPMA was purified by C18 Sep-Pak, and the final product was analyzed by radio-HPLC (high-performance liquid chromatography). This resulted in a decay-corrected 60% radiochemical yield and ≥98% radiochemical purity. Biodistribution data demonstrated rapid blood clearance with less than 2% of intact [(18) F]-FPMA radioactivity remaining in the circulation 60 min post-injection. Most organs showed low accumulation of the radiotracer, and radioactivity was predominately cleared through kidneys (95% in 1 h). Radio-HPLC analysis of plasma and urine samples showed a stable radiotracer at least up to 60 min post-injection.

Numerous food supplements contain phytochemical compounds as active ingredients. Although such supplements are often perceived by consumers as being risk-free, the safety of many of them is currently uncertain. The present review provides two examples for risk assessment for phytochemical ingredients that are used in certain supplements marketed for sportspeople-synephrine (extracted from fruits of Citrus aurantium) and hydroxycitric acid (HCA, isolated from fruits of Garcinia cambogia). Animal and human studies, as well as case reports, provide evidence for cardiovascular effects due to ingestion of high synephrine doses, especially in combination with caffeine and physical exertion. A dose of up to 6.7 mg synephrine/day, however, which is equivalent to the median dietary intake from conventional foods in Germany, is presumed to represent a safe intake from supplements. In subchronic animal studies, administration of high doses of certain HCA-containing preparations led to testicular toxicity (i.e., testicular atrophy and impaired spermatogenesis), yielding a no observed adverse effect level of 389 mg HCA/kg bw/day. In view of lack of adequate human data on the safety of HCA preparations, particularly with respect to the human male reproductive system, substantial uncertainties exist regarding the safety of supplements containing high amounts of HCA.

Histopathologic validation of a PET tracer requires assessment of colocalization of the tracer with its intended biologic target. Using thin tissue section autoradiography, it is possible to visualize the spatial distribution of the PET tracer uptake and compare it with the distribution of the intended biologic target (as visualized with immunohistochemistry). The purpose of this study was to develop and evaluate an objective methodology for deformable coregistration of autoradiography and microscopy images acquired from a set of sequential tissue sections.Tumor-bearing animals were injected with 3'-deoxy-3'-(18)F-fluorothymidine ((18)F-FLT), (14)C-FDG, and other markers of tumor microenvironment including Hoechst 33342 (blood-flow surrogate). After sacrifice, tumors were excised, frozen, and sectioned. Multiple stacks of sequential 8 μm sections were collected from each tumor. From each stack, the middle (reference) sections were used to obtain images of (18)F-FLT and (14)C-FDG uptake distributions using dual-tracer autoradiography. Sections adjacent to the reference were used to acquire all histopathologic data (e.g., images of cell proliferation, hematoxylin and eosin). Hoechst images were acquired from all sections. To correct for deformations and misalignments induced by tissue processing and image acquisition, the Hoechst image of each nonreference section was deformably registered to the reference Hoechst image. This transformation was then applied to all images acquired from the same tissue section. In this way, all microscopy images were registered to the reference Hoechst image. The Hoechst-to-autoradiography image registration was done using rigid point-set registration based on external markers visible in both images.The mean error of Hoechst to (18)F-FLT autoradiography registration (both images acquired from the same section) was 30.8 ± 20.1 μm. The error of Hoechst-based deformable registration of histopathologic images (acquired from sequential tissue sections) was 23.1 ± 17.9 μm. Total error of registration of autoradiography images to the histopathologic images acquired from adjacent sections was evaluated at 44.9 μm. This coregistration precision supersedes current rigid registration methods with reported errors of 100-200 μm.Deformable registration of autoradiography and histopathology images acquired from sequential sections is feasible and accurate when performed using corresponding Hoechst images.

There is growing concern that environmental substances with a potential to modulate the hormonal system may have harmful effects on human health. Consequently, a new EU regulation names endocrine disrupting properties as one of the cut-off criteria for the approval of plant protection products, although it currently fails to provide specific science-based measures for the assessment of substances with such properties. Since specific measures are to be presented by the European Commission in 2013 the development of assessment and decision criteria is a key challenge concerning the implementation of this new EU regulation. Proposals of such decision criteria for substances with potential endocrine disrupting properties in human health risk assessment were developed by the German Federal Institute for Risk Assessment (BfR) and discussed at an expert workshop in November 2009. Under consideration of the requirements laid down within the new plant protection product legislation and the scientific discussions during the workshop, a conceptual framework on evaluation of substances for endocrine disrupting properties in a regulatory context is presented in this paper. Central aspects of the framework include assessment of adversity of effects, establishment of a mode/mechanism of action in animals, considerations concerning the relevance of effects to humans and two options for a regulatory decision.

