Apparent absence of Batrachochytrium salamandrivorans in wild urodeles in the United Kingdom

This is the final version. Available from the publisher via the DOI in this record.Whether an infectious disease threat to wildlife arises from pathogen introduction or the increased incidence of an already-present agent informs mitigation policy and actions. The prior absence of a pathogen can be difcult to establish, particularly in free-living wildlife. Subsequent to the epidemic emergence of the fungus, Batrachochytrium salamandrivorans (Bsal), in mainland Europe in 2010 and prior to its detection in captive amphibians in the United Kingdom (UK), we tested archived skin swabs using a Bsal-specifc qPCR. These samples had been collected in 2011 from 2409 wild newts from ponds across the UK. All swabs were negative for Bsal. Bayesian hierarchical modelling suggests that Bsal was absent from, or present at very low levels in, these ponds at the time of sampling. Additionally, surveillance of newt mortality incidents, 2013–2017, failed to detect Bsal. As this pathogen has been shown to be widespread in British captive amphibian collections, there is an urgent need to raise awareness of the importance of efective biosecurity measures, especially amongst people with captive amphibians, to help minimise the risk of Bsal spreading to the wild. Continued and heightened wild amphibian disease surveillance is a priority to provide an early warning system for potential incursion eventsDepartment for Environment, Food and Rural Affairs (DEFRA)Animal & Plant Health Agency (APHA

Effect of garlic on blood pressure: A systematic review and meta-analysis

The electronic version of this article is the complete one and can be found online at the publisher's website.Background: Non-pharmacological treatment options for hypertension have the potential to reduce the risk of cardiovascular disease at a population level. Animal studies have suggested that garlic reduces blood pressure, but primary studies in humans and non-systematic reviews have reported mixed results. With interest in complementary medicine for hypertension increasing, it is timely to update a systematic review and meta-analysis from 1994 of studies investigating the effect of garlic preparations on blood pressure. Methods: We searched the Medline and Embase databases for studies published between 1955 and October 2007. Randomised controlled trials with true placebo groups, using garlic-only preparations, and reporting mean systolic and/or diastolic blood pressure (SBP/DBP) and standard deviations were included in the meta-analysis. We also conducted subgroup meta-analysis by baseline blood pressure (hypertensive/normotensive), for the first time. Meta-regression analysis was performed to test the associations between blood pressure outcomes and duration of treatment, dosage, and blood pressure at start of treatment. Results: Eleven of 25 studies included in the systematic review were suitable for meta-analysis. Meta-analysis of all studies showed a mean decrease of 4.6 ± 2.8 mm Hg for SBP in the garlic group compared to placebo (n = 10; p = 0.001), while the mean decrease in the hypertensive subgroup was 8.4 ± 2.8 mm Hg for SBP (n = 4; p < 0.001), and 7.3 ± 1.5 mm Hg for DBP (n = 3; p < 0.001). Regression analysis revealed a significant association between blood pressure at the start of the intervention and the level of blood pressure reduction (SBP: R = 0.057; p = 0.03; DBP: R = -0.315; p = 0.02). Conclusion: Our meta-analysis suggests that garlic preparations are superior to placebo in reducing blood pressure in individuals with hypertension.Karin Ried, Oliver R. Frank, Nigel P. Stocks, Peter Fakler and Thomas Sulliva

Cancer mortality and morbidity among plutonium workers at the Sellafield plant of British Nuclear Fuels

The mortality of all 14 319 workers employed at the Sellafield plant of British Nuclear Fuels between 1947 and 1975 was studied up to the end of 1992, and cancer incidence was examined from 1971 to 1986, in relation to their exposures to plutonium and to external radiation. The cancer mortality rate was 5% lower than that of England and Wales and 3% less than that of Cumbria. The significant excesses of deaths from cancer of the pleura and thyroid found in an earlier study persist with further follow-up (14 observed, 4.0 expected for pleura; 6 observed, 2.2 expected for thyroid). All of the deaths from pleural cancer were among radiation workers. For neither site was there a significant association between the risk of the cancer and accumulated radiation dose. There were significant deficits of deaths from cancers of mouth and pharynx, liver and gall bladder, and larynx and leukaemia when compared with the national rates. Among all radiation workers, there was a significant positive association between accumulated external radiation dose and mortality from cancers of ill-defined and secondary sites (10-year lag, P = 0.04), leukaemia (no lag, P = 0.03; 2-year lag, P = 0.05), multiple myeloma (20-year lag, P = 0.02), all lymphatic and haematopoietic cancers (20-year lag, P = 0.03) and all causes of death combined (20-year lag, P = 0.008). Among plutonium workers, there were significant excesses of deaths from cancer of the breast (6 observed, 2.6 expected) and ill-defined and secondary cancers (29 observed, 20.1 expected). No significant positive trends were observed between the risk of deaths from cancers of any specific site, or all cancers combined, and cumulative plutonium and external radiation doses. For no cancer site was there a significant excess of cancer registrations compared with rates for England and Wales. Analysis of trends in cancer incidence showed significant increases in risk with cumulative plutonium plus external radiation doses for all lymphatic and haematopoietic neoplasms for 0-, 10- and 20-year lag periods. Taken as a whole, our findings do not suggest that workers at Sellafield who have been exposed to plutonium are at an overall significantly increased risk of cancer compared with other radiation workers. © 1999 Cancer Research Campaig

