Serologic vaccination response after solid organ transplantation: a systematic review

BACKGROUND Infectious diseases after solid organ transplantation (SOT) are one of the major complications in transplantation medicine. Vaccination-based prevention is desirable, but data on the response to active vaccination after SOT are conflicting. METHODS In this systematic review, we identify the serologic response rate of SOT recipients to post-transplantation vaccination against tetanus, diphtheria, polio, hepatitis A and B, influenza, Streptococcus pneumoniae, Haemophilus influenzae, Neisseria meningitides, tick-borne encephalitis, rabies, varicella, mumps, measles, and rubella. RESULTS Of the 2478 papers initially identified, 72 were included in the final review. The most important findings are that (1) most clinical trials conducted and published over more than 30 years have all been small and highly heterogeneous regarding trial design, patient cohorts selected, patient inclusion criteria, dosing and vaccination schemes, follow up periods and outcomes assessed, (2) the individual vaccines investigated have been studied predominately only in one group of SOT recipients, i.e. tetanus, diphtheria and polio in RTX recipients, hepatitis A exclusively in adult LTX recipients and mumps, measles and rubella in paediatric LTX recipients, (3) SOT recipients mount an immune response which is for most vaccines lower than in healthy controls. The degree to which this response is impaired varies with the type of vaccine, age and organ transplanted and (4) for some vaccines antibodies decline rapidly. CONCLUSION Vaccine-based prevention of infectious diseases is far from satisfactory in SOT recipients. Despite the large number of vaccination studies preformed over the past decades, knowledge on vaccination response is still limited. Even though the protection, which can be achieved in SOT recipients through vaccination, appears encouraging on the basis of available data, current vaccination guidelines and recommendations for post-SOT recipients remain poorly supported by evidence. There is an urgent need to conduct appropriately powered vaccination trials in well-defined SOT recipient cohorts.

Falkland Island English

This chapter examines some of the grammatical variability and non-standardness found in the English of the Falkland Islands. The Falklands are an archipelago of over 700 islands located in the western South Atlantic Ocean, 480km off the east coast of Argentina. Although the population is small – around 3000 - the islands cover an area of over 12000km2 – slightly larger than Jamaica and half the size of Wales, making them, after Greenland, the most sparsely populated political entity in the world. In political terms, the Falklands are an Overseas Territory of the United Kingdom. In contrast to the rural isolated image that the Falklands perhaps conjure up, the community is, in demographic terms, an urban and diverse one. Over 85% of the population living in the capital Stanley. The 2006 census (Government of the Falkland Islands 2007: 6) shows that 55% of the population were not born on the Islands, with the largest migrant groups coming from the UK, St Helena (another British Overseas Territory, located in the eastern South Atlantic), Chile and Australia. It also highlighted the fact that people born in 62 different countries were resident on the islands at the time (Pascoe and Pepper 2008: 38). By way of a comparison, only Monaco and Andorra, in Europe, have a higher proportion of their populations made up of migrants. In addition to the local Falkland population, there is a large military presence on the islands at the Royal Airforce Base at Mount Pleasant, 50km south-west of Stanley. The Head of State is the monarch of the UK, who is represented on the islands by a governor. The democratically elected 11-member Legislative Assembly is responsible for day-to-day government of the islands. The Falklands are perhaps most famous because of their 74 day occupation by Argentina in 1982. It is not appropriate here to go into detail about the dispute between the UK and Argentina about the sovereignty of the Islands. What is undisputed is that there has been a continuous Anglophone speech community on the islands since the early 1830s, making it one of the most recently developed ‘Inner Circle’ (Kachru 1985) Englishes in the world. This chapter examines the grammatical characteristics of Falkland Island English, drawn from a transcribed corpus of over 500,000 words of informal conversational speech, collected by Andrea Sudbury both in Stanley and in ‘Camp’ (the local name for the rest of the islands) (see Sudbury 2000, 2001 for more details about the methods used in the survey).