Introduction We investigated the effect of benralizumab, an interleukin-5 receptor alpha–directed cytolytic monoclonal antibody, on rescue medication use by patients with severe, uncontrolled asthma with eosinophilic inflammation. Methods We analyzed pooled data from two Phase III studies, SIROCCO (NCT01928771; 48 weeks [N=1,204]) and CALIMA (NCT01914757; 56 weeks [N=1,306]). Patients aged 12–75 years with severe, uncontrolled asthma, ≥2 exacerbations in the year before enrollment, and blood eosinophil counts ≥300 cells/μL were evaluated. Patients received benralizumab 30 mg every 8 weeks (Q8W; first three doses every 4 weeks) or placebo with their existing high-dosage inhaled corticosteroids and long-acting β2-agonists. Daily, daytime, and night-time rescue medication use and night-time awakenings requiring rescue medication use were evaluated at Day 1, Day 3, Day 7, and at end of treatment. Results By Day 3 with benralizumab Q8W, reductions in daily and night-time rescue medication use and in night-time awakenings requiring rescue medication use were observed for patients with blood eosinophil counts ≥300 cells/μL. Reductions in daytime rescue medication use were obtained by Day 7 (all nominal prequiring rescue medication use relative to baseline compared with patients receiving placebo (all nominal p≤0.013) (table). Conclusions Benralizumab Q8W reduced daily rescue medication use by patients with severe, uncontrolled asthma with eosinophilic inflammation as early as Day 3, and treatment effects were sustained until end of treatment.

Multidrug resistance (MDR) is a cause of treatment failure in many cancer patients. MDR refers to a phenotype whereby a tumor is resistant to a large number of natural chemotherapeutic drugs. Having prior knowledge of the presence of such resistance would decrease morbidity from unsuccessful therapy and allow for the selection of individuals who may benefit from the coadministration of MDR-inhibiting drugs. The Tc-99m-labeled single-photon-emitting radiotracers sestamibi and tetrofosmin have shown some predictive value. However, positron-emitting radiotracers, which allow for dynamic quantitative imaging, hold promise for a more accurate and specific identification of MDRtumors.MDR-expressing tumors are resistant to paclitaxel, which is commonly used as a chemotherapeutic agent. 4-[18F]Fluoropaclitaxel (FPAC) is a PET-radiolabeled analogue of paclitaxel. Preclinical studies have shown the uptake of FPAC to be inversely proportional to tumor MDR expression. FPAC PET imaging in normal volunteers shows biodistribution to be similar to that in nonhuman primates. Imaging in a breast cancer patient showed FPAC localization in a primary tumor that responded to chemotherapy, while failure to localize in mediastinal disease corresponded with only partial response.FPAC PET imaging shows promise for the noninvasive pretreatment identification of MDR-expressing tumors. While much additional work is needed, this work represents a step toward image-guided personalized medicine.

A positron-emitting paclitaxel (PAC) derivative could allow in vivo measurement of multidrug resistance in tumors and, therefore, predict a potential chemotherapeutic benefit to patients. [18F]Paclitaxel was produced using a 2-reaction vessel automated synthesizer followed by HPLC purification. Optimized reaction conditions resulted in radiochemical yields of 21.2+/-9.6% at end of bombardment, radiochemical purity >99%, and specific activity of 159+/-43 G Bq/micromol. [18F]Paclitaxel activities of 1.33+/-0.729 G Bq (n=7) were obtained in sterile, pyrogen-free solution for IV administration.

The serotonin receptor type 3 is a pentameric ligand-gated ion channel regulating intestinal motility, nausea, and vomiting in humans. The HTR3B gene codes for the subunit B of this receptor. The HTR3B transcription start site is not unequivocally identified. In the present study we used transcription start site analyses, transcript-specific RT-PCR, and functional promoter analyses to identify the 5' structure of the HTR3B gene. According to these experiments, two alternative promoters control the expression of different HTR3B transcripts in the peripheral and central nervous system. The transcription start sites observed in the intestine corresponded to the current human genome annotation (NCBI Build 36.1, March 2006). The transcription start sites in the brain, however, were localized in a region about 4000 bp downstream. The brain transcripts lacked the coding first exon of the HTR3B structure published earlier but had an upstream-extended exon 2 containing a new potential translational start site. Reporter gene analyses showed significant promoter activity of the genomic region located 1560 bp upstream to 93 bp downstream of the brain-specific transcription start sites. This data suggests a different transcriptional regulation of the HTR3B gene in the peripheral and the central nervous system that leads to the expression of transcripts with variations in the 5' coding sequence. Further studies on the expression, structure and function of therefore expected tissue-specific 5-HT(3B) isoforms are required.

