Differential expression of liver fluke β-tubulin isotypes at selected life cycle stages

We have shown that Fasciola hepatica expresses at least six ß-tubulins in the adult stage of its life cycle, designated F.hep-ß-tub1-6 (Ryan et al., 2008). Here we show that different complements of tubulin isotypes are expressed in different tissues and at different life cycle stages; this information may inform the search for novel anthelmintics. The predominant (as judged by quantitative PCR) isotype transcribed at the adult stage was F.hep-ß-tub1 and immunolocalisation studies revealed that this isotype occurred mainly in mature spermatozoa and vitelline follicles. Quantitative PCR indicated that changes occurred in the transcription levels of ß-tubulin isotypes at certain life cycle stages and may be of importance in the efficacy of benzimidazole-based anthelmintic drugs, but there were no significant differences between the triclabendazole (TCBZ)-susceptible Leon isolate and the TCBZ-resistant Oberon isolate in the transcription levels of each of the isotypes. When three well-characterised isolates with differing susceptibilities to TCBZ were compared, only one amino acid change resulting from a homozygous coding sequence difference (Gly269Ser) in isotype 4 was observed. However, this change was not predicted to alter the overall structure of the protein. In conclusion, these findings indicate that there is tissue-specific expression of tubulin isotypes in the liver fluke but the development of resistance to TCBZ is not associated with changes in its presumed target molecule.

Long-term mass balance of perennial firn and ice in an Alpine cave (Austria):Constraints from radiocarbon-dated wood fragments

Hundsalm ice cave located at 1520 m altitude in a karst region of western Austria contains up to 7-m-thick deposits of snow, firn and congelation ice. Wood fragments exposed in the lower parts of an ice and firn wall were radiocarbon accelerator mass spectrometry (AMS) dated. Although the local stratigraphy is complex, the 19 individual dates - the largest currently available radiocarbon dataset for an Alpine ice cave - allow to place constraints on the accumulation and ablation history of the cave ice. Most of the cave was either ice free or contained only a small firn and ice body during the 'Roman Warm Period'; dates of three wood fragments mark the onset of firn and ice build-up in the 6th and 7th century ad. In the central part of the cave, the oldest samples date back to the 13th century and record ice growth coeval with the onset of the 'Little Ice Age'. The majority of the ice and firn deposit, albeit compromised by a disturbed stratigraphy, appears to have been formed during the subsequent centuries, supported by wood samples from the 15th to the 17th century. The oldest wood remains found so far inside the ice is from the end of the Bronze Age and implies that local relics of prehistoric ice may be preserved in this cave. The wood record from Hundsalm ice cave shows parallels to the Alpine glacier history of the last three millennia, for example, the lack of preserved wood remains during periods of known glacier minima, and underscores the potential of firn and ice in karst cavities as a long-term palaeoclimate archive, which has been degrading at an alarming rate in recent years. © The Author(s) 2013.

Transmission Potential of Rift Valley Fever virus over the course of the 2010 epidemic in South Africa

A Rift Valley fever (RVF) epidemic affecting animals on domestic livestock farms was reported in South Africa during January-August 2010. The first cases occurred after heavy rainfall, and the virus subsequently spread countrywide. To determine the possible effect of environmental conditions and vaccination on RVF virus transmissibility, we estimated the effective reproduction number (R) for the virus over the course of the epidemic by extending the Wallinga and Teunis algorithm with spatial information. Re reached its highest value in mid-February and fell below unity around mid-March, when vaccination coverage was 7.5%-45.7% and vector-suitable environmental conditions were maintained. The epidemic fade-out likely resulted first from the immunization of animals following natural infection or vaccination. The decline in vector-suitable environmental conditions from April onwards and further vaccination helped maintain R below unity. Increased availability of vaccine use data would enable evaluation of the effect of RVF vaccination campaigns.