Mutation in utp15 Disrupts Vascular Patterning in a p53-Dependent Manner in Zebrafish Embryos

Angiogenesis is the process by which the highly branched and functional vasculature arises from the major vessels, providing developing tissues with nutrients, oxygen, and removing metabolic waste. During embryogenesis, vascular patterning is dependent on a tightly regulated balance between pro- and anti-angiogenic signals, and failure of angiogenesis leads to embryonic lethality. Using the zebrafish as a model organism, we sought to identify genes that influence normal vascular patterning.In a forward genetic screen, we identified mutant LA1908, which manifests massive apoptosis during early embryogenesis, abnormal expression of several markers of arterial-venous specification, delayed angiogenic sprouting of the intersegmental vessels (ISV), and malformation of the caudal vein plexus (CVP), indicating a critical role for LA1908 in cell survival and angiogenesis. Genetic mapping and sequencing identified a G to A transition in the splice site preceding exon 11 of utp15 in LA1908 mutant embryos. Overexpression of wild type utp15 mRNA suppresses all observed mutant phenotypes, demonstrating a causative relationship between utp15 and LA1908. Furthermore, we found that injecting morpholino oligonucleotides inhibiting p53 translation prevents cell death and rescues the vascular abnormalities, indicating that p53 is downstream of Utp15 deficiency in mediating the LA1908 phenotypes.Taken together, our data demonstrate an early embryonic effect of Utp15 deficiency on cell survival and the normal patterning of the vasculature and highlight an anti-angiogenic role of p53 in developing embryos

Multiple organism algorithm for finding ultraconserved elements

<p>Abstract</p> <p>Background</p> <p>Ultraconserved elements are nucleotide or protein sequences with 100% identity (no mismatches, insertions, or deletions) in the same organism or between two or more organisms. Studies indicate that these conserved regions are associated with micro RNAs, mRNA processing, development and transcription regulation. The identification and characterization of these elements among genomes is necessary for the further understanding of their functionality.</p> <p>Results</p> <p>We describe an algorithm and provide freely available software which can find all of the ultraconserved sequences between genomes of multiple organisms. Our algorithm takes a combinatorial approach that finds all sequences without requiring the genomes to be aligned. The algorithm is significantly faster than BLAST and is designed to handle very large genomes efficiently. We ran our algorithm on several large comparative analyses to evaluate its effectiveness; one compared 17 vertebrate genomes where we find 123 ultraconserved elements longer than 40 bps shared by all of the organisms, and another compared the human body louse, <it>Pediculus humanus humanus</it>, against itself and select insects to find thousands of non-coding, potentially functional sequences.</p> <p>Conclusion</p> <p>Whole genome comparative analysis for multiple organisms is both feasible and desirable in our search for biological knowledge. We argue that bioinformatic programs should be forward thinking by assuming analysis on multiple (and possibly large) genomes in the design and implementation of algorithms. Our algorithm shows how a compromise design with a trade-off of disk space versus memory space allows for efficient computation while only requiring modest computer resources, and at the same time providing benefits not available with other software.</p

Optically-guided frameless linac-based radiosurgery for brain metastases: clinical experience

The purpose of this study was to describe our clinical experience using optically-guided linear accelerator (linac)-based frameless stereotactic radiosurgery (SRS) for the treatment of brain metastases. Sixty-five patients (204 lesions) were treated between 2005 and 2008 with frameless SRS using an optically-guided bite-block system. Patients had a median of 2 lesions (range, 1–13). Prescription dose ranged from 14 to 22 Gy (median, 18 Gy) and was given in a single fraction. Clinical and radiographic evaluation occurred every 2–4 months following treatment. At a median follow-up of 6.2 months, actuarial survival at 12 months was 40% [95% confidence interval (CI), 28–52). Of 135 lesions that were evaluable for local control (LC), 119 lesions (88%) did not show evidence of progression. Actuarial 12 month LC was 76% (95% CI, 66–86). Tumors ≤2 cm in size had a better 12 month LC rate (81% vs. 36%, P = 0.017) than those >2 cm. Adverse events occurred in three patients (5%). Optically-guided linac-based frameless SRS can produce clinical outcomes that compare favorably to frame-based techniques. As this technique is convenient to use and allows for the uncomplicated delivery of hypofractionated radiotherapy, frameless SRS will likely have an increasingly important role in the management of brain metastases