Evidence that the novel receptor FGFRL1 signals indirectly via FGFR1

Fibroblast growth factor (FGF) receptor-like protein 1 (FGFRL1) is a recently discovered member of the FGF receptor (FGFR) family. Similar to the classical FGFRs, it contains three extracellular immunoglobulin-like domains and interacts with FGF ligands. However, in contrast to the classical receptors, it does not contain any intracellular tyrosine kinase domain and consequently cannot signal by transphosphorylation. In mouse kidneys, FgfrL1 is expressed primarily at embryonic stages E14-E15 in regions where nascent nephrons develop. In this study, we used whole-mount in situ hybridization to show the spatial pattern of five different Fgfrs in the developing mouse kidney. We compared the expression pattern of FgfrL1 with that of other Fgfrs. The expression pattern of FgfrL1 closely resembled that of Fgfr1, but clearly differed from that of Fgfr2‑Fgfr4. It is therefore conceivable that FgfrL1 signals indirectly via Fgfr1. The mechanisms by which FgfrL1 affects the activity of Fgfr1 remain to be elucidated.

Eine neue Chronologie des 3. Jahrtausends v. Chr. Ergebnisse der ARCANE Final Conference

Das Projekt ARCANE zeigt der Archäologie der Alten Welt einen neuen methodischen Weg auf und revolutionierte zugleich die Chronologie des 3. Jts. v. Chr. Sechs Jahre lang hatten mehrere Arbeitsgruppen unter Hinzuziehung einer streng materialbezogenen Methodik an der Erstellung von Regionalchronologien gearbeitet, aus denen anschließend durch interregionale Verknüpfungen eine neue Chronologie für ein Gebiet entstand, das von der Ägäis im Westen bis zum Iran im Osten sowie vom Kaukasus im Norden bis zum Sinai im Süden reichte.

Serotyping of Toxoplasma gondii in cats (Felis domesticus) reveals predominance of type II infections in Germany.

BACKGROUND Cats are definitive hosts of Toxoplasma gondii and play an essential role in the epidemiology of this parasite. The study aims at clarifying whether cats are able to develop specific antibodies against different clonal types of T. gondii and to determine by serotyping the T. gondii clonal types prevailing in cats as intermediate hosts in Germany. METHODOLOGY To establish a peptide-microarray serotyping test, we identified 24 suitable peptides using serological T. gondii positive (n=21) and negative cat sera (n=52). To determine the clonal type-specific antibody response of cats in Germany, 86 field sera from T. gondii seropositive naturally infected cats were tested. In addition, we analyzed the antibody response in cats experimentally infected with non-canonical T. gondii types (n=7). FINDINGS Positive cat reference sera reacted predominantly with peptides harbouring amino acid sequences specific for the clonal T. gondii type the cats were infected with. When the array was applied to field sera from Germany, 98.8% (85/86) of naturally-infected cats recognized similar peptide patterns as T. gondii type II reference sera and showed the strongest reaction intensities with clonal type II-specific peptides. In addition, naturally infected cats recognized type II-specific peptides significantly more frequently than peptides of other type-specificities. Cats infected with non-canonical types showed the strongest reactivity with peptides presenting amino-acid sequences specific for both, type I and type III. CONCLUSIONS Cats are able to mount a clonal type-specific antibody response against T. gondii. Serotyping revealed for most seropositive field sera patterns resembling those observed after clonal type II-T. gondii infection. This finding is in accord with our previous results on the occurrence of T. gondii clonal types in oocysts shed by cats in Germany.

A tephrostratigraphic record for the last glacial-interglacial cycle from Lake Ohrid, Albania and Macedonia