Towards optimal clinical and epidemiological registration of haematological malignancies: Guidelines for recording progressions, transformations and multiple diagnoses

Haematological malignancies (HM) represent over 6% of the total cancer incidence in Europe and affect all ages, ranging between 45% of all cancers in children and 7% in the elderly. Thirty per cent of childhood cancer deaths are due to HM, 8% in the elderly. Their registration presents specific challenges, mainly because HM may transform or progress in the course of the disease into other types of HM. In the context of cancer registration decisions have to be made about classifying subsequent notifications on the same patient as the same tumour (progression), a transformation or a new tumour registration. Allocation of incidence date and method of diagnosis must also be standardised. We developed European Network of Cancer Registries (ENCR) recommendations providing specific advice for cancer registries to use haematology and molecular laboratories as data sources, conserve the original date of incidence in case of change of diagnosis, make provision for recording both the original as well as transformed tumour and to apply precise rules for recording and counting multiple diagnoses. A reference table advising on codes which reflect a potential transformation or a new tumour is included. This work will help to improve comparability of data produced by population-based cancer registries, which are indispensable for aetiological research, health care planning and clinical research, an increasing important area with the application of targeted therapies.

Holistic design of 8-way combining transformers in SiGe technology for use in millimetre-wave power amplifiers

This paper presents the design of a novel 8-way power-combining transformer for use in mm-wave power amplifier (PA). The combiner exhibits a record low insertion loss of 1.25 dB at 83.5 GHz. A complete circuit comprised of a power splitter, two-stage cascode PA array, a power combiner and input/output matching elements was designed and realized in SiGe technology. Measured gain of at least 16.8 dB was obtained from 76.4 GHz to 85.3 GHz with a peak 19.5 dB at 83 GHz. The prototype delivered 12.5 dBm OP and 14 dBm saturated output power when operated from a 3.2 V DC supply voltage at 78 GHz. © 2013 IEEE.

Modification of Fluorescent Photoinduced Electron Transfer (PET) Sensors/Switches To Produce Molecular Photo-Ionic Triode Action

The fluorophore-spacer₁-receptor₁-spacer₂-receptor₂ system (where receptor₂ alone is photoredox-inactive) shows ionically tunable proton-induced fluorescence off-on switching, which is reminiscent of thermionic triode behavior. This also represents a new extension to modular switch systems based on photoinduced electron transfer (PET) towards the emulation of analogue electronic devices.

Tools for Finding Inconsistencies in Real-world Logic-based Systems

Currently there is extensive theoretical work on inconsistencies in logic-based systems. Recently, algorithms for identifying inconsistent clauses in a single conjunctive formula have demonstrated that practical application of this work is possible. However, these algorithms have not been extended for full knowledge base systems and have not been applied to real-world knowledge. To address these issues, we propose a new algorithm for finding the inconsistencies in a knowledge base using existing algorithms for finding inconsistent clauses in a formula. An implementation of this algorithm is then presented as an automated tool for finding inconsistencies in a knowledge base and measuring the inconsistency of formulae. Finally, we look at a case study of a network security rule set for exploit detection (QRadar) and suggest how these automated tools can be applied.

Predictors and dynamics of postpartum relapses in women with multiple sclerosis

Several studies have shown that pregnancy reduces multiple sclerosis (MS) relapses, which increase in the early postpartum period. Postpartum relapse risk has been predicted by pre-pregnancy disease activity in some studies.

Survival for haematological malignancies in Europe between 1997 and 2008 by region and age: results of EUROCARE-5, a population-based study

