Ambient vibration tests of a cross-laminated timber building

Cross-laminated timber has, in the last 6 years, been used for the first time to form shear walls and cores in multi-storey buildings of seven storeys or more. Such buildings can have low mass in comparison to conventional structural forms. This low mass means that, as cross-laminated timber is used for taller buildings still, their dynamic movement under wind load is likely to be a key design parameter. An understanding of dynamic lateral stiffness and damping, which has so far been insufficiently researched, will be vital to the effective design for wind-induced vibration. In this study, an ambient vibration method is used to identify the dynamic properties of a seven-storey cross-laminated timber building in situ. The random decrement method is used, along with the Ibrahim time domain method, to extract the modal properties of the structure from the acceleration measured under ambient conditions. The results show that this output-only modal analysis method can be used to extract modal information from such a building, and that information is compared with a simple structural model. Measurements on two occasions during construction show the effect of non-structural elements on the modal properties of the structure

A cost-effective method to quantify biological surface sediment reworking

We propose a simple and inexpensive method to determine the rate and pattern of surface sediment reworking by benthic organisms. Unlike many existing methods commonly used in bioturbation studies, which usually require sediment sampling, our approach is fully non-destructive and is well suited for investigating non-cohesive fine sediments in streams and rivers. Optical tracer (e.g., luminophores or coloured sand) disappearance or appearance is assessed through time based on optical quantification of surfaces occupied by tracers. Data are used to calculate surface sediment reworking (SSR) coefficients depicting bioturbation intensities. Using this method, we evaluated reworking activity of stream organisms (three benthic invertebrates and a fish) in laboratory microcosms mimicking pool habitats or directly in the field within arenas set in depositional zones. Our method was sensitive enough to measure SSR as low as 0.2 cm2.d-1, such as triggered by intermediate density (774 m-2) of Gammarus fossarum (Amphipoda) in microcosms. In contrast, complex invertebrate community in the field and a fish (Barbatula barabatula) in laboratory microcosms were found to yield to excessively high SSR (>60 cm2.d-1). Lastly, we suggest that images acquired during experiments can be used for qualitative evaluation of species-specific effects on sediment distribution

Impact of socioeconomic deprivation on rate and cause of death in severe mental illness

Background: Socioeconomic status has important associations with disease-specific mortality in the general population. Although individuals with Severe Mental Illnesses (SMI) experience significant premature mortality, the relationship between socioeconomic status and mortality in this group remains under investigated.<p></p> Aims: To assess the impact of socioeconomic status on rate and cause of death in individuals with SMI (schizophrenia and bipolar disorder) relative to the local (Glasgow) and wider (Scottish) populations.<p></p> Methods: Cause and age of death during 2006-2010 inclusive for individuals with schizophrenia or bipolar disorder registered on the Glasgow Psychosis Clinical Information System (PsyCIS) were obtained by linkage to the Scottish General Register Office (GRO). Rate and cause of death by socioeconomic status, measured by Scottish Index of Multiple Deprivation (SIMD), were compared to the Glasgow and Scottish populations.<p></p> Results: Death rates were higher in people with SMI across all socioeconomic quintiles compared to the Glasgow and Scottish populations, and persisted when suicide was excluded. Differences were largest in the most deprived quintile (794.6 per 10,000 population vs. 274.7 and 252.4 for Glasgow and Scotland respectively). Cause of death varied by socioeconomic status. For those living in the most deprived quintile, higher drug-related deaths occurred in those with SMI compared to local Glasgow and wider Scottish population rates (12.3% vs. 5.9%, p = <0.001 and 5.1% p = 0.002 respectively). A lower proportion of deaths due to cancer in those with SMI living in the most deprived quintile were also observed, relative to the local Glasgow and wider Scottish populations (12.3% vs. 25.1% p = 0.013 and 26.3% p = <0.001). The proportion of suicides was significantly higher in those with SMI living in the more affluent quintiles relative to Glasgow and Scotland (54.6% vs. 5.8%, p = <0.001 and 5.5%, p = <0.001). Discussion and conclusions: Excess mortality in those with SMI occurred across all socioeconomic quintiles compared to the Glasgow and Scottish populations but was most marked in the most deprived quintiles when suicide was excluded as a cause of death. Further work assessing the impact of socioeconomic status on specific causes of premature mortality in SMI is needed

Fifteen new risk loci for coronary artery disease highlight arterial-wall-specific mechanisms

Coronary artery disease (CAD) is a leading cause of morbidity and mortality worldwide. Although 58 genomic regions have been associated with CAD thus far, most of the heritability is unexplained, indicating that additional susceptibility loci await identification. An efficient discovery strategy may be larger-scale evaluation of promising associations suggested by genome-wide association studies (GWAS). Hence, we genotyped 56,309 participants using a targeted gene array derived from earlier GWAS results and performed meta-analysis of results with 194,427 participants previously genotyped, totaling 88,192 CAD cases and 162,544 controls. We identified 25 new SNP-CAD associations (P < 5 × 10(-8), in fixed-effects meta-analysis) from 15 genomic regions, including SNPs in or near genes involved in cellular adhesion, leukocyte migration and atherosclerosis (PECAM1, rs1867624), coagulation and inflammation (PROCR, rs867186 (p.Ser219Gly)) and vascular smooth muscle cell differentiation (LMOD1, rs2820315). Correlation of these regions with cell-type-specific gene expression and plasma protein levels sheds light on potential disease mechanisms