ABSTRACT: Here we present a tephrostratigraphic record (core Co1202) recovered from the northeastern part of Lake Ohrid (Republics of Macedonia and Albania) reaching back to Marine Isotope Stage (MIS) 6. Overall ten horizons (OT0702-1 to OT0702-10) containing volcanic tephra have been recognised throughout the 14.94m long sediment succession. Four tephra layers were visible at macroscopic inspection (OT0702-4, OT0702-6, OT0702-8 and OT0702-9), while the remaining six are cryptotephras (OT0702-1, OT0702-2, OT0702-3, OT0702-5, OT0702-7 and OT0702-10) identified from peaks in K, Zr and Sr intensities, magnetic susceptibility measurements, and washing and sieving of the sediments. Glass shards of tephra layers and cryptotephras were analysed with respect to their major element composition, and correlated to explosive eruptions of Italian volcanoes. The stratigraphy and the major element composition of tephra layers and cryptotephras allowed the correlation of OT0702-1 to AD 472 or AD 512 eruptions of Somma-Vesuvius, OT0702-2 to the FL eruption of Mount Etna, OT0702-3 to the Mercato from Somma-Vesuvius, OT0702-4 to SMP1-e/Y-3 eruption from the Campi Flegrei caldera, OT0702-5 to the Codola eruption (Somma-Vesuvius or Campi Flegrei), OT0702-6 to the Campanian Ignimbrite/Y-5 from the Campi Flegrei caldera, OT0702- 7 to the Green Tuff/Y-6 eruption from Pantelleria Island, OT0702-8 to the X-5 eruption probably originating from the Campi Flegrei caldera, OT0702-9 to the X-6 eruption of generic Campanian origin, and OT0702-10 to the P-11 eruption from Pantelleria Island. The fairly well-known ages of these tephra layers and parent eruptions provide new data on the dispersal and deposition of these tephras and, furthermore, allow the establishment of a chronological framework for core Co1202 for a first interpretation of major sedimentological changes.

The craniosacral progression of muscle development influences the emergence of neuromuscular junction alterations in a severe murine model for spinal muscular atrophy.

AIMS As 4-day-old mice of the severe spinal muscular atrophy (SMA) model (dying at 5-8 days) display pronounced neuromuscular changes in the diaphragm but not the soleus muscle, we wanted to gain more insight into the relationship between muscle development and the emergence of pathological changes and additionally to analyse intercostal muscles which are affected in human SMA. METHODS Structures of muscle fibres and neuromuscular junctions (NMJs) of the diaphragm, intercostal and calf muscles of prenatal (E21) and postnatal (P0 and P4) healthy and SMA mice were analysed by light and transmission electron microscopy. NMJ innervation was studied by whole mount immunofluorescence in diaphragms of P4 mice. RESULTS During this period, the investigated muscles still show a significant neck-to-tail developmental gradient. The diaphragm and calf muscles are most and least advanced, respectively, with respect to muscle fibre fusion and differentiation. The number and depth of subsynaptic folds increases, and perisynaptic Schwann cells (PSCs) acquire a basal lamina on their outer surface. Subsynaptic folds are connected to an extensive network of tubules and beaded caveolae, reminiscent of the T system in adult muscle. Interestingly, intercostal muscles from P4 SMA mice show weaker pathological involvement (that is, vacuolization of PSCs and perineurial cells) than those previously described by us for the diaphragm, whereas calf muscles show no pathological changes. CONCLUSION SMA-related alterations appear to occur only when the muscles have reached a certain developmental maturity. Moreover, glial cells, in particular PSCs, play an important role in SMA pathogenesis.

Oxidative Stress in Hypobaric Hypoxia and Influence on Vessel-Tone Modifying Mediators