Background: More effective treatments have become available for haematological malignancies from the early 2000s, but few large-scale population-based studies have investigated their effect on survival. Using EUROCARE data, and HAEMACARE morphological groupings, we aimed to estimate time trends in population-based survival for 11 lymphoid and myeloid malignancies in 20 European countries, by region and age. Methods: In this retrospective observational study, we included patients (aged 15 years and older) diagnosed with haematological malignancies, diagnosed up to Dec 31, 2007, and followed up to Dec 31, 2008. We used data from the 30 cancer registries (across 20 countries) that provided continuous incidence and good quality data from 1992 to 2007. We used a hybrid approach to estimate age-standardised and age-specific 5-year relative survival, for each malignancy, overall and for five regions (UK, and northern, central, southern, and eastern Europe), and four 3-year periods (1997–99, 2000–02, 2003–05, 2006–08). For each malignancy, we also estimated the relative excess risk of death during the 5 years after diagnosis, by period, age, and region. Findings: We analysed 560 444 cases. From 1997–99 to 2006–08 survival increased for most malignancies: the largest increases were for diffuse large B-cell lymphoma (42·0% [95% CI 40·7–43·4] to 55·4% [54·6–56·2], p<0·0001), follicular lymphoma (58·9% [57·3–60·6] to 74·3% [72·9–75·5], p<0·0001), chronic myeloid leukaemia (32·3% [30·6–33·9] to 54·4% [52·5–56·2], p<0·0001), and acute promyelocytic leukaemia (50·1% [43·7–56·2] to 61·9% [57·0–66·4], p=0·0038, estimate not age-standardised). Other survival increases were seen for Hodgkin's lymphoma (75·1% [74·1–76·0] to 79·3% [78·4–80·1], p<0·0001), chronic lymphocytic leukaemia/small lymphocytic lymphoma (66·1% [65·1–67·1] to 69·0% [68·1–69·8], p<0·0001), multiple myeloma/plasmacytoma (29·8% [29·0–30·6] to 39·6% [38·8–40·3], p<0·0001), precursor lymphoblastic leukaemia/lymphoma (29·8% [27·7–32·0] to 41·1% [39·0–43·1], p<0·0001), acute myeloid leukaemia (excluding acute promyelocytic leukaemia, 12·6% [11·9–13·3] to 14·8% [14·2–15·4], p<0·0001), and other myeloproliferative neoplasms (excluding chronic myeloid leukaemia, 70·3% [68·7–71·8] to 74·9% [73·8–75·9], p<0·0001). Survival increased slightly in southern Europe, more in the UK, and conspicuously in northern, central, and eastern Europe. However, eastern European survival was lower than that for other regions. Survival decreased with advancing age, and increased with time only slightly in patients aged 75 years or older, although a 10% increase in survival occurred in elderly patients with follicular lymphoma, diffuse large B-cell lymphoma, and chronic myeloid leukaemia. Interpretation: These trends are encouraging. Widespread use of new and more effective treatment probably explains much of the increased survival. However, the persistent differences in survival across Europe suggest variations in the quality of care and availability of the new treatments. High-resolution studies that collect data about stage at diagnosis and treatments for representative samples of cases could provide further evidence of treatment effectiveness and explain geographic variations in survival.

Herschel key program HERITAGE:A far-infrared source catalog for the Magellanic Clouds