Leberschaden sind eine haufige Komplikation einer medikamentosen Therapie. Ihre Diagnose ist schwierig und meist nur als Ausschlussdiagnose zu stellen, da medikamentos-toxische Leberschaden fast alle Formen einer Hepatopathie imitieren konnen. Morphologisch werden je nach der betroffenen Zielzelle akute und chronische Leberschaden vom hepatitischen Typ, eine Granulombildung und Verfettung, eine akute oder chronische cholestatische Schadigung in Form einer reinen Cholestase, einer Cholestase mit Entzundung oder gemischte Schaden unterschieden. Eine Fibrose kann bei jeder Schadigung als portale Fibrose oder als perisinusoidale Fibrose auftreten. Vaskulare Schaden oder Neubildungen sind selten. Den Veranderungen liegt haufiger ein nichtvorhersehbarer und im Tierexperiment nicht nachzuvollziehender Typ-B-Schaden als ein aus Toxizitatsstudien bekannter Typ-A-Schaden vor. Da es keine spezifische Therapie gibt, sind eine fruhzeitige Erkennung und das Absetzen des Medikaments notwendig.

Chronic myeloid leukemia (CML) relapse after allogeneic stem cell transplantation (SCT) is a relatively frequent situation, which is correlated to disease status, time from diagnosis to transplant and T-cell depletion. We evaluated the potential for early minimal residual disease (MRD) BCR-ABL quantification to predict relapse of CML patients receiving allogeneic SCT. Minimal residual disease was analyzed by real-time quantitative reverse transcriptase-polymerase chain reaction (RQ-PCR) at day 100 (d100) in 38 patients with >1 year follow-up after conventional non-T-cell-depleted SCT. Normal ABL control values from 1724 follow-up blood samples were used to define an RQ-PCR amplifiability index and the limits of reliable use of BCR-ABL ratios. We then compared the 14 patients with a high-level d100 BCR-ABL/ABL ratio (> or = 10(-4)) to that of the 24 patients with a negative/low-level ratio (

Potential forest growth predicted by the Physiological Principles in Predicting Growth (3-PG) model was compared for forest and deforested areas in the Legal Amazon to assess potential differing regeneration associated with climate. Historical deforestation and regeneration have occurred in environmentally marginal areas that influence regional carbon sequestration estimates. Effects of El Niño–induced drought further reduce simulated production by decreasing soil water availability in areas with shallow soils and high transpiration potential. The model was calibrated through comparison of literature biomass and with satellite-based estimates. Net primary productivity (NPP) for mature Amazonian forests from the 3-PG model was positively correlated (r 2 = 0.77) with a Moderate Resolution Imaging Spectroradiometer (MODIS)-derived algorithm, though with some bias. Annual total NPP for the study area using a 1961–90 average climatology was 4.6 Pg C yr−1, which decreased to 4.2 Pg C yr−1 when simulated with climate from the severe 1997/98 El Niño event. From a regional analysis, results showed that biomass accumulation is almost entirely controlled by the availability of soil water. Also, areas currently forested in the eastern Amazon are more sensitive to extreme El Niño–induced drought than southern areas with the greatest deforestation extent.

Determining the phylogenetic relationships among the major lines of angiosperms is a long-standing problem, yet the uncertainty as to the phylogenetic affinity of these lines persists. While a number of studies have suggested that the ANITA (Amborella-Nymphaeales-Illiciales-Trimeniales-Aristolochiales) grade is basal within angiosperms, studies of complete chloroplast genome sequences also suggested an alternative tree, wherein the line leading to the grasses branches first among the angiosperms. To improve taxon sampling in the existing chloroplast genome data, we sequenced the chloroplast genome of the monocot Acorus calamus. We generated a concatenated alignment (89,436 positions for 15 taxa), encompassing almost all sequences usable for phylogeny reconstruction within spermatophytes. The data still contain support for both the ANITA-basal and grasses-basal hypotheses. Using simulations we can show that were the ANITA-basal hypothesis true, parsimony (and distance-based methods with many models) would be expected to fail to recover it. The self-evident explanation for this failure appears to be a long-branch attraction (LBA) between the clade of grasses and the out-group. However, this LBA cannot explain the discrepancies observed between tree topology recovered using the maximum likelihood (ML) method and the topologies recovered using the parsimony and distance-based methods when grasses are deleted. Furthermore, the fact that neither maximum parsimony nor distance methods consistently recover the ML tree, when according to the simulations they would be expected to, when the out-group (Pinus) is deleted, suggests that either the generating tree is not correct or the best symmetric model is misspecified (or both). We demonstrate that the tree recovered under ML is extremely sensitive to model specification and that the best symmetric model is misspecified. Hence, we remain agnostic regarding phylogenetic relationships among basal angiosperm lineages.