Increased pulmonary artery pressure is a well-known phenomenon of hypoxia and is seen in patients with chronic pulmonary diseases, and also in mountaineers on high altitude expedition. Different mediators are known to regulate pulmonary artery vessel tone. However, exact mechanisms are not fully understood and a multimodal process consisting of a whole panel of mediators is supposed to cause pulmonary artery vasoconstriction. We hypothesized that increased hypoxemia is associated with an increase in vasoconstrictive mediators and decrease of vasodilatators leading to a vasoconstrictive net effect. Furthermore, we suggested oxidative stress being partly involved in changement of these parameters. Oxygen saturation (Sao2) and clinical parameters were assessed in 34 volunteers before and during a Swiss research expedition to Mount Muztagh Ata (7549 m) in Western China. Blood samples were taken at four different sites up to an altitude of 6865 m. A mass spectrometry-based targeted metabolomic platform was used to detect multiple parameters, and revealed functional impairment of enzymes that require oxidation-sensitive cofactors. Specifically, the tetrahydrobiopterin (BH4)-dependent enzyme nitric oxide synthase (NOS) showed significantly lower activities (citrulline-to-arginine ratio decreased from baseline median 0.21 to 0.14 at 6265 m), indicating lower NO availability resulting in less vasodilatative activity. Correspondingly, an increase in systemic oxidative stress was found with a significant increase of the percentage of methionine sulfoxide from a median 6% under normoxic condition to a median level of 30% (p<0.001) in camp 1 at 5533 m. Furthermore, significant increase in vasoconstrictive mediators (e.g., tryptophan, serotonin, and peroxidation-sensitive lipids) were found. During ascent up to 6865 m, significant altitude-dependent changes in multiple vessel-tone modifying mediators with excess in vasoconstrictive metabolites could be demonstrated. These changes, as well as highly significant increase in systemic oxidative stress, may be predictive for increase in acute mountain sickness score and changes in Sao2.

A new sensitive method for the quantification of glyoxal and methylglyoxal in snow and ice by stir bar sorptive extraction and liquid desorption-HPLC-ESI-MS

In this study, the development of a new sensitive method for the analysis of alpha-dicarbonyls glyoxal (G) and methylglyoxal (MG) in environmental ice and snow is presented. Stir bar sorptive extraction with in situ derivatization and liquid desorption (SBSE-LD) was used for sample extraction, enrichment, and derivatization. Measurements were carried out using high-performance liquid chromatography coupled to electrospray ionization tandem mass spectrometry (HPLC-ESI-MS/MS). As part of the method development, SBSE-LD parameters such as extraction time, derivatization reagent, desorption time and solvent, and the effect of NaCl addition on the SBSE efficiency as well as measurement parameters of HPLC-ESI-MS/MS were evaluated. Calibration was performed in the range of 1–60 ng/mL using spiked ultrapure water samples, thus incorporating the complete SBSE and derivatization process. 4-Fluorobenzaldehyde was applied as internal standard. Inter-batch precision was <12 % RSD. Recoveries were determined by means of spiked snow samples and were 78.9 ± 5.6 % for G and 82.7 ± 7.5 % for MG, respectively. Instrumental detection limits of 0.242 and 0.213 ng/mL for G and MG were achieved using the multiple reaction monitoring mode. Relative detection limits referred to a sample volume of 15 mL were 0.016 ng/mL for G and 0.014 ng/mL for MG. The optimized method was applied for the analysis of snow samples from Mount Hohenpeissenberg (close to the Meteorological Observatory Hohenpeissenberg, Germany) and samples from an ice core from Upper Grenzgletscher (Monte Rosa massif, Switzerland). Resulting concentrations were 0.085–16.3 ng/mL for G and 0.126–3.6 ng/mL for MG. Concentrations of G and MG in snow were 1–2 orders of magnitude higher than in ice core samples. The described method represents a simple, green, and sensitive analytical approach to measure G and MG in aqueous environmental samples.

Forest structure and composition of previously selectively logged and non-logged montane forests at Mt. Kilimanjaro

The montane forests of Mount Kilimanjaro in Tanzania have been subjected to a long history of selective logging. However, since 1984 logging of indigenous trees is prohibited. Today, these forests allow us to evaluate the long-term effects of selective logging. We mapped the height and diameter at breast height (DBH) of all trees >10 cm DBH on 10 sites of 0.25 ha. Five sites represent non-logged forests, another five selectively logged forests. We tested whether forests were still visibly affected 30–40 years after selective logging in terms of their forest structure and tree diversity. Additionally we compared tree densities of different species guilds, including disturbance-indicator species, late-successional species and main timber species. Furthermore, we specifically compared the community size distributions of selectively logged and non-logged forests, first across all species and then for the most important timber species, Ocotea usambarensis, alone. 30–40 years after selective logging forests still showed a higher overall stem density, mainly due to higher relative abundances of small trees (<50 cm DBH) in general, and higher densities of small size class stems of late-successional species specifically. For O. usambarensis, the selectively logged sites harboured higher relative abundances of small trees and lower relative abundances of harvestable trees. The higher relative abundance of small O. usambarensis-stems in selectively logged forests appears promising for future forest recovery. Thus, outside protected areas, selective logging may be a sustainable management option if logging cycles are considerably longer than 40 years, enough large source trees remain, and the recruiting O. usambarensis individuals find open space for their establishment.