Observations from the HERschel Inventory of the Agents of Galaxy Evolution (HERITAGE ) have been used to identify dusty populations of sources in the Large and Small Magellanic Clouds (LMC and SMC). We conducted the study using the HERITAGE catalogs of point sources available from the Herschel Science Center from both the Photodetector Array Camera and Spectrometer (PACS; 100 and 160 μm) and Spectral and Photometric Imaging Receiver (SPIRE; 250, 350, and 500 μm) cameras. These catalogs are matched to each other to create a Herschel band-merged catalog and then further matched to archival Spitzer IRAC and MIPS catalogs from the Spitzer Surveying the Agents of Galaxy Evolution (SAGE) and SAGE-SMC surveys to create single mid- to far-infrared (far-IR) point source catalogs that span the wavelength range from 3.6 to 500 μm. There are 35,322 unique sources in the LMC and 7503 in the SMC. To be bright in the FIR, a source must be very dusty, and so the sources in the HERITAGE catalogs represent the dustiest populations of sources. The brightest HERITAGE sources are dominated by young stellar objects (YSOs), and the dimmest by background galaxies. We identify the sources most likely to be background galaxies by first considering their morphology (distant galaxies are point-like at the resolution of Herschel) and then comparing the flux distribution to that of the Herschel Astrophysical Terahertz Large Area Survey (ATLAS ) survey of galaxies. We find a total of 9745 background galaxy candidates in the LMC HERITAGE images and 5111 in the SMC images, in agreement with the number predicted by extrapolating from the ATLAS flux distribution. The majority of the Magellanic Cloud-residing sources are either very young, embedded forming stars or dusty clumps of the interstellar medium. Using the presence of 24 μm emission as a tracer of star formation, we identify 3518 YSO candidates in the LMC and 663 in the SMC. There are far fewer far-IR bright YSOs in the SMC than the LMC due to both the SMC's smaller size and its lower dust content. The YSO candidate lists may be contaminated at low flux levels by background galaxies, and so we differentiate between sources with a high ("probable") and moderate ("possible ") likelihood of being a YSO. There are 2493/425 probable YSO candidates in the LMC/SMC. Approximately 73% of the Herschel YSO candidates are newly identified in the LMC, and 35% in the SMC. We further identify a small population of dusty objects in the late stages of stellar evolution including extreme and post-asymptotic giant branch, planetary nebulae, and supernova remnants. These populations are identified by matching the HERITAGE catalogs to lists of previously identified objects in the literature. Approximately half of the LMC sources and one quarter of the SMC sources are too faint to obtain accurate ample FIR photometry and are unclassified.

Defining the role of common variation in the genomic and biological architecture of adult human height

Using genome-wide data from 253,288 individuals, we identified 697 variants at genome-wide significance that together explained one-fifth of the heritability for adult height. By testing different numbers of variants in independent studies, we show that the most strongly associated 1/42,000, 1/43,700 and 1/49,500 SNPs explained 1/421%, 1/424% and 1/429% of phenotypic variance. Furthermore, all common variants together captured 60% of heritability. The 697 variants clustered in 423 loci were enriched for genes, pathways and tissue types known to be involved in growth and together implicated genes and pathways not highlighted in earlier efforts, such as signaling by fibroblast growth factors, WNT/I 2-catenin and chondroitin sulfate-related genes. We identified several genes and pathways not previously connected with human skeletal growth, including mTOR, osteoglycin and binding of hyaluronic acid. Our results indicate a genetic architecture for human height that is characterized by a very large but finite number (thousands) of causal variants.

The PREDICTS database: a global database of how local terrestrial biodiversity responds to human impacts

Biodiversity continues to decline in the face of increasing anthropogenic pressures such as habitat destruction, exploitation, pollution and introduction of alien species. Existing global databases of species' threat status or population time series are dominated by charismatic species. The collation of datasets with broad taxonomic and biogeographic extents, and that support computation of a range of biodiversity indicators, is necessary to enable better understanding of historical declines and to project - and avert - future declines. We describe and assess a new database of more than 1.6 million samples from 78 countries representing over 28,000 species, collated from existing spatial comparisons of local-scale biodiversity exposed to different intensities and types of anthropogenic pressures, from terrestrial sites around the world. The database contains measurements taken in 208 (of 814) ecoregions, 13 (of 14) biomes, 25 (of 35) biodiversity hotspots and 16 (of 17) megadiverse countries. The database contains more than 1% of the total number of all species described, and more than 1% of the described species within many taxonomic groups - including flowering plants, gymnosperms, birds, mammals, reptiles, amphibians, beetles, lepidopterans and hymenopterans. The dataset, which is still being added to, is therefore already considerably larger and more representative than those used by previous quantitative models of biodiversity trends and responses. The database is being assembled as part of the PREDICTS project (Projecting Responses of Ecological Diversity In Changing Terrestrial Systems - http://www.predicts.org.uk). We make site-level summary data available alongside this article. The full database will be publicly available in 2015.

Scales and Hierarchies: A Cross-Disciplinary Perspective

The volume advances our understanding of the role of scales and hierarchies across the linguistic sciences. Although scales and hierarchies are widely assumed to play a role in the modelling of linguistic phenomena, their status remains controversial, and it is these controversies that the present volume tackles head-on.