Characterization of Botulinum Neurotoxin Type A Neutralizing Monoclonal Antibodies and Influence of Their Half-Lives on Therapeutic Activity

Botulinum toxins, i.e. BoNT/A to/G, include the most toxic substances known. Since botulism is a potentially fatal neuroparalytic disease with possible use as a biowarfare weapon (Centers for Disease Control and Prevention category A bioterrorism agent), intensive efforts are being made to develop vaccines or neutralizing antibodies. The use of active fragments from non-human immunoglobulins (F(ab')2, Fab', scFv), chemically modified or not, may avoid side effects, but also largely modify the in vivo half-life and effectiveness of these reagents. We evaluated the neutralizing activity of several monoclonal anti-BoNT/A antibodies (mAbs). F(ab')2 fragments, native or treated with polyethyleneglycol (PEG), were prepared from selected mAbs to determine their half-life and neutralizing activity as compared with the initial mAbs. We compared the protective efficiency of the different biochemical forms of anti-toxin mAbs providing the same neutralizing activity. Among fourteen tested mAbs, twelve exhibited neutralizing activity. Fragments from two of the best mAbs (TA12 and TA17), recognizing different epitopes, were produced. These two mAbs neutralized the A1 subtype of the toxin more efficiently than the A2 or A3 subtypes. Since mAb TA12 and its fragments both exhibited the greatest neutralizing activity, they were further evaluated in the therapeutic experiments. These showed that, in a mouse model, a 2- to 4-h interval between toxin and antitoxin injection allows the treatment to remain effective, but also suggested an absence of correlation between the half-life of the antitoxins and the length of time before treatment after botulinum toxin A contamination. These experiments demonstrate that PEG treatment has a strong impact on the half-life of the fragments, without affecting the effectiveness of neutralization, which was maintained after preparation of the fragments. These reagents may be useful for rapid treatment after botulinum toxin A contamination

The significance of the Van Nuys prognostic index in the management of ductal carcinoma in situ

<p>Abstract</p> <p>Background</p> <p>Debate regarding the benefit of radiotherapy after local excision of ductal carcinoma <it>in situ </it>(DCIS) continues. The Van Nuys Prognostic Index (VNPI) is thought to be a useful aid in deciding which patients are at increased risk of local recurrence and who may benefit from adjuvant radiotherapy (RT). Recently published interim data from the Sloane project has showed that the VNPI score did significantly affect the chances of getting planned radiotherapy in the UK, suggesting that British clinicians may already be using this scoring system to assist in decision making. This paper independently assesses the prognostic validity of the VNPI in a British population.</p> <p>Patients and methods</p> <p>A retrospective review was conducted of all patients (n = 215) who underwent breast conserving surgery for DCIS at a single institution between 1997 – 2006. No patients included in the study received additional radiotherapy or hormonal treatment. Kaplan Meier survival curves were calculated, to determine disease free survival, for the total sample and a series of univariate analyses were performed to examine the value of various prognostic factors including the VNPI. The log-rank test was used to determine statistical significance of differential survival rates. Multivariate Cox regression analysis was performed to analyze the significance of the individual components of the VNPI. All analyses were conducted using SPSS software, version 14.5.</p> <p>Results</p> <p>The mean follow-up period was 53 months (range 12–97, SD19.9). Ninety five tumours were high grade (44%) and 84 tumours exhibited comedo necrosis (39%). The closest mean initial excision margin was 2.4 mm (range 0–22 mm, standard deviation 2.8) and a total of 72 tumours (33%) underwent further re-excision. The observed and the actuarial 8 year disease-free survival rates in this study were 91% and 83% respectively. The VNPI score and the presence of comedo necrosis were the only statistically significant prognostic indicators (P < 0.05).</p> <p>Conclusion</p> <p>This follow-up study of 215 patients with DCIS treated with local excision and observation alone is one of the largest series in which rates of recurrence are unaffected by radiation therapy, hormone manipulation or chemotherapy. It has afforded us the opportunity to assess the prognostic impact of patient and tumour characteristics free of any potentially confounding treatment related influences. The results suggest that the VNPI can be used to identify a subset of patients who are at risk of local recurrence and who may potentially benefit from RT.</p

The use of phylogeny to interpret cross-cultural patterns in plant use and guide medicinal plant discovery: an example from Pterocarpus (Leguminosae)

The study of traditional knowledge of medicinal plants has led to discoveries that have helped combat diseases and improve healthcare. However, the development of quantitative measures that can assist our quest for new medicinal plants has not greatly advanced in recent years. Phylogenetic tools have entered many scientific fields in the last two decades to provide explanatory power, but have been overlooked in ethnomedicinal studies. Several studies show that medicinal properties are not randomly distributed in plant phylogenies, suggesting that phylogeny shapes ethnobotanical use