Ceramic foam plates: a new tool for processing fresh radical prostatectomy specimens

Procurement of fresh tissue of prostate cancer is critical for biobanking and generation of xenograft models as an important preclinical step towards new therapeutic strategies in advanced prostate cancer. However, handling of fresh radical prostatectomy specimens has been notoriously challenging given the distinctive physical properties of prostate tissue and the difficulty to identify cancer foci on gross examination. Here, we have developed a novel approach using ceramic foam plates for processing freshly cut whole mount sections from radical prostatectomy specimens without compromising further diagnostic assessment. Forty-nine radical prostatectomy specimens were processed and sectioned from the apex to the base in whole mount slices. Putative carcinoma foci were morphologically verified by frozen section analysis. The fresh whole mount slices were then laid between two ceramic foam plates and fixed overnight. To test tissue preservation after this procedure, formalin-fixed and paraffin-embedded whole mount sections were stained with hematoxylin and eosin (H&E) and analyzed by immunohistochemistry, fluorescence, and silver in situ hybridization (FISH and SISH, respectively). There were no morphological artifacts on H&E stained whole mount sections from slices that had been fixed between two plates of ceramic foam, and the histological architecture was fully retained. The quality of immunohistochemistry, FISH, and SISH was excellent. Fixing whole mount tissue slices between ceramic foam plates after frozen section examination is an excellent method for processing fresh radical prostatectomy specimens, allowing for a precise identification and collection of fresh tumor tissue without compromising further diagnostic analysis.

Multiple roles of complement MASP-1 at the interface of innate immune response and coagulation

MASP-1 is a versatile serine protease that cleaves a number of substrates in human blood. In recent years it became evident that besides playing a crucial role in complement activation MASP-1 also triggers other cascade systems and even cells to mount a more powerful innate immune response. In this review we summarize the latest discoveries about the diverse functions of this multi-faceted protease. Recent studies revealed that among MBL-associated serine proteases, MASP-1 is the one responsible for triggering the lectin pathway via its ability to rapidly autoactivate then cleave MASP-2, and possibly MASP-3. The crystal structure of MASP-1 explains its more relaxed substrate specificity compared to the related complement enzymes. Due to the relaxed specificity, MASP-1 interacts with the coagulation cascade and the kinin generating system, and it can also activate endothelial cells eliciting pro-inflammatory signaling.

Effects of ground semen collection on weight bearing on hindquarters, libido, and semen parameters in stallions

Collection of semen on the ground from the standing stallion represents an alternative method to dummy mount semen collection and is of increasing popularity for sport stallions, males suffering from health problems, or in studs without a dummy or suitable mare at disposal. Our aim was to collect and compare spermatological and physiological data associated with traditional and ground semen collection. Twelve of 23 Franches-Montagnes stallions were selected to carry out semen collection on a dummy and while standing in a crossed experimental protocol. Semen quantity and quality parameters, weight bearing on hindquarters, and behavioral and libido data were recorded. Ground versus dummy mount semen collection was accompanied by lower seminal volume (15.9 ± 14.6 vs. 22.0 ± 13.3 mL; P < 0.01) and lower total sperm count (4.913 ± 2.721 × 10(9) vs. 6.544 ± 2.856 × 10(9) sperm; P < 0.001). No significant differences were found concerning sperm motility and viability. Time to ejaculation was longer, and the number of attempts to ejaculation was higher (P = 0.053) in the standing position compared with the mount on the dummy. A higher (P < 0.01) amount of tail flagging was manifested by the stallions during ejaculation on the dummy compared to when standing. There was no difference in weight bearing on hindquarters when comparing dummy collection (51.2 ± 2.5%) and standing collection (48.9 ± 5.5%). Ground semen collection can be considered as a viable option for stallions that cannot mount a dummy or a mare. However, it requires training and may be not easily accepted by all stallions. Owners should be advised that ground semen collection is associated with significantly lower sperm numbers than with dummy mount semen collection.

SMARTnet: First Experience of Setting Up a Telescope System to Survey the Geostationary Ring

Space debris in geostationary orbits may be detected with optical telescopes when the objects are illuminated by the Sun. The advantage compared to Radar can be found in the illumination: radar illuminates the objects and thus the detection sensitivity depletest proportional to the fourth power of the d istance. The German Space Operation Center, GSOC, together with the Astronomical Institute of the University of Bern, AIUB, are setting up a telescope system called SMARTnet to demonstrate the capability of performing geostationary surveillance. Such a telescope system will consist of two telescopes on one mount: a smaller telescope with an aperture of 20cm will serve for fast survey while the larger one, a telescope with an aperture of 50cm, will be used for follow-up observations. The telescopes will be operated by GSOC from Oberpfaffenhofen by the internal monitoring and control system called SMARTnetMAC. The observation plan will be generated by MARTnetPlanning seven days in advance by applying an optimized planning scheduler, taking into account fault time like cloudy nights, priority of objects etc. From each picture taken, stars will be identified and everything not being a star is treated as a possible object. If the same object can be identified on multiple pictures within a short time span, the trace is called a tracklet. In the next step, several tracklets will be correlated to identify individual objects, ephemeris data for these objects are generated and catalogued . This will allow for services like collision avoidance to ensure safe operations for GSOC’s satellites. The complete data processing chain is handled by BACARDI, the backbone catalogue of relational debris information and is presented as a poster.

Photometric monitoring of non-resolved space debris and databases of optical light curves.

The population of space debris increased drastically during the last years. Collisions involving massive objects may produce large number of fragments leading to significantly growth of the space debris population. An effective remediation measure in order to stabilize the population in LEO, is therefore the removal of large, massive space debris. To remove these objects, not only precise orbits, but also more detailed information about their attitude states will be required. One important property of an object targeted for removal is its spin period and spin axis orientation. If we observe a rotating object, the observer sees different surface areas of the object which leads to changes in the measured intensity. Rotating objects will produce periodic brightness vari ations with frequencies which are related to the spin periods. Photometric monitoring is the real tool for remote diagnostics of the satellite rotation around its center of mass. This information is also useful, for example, in case of contingency. Moreover, it is also important to take into account the orientation of non-spherical body (e.g. space debris) in the numerical integration of its motion when a close approach with the another spacecr aft is predicted. We introduce the two databases of light curves: the AIUB data base, which contains about a thousand light curves of LEO, MEO and high-altitude debris objects (including a few functional objects) obtained over more than seven years, and the data base of the Astronomical Observatory of Odessa University (Ukraine), which contains the results of more than 10 years of photometric monitoring of functioning satellites and large space debris objects in low Earth orbit. AIUB used its 1m ZIMLAT telescope for all light curves. For tracking low-orbit satellites, the Astronomical Observatory of Odessa used the KT-50 telescope, which has an alt-azimuth mount and allows tracking objects moving at a high angular velocity. The diameter of the KT-50 main mirror is 0.5 m, and the focal length is 3 m. The Odessa's Atlas of light curves includes almost 5,5 thousand light curves for ~500 correlated objects from a time period of 2005-2014. The processing of light curves and the determination of the rotation period in the inertial frame is challenging. Extracted frequencies and reconstructed phases for some interesting targets, e.g. GLONASS satellites, for which also SLR data were available for confirmation, will be presented. The rotation of the Envisat satellite after its sudden failure will be analyzed. The deceleration of its rotation rate within 3 years is studied together with the attempt to determine the orientation of the rotation axis.