Adenokarzinoide sind seltene Tumoren mit histologischen Merkmalen sowohl von Karzinoiden, als auch von Adenokarzinomen. Sie besitzen ein aggressiveres biologisches Verhalten als klassische Karzinoide. Wir berichten uber eine 64-jahrige Patientin mit einer diffusen Infiltration der Appendixwand durch ein Adenokarzinoid. Aufgrund des Befalls des chirurgischen Absetzungsrandes und der Tumorausbreitung wurde eine Hemikolektomie durchgefuhrt. Es existieren keine eindeutigen Kriterien, welche die operative Wahl zwischen Appendektomie und Hemikolektomie vorschreiben. Es wird vermutet, dass bei kleinen Tumoren in der Appendixspitze die alleinige Appendektomie ausreichend ist. Patienten mit einer diffusen Appendixbeteiligung bedurfen einer aggressiveren chirurgischen Intervention.

We developed a process-based model of forest growth, carbon cycling and land-cover dynamics named CARLUC (for CARbon and Land-Use Change) to estimate the size of terrestrial carbon pools in terra firme (nonflooded) forests across the Brazilian Legal Amazon and the net flux of carbon resulting from forest disturbance and forest recovery from disturbance. Our goal in building the model was to construct a relatively simple ecosystem model that would respond to soil and climatic heterogeneity that allows us to study the impact of Amazonian deforestation, selective logging and accidental fire on the global carbon cycle. This paper focuses on the net flux caused by deforestation and forest re-growth over the period from 1970 to 1998. We calculate that the net flux to the atmosphere during this period reached a maximum of � 0.35PgCyr � 1 (1PgC 5 1 � 10 15 gC) in 1990, with a cumulative release of � 7PgC from 1970 to 1998. The net flux is higher than predicted by an earlier study (Houghton et al., 2000) by a total of 1PgC over the period 1989‐1998 mainly because CARLUC predicts relatively high mature forest carbon storage compared with the datasets used in the earlier study. Incorporating the dynamics of litter and soil carbon pools into the model increases the cumulative net flux by � 1PgC from 1970 to 1998, while different assumptions about land-cover dynamics only caused small changes. The uncertainty of the net flux, calculated with a Monte-Carlo approach, is roughly 35% of the mean value (1SD).

Angiosperms (flowering plants) dominate contemporary terrestrial flora with roughly 250,000 species, but their origin and early evolution are still poorly understood. In recent years, molecular evidence has accumulated suggesting a dicotyledonous origin of monocots. Phylogenetic reconstructions have suggested that several dicotyledonous groups that include taxa such as Amborella, Austrobaileya, and Nymphaea branch off as the most basal among angiosperms. This has led to the concept of monocots, "eudicots," "basal dicots," and "ANITA" groupings. Here, we present the sequence and phylogenetic analyses of the chloroplast DNA of Nymphaea alba. Phylogenetic analyses of our 14-species data set, consisting of 29,991 aligned nucleotide positions per chloroplast genome, revealed consistent support for Nymphaea being a divergent member of a monophyletic dicot assemblage. Three distinct angiosperm lineages were supported in the majority of our phylogenetic analyses-eudicots, Magnoliopsida, and monocots. However, the monocot lineage leading to the grasses was the deepest branching. Although analyses of only one individual gene alignment (out of 61) is consistent with some recently proposed hypotheses for the paraphyly of dicots, we also report observations that nine genes do not support paraphyly of dicots. Instead, they support the basal monocot-dicot split. Consistent with this finding, we also report observations suggesting that the monocot lineage leading to the grasses has the strongest phylogenetic affinity to gymnosperms. Our findings have general implications for studies of substitution model specification and analyses of concatenated genome data.