No rapid audiovisual recalibration in adults on the autism spectrum

Autism spectrum disorders (ASD) are characterized by difficulties in social cognition, but are also associated with atypicalities in sensory and perceptual processing. Several groups have reported that autistic individuals show reduced integration of socially relevant audiovisual signals, which may contribute to the higher-order social and cognitive difficulties observed in autism. Here we use a newly devised technique to study instantaneous adaptation to audiovisual asynchrony in autism. Autistic and typical participants were presented with sequences of brief visual and auditory stimuli, varying in asynchrony over a wide range, from 512 ms auditory-lead to 512 ms auditory-lag, and judged whether they seemed to be synchronous. Typical adults showed strong adaptation effects, with trials proceeded by an auditory-lead needing more auditory-lead to seem simultaneous, and vice versa. However, autistic observers showed little or no adaptation, although their simultaneity curves were as narrow as the typical adults. This result supports recent Bayesian models that predict reduced adaptation effects in autism. As rapid audiovisual recalibration may be fundamental for the optimisation of speech comprehension, recalibration problems could render language processing more difficult in autistic individuals, hindering social communication

Next generation transcriptomes for next generation genomes using est2assembly

<p>Abstract</p> <p>Background</p> <p>The decreasing costs of capillary-based Sanger sequencing and next generation technologies, such as 454 pyrosequencing, have prompted an explosion of transcriptome projects in non-model species, where even shallow sequencing of transcriptomes can now be used to examine a range of research questions. This rapid growth in data has outstripped the ability of researchers working on non-model species to analyze and mine transcriptome data efficiently.</p> <p>Results</p> <p>Here we present a semi-automated platform '<it>est2assembly</it>' that processes raw sequence data from Sanger or 454 sequencing into a hybrid <it>de-novo </it>assembly, annotates it and produces GMOD compatible output, including a SeqFeature database suitable for GBrowse. Users are able to parameterize assembler variables, judge assembly quality and determine the optimal assembly for their specific needs. We used <it>est2assembly </it>to process <it>Drosophila </it>and <it>Bicyclus </it>public Sanger EST data and then compared them to published 454 data as well as eight new insect transcriptome collections.</p> <p>Conclusions</p> <p>Analysis of such a wide variety of data allows us to understand how these new technologies can assist EST project design. We determine that assembler parameterization is as essential as standardized methods to judge the output of ESTs projects. Further, even shallow sequencing using 454 produces sufficient data to be of wide use to the community. <it>est2assembly </it>is an important tool to assist manual curation for gene models, an important resource in their own right but especially for species which are due to acquire a genome project using Next Generation Sequencing.</p

The Personal and Health Service Impact of Falls in 85 Year Olds: Cross-Sectional Findings from the Newcastle 85+ Cohort Study

Falls are common in older people and increase in prevalence with advancing old age. There is limited knowledge about their impact in those aged 85 years and older, the fastest growing age group of the population. We investigated the prevalence and impact of falls, and the overlap between falls, dizziness and blackouts, in a population-based sample of 85 year olds.Cross-sectional analysis of baseline data from Newcastle 85+ Cohort Study.Primary care, North-East England.816 men and women aged 85 years.Structured interview with research nurse. Cost-consequence analysis of fall-related healthcare costs.Over 38% (313/816) of participants had fallen at least once in the previous 12 months and of these: 10.6% (33/312) sustained a fracture, 30.1% (94/312) attended an emergency department, and 12.8% (40/312) were admitted to hospital. Only 37.2% (115/309) of fallers had specifically discussed their falls problem with their general practitioner and only 12.7% (39/308) had seen a falls specialist. The average annual healthcare cost per faller was estimated at £202 (inter-quartile range £174-£231) or US$329 ($284-$377). 'Worry about falling' was experienced by 42.0% (128/305) of fallers, 'loss of confidence' by 40.0% (122/305), and 'going out less often' by 25.9% (79/305); each was significantly more common in women, odds ratios (95% confidence interval) for women: men of 2.63 (1.45-4.55), 4.00 (2.27-7.14), and 2.86 (1.54-5.56) respectively. Dizziness and blackouts were reported by 40.0% (318/796) and 6.4% (52/808) of participants respectively. There was marked overlap in the report of falls, dizziness and blackouts.Falls in 85 year olds are very common, associated with considerable psychological and physical morbidity, and have high impact on healthcare services. Wider use of fall prevention services is needed. Significant expansion in acute and preventative services is required in view of the rapid growth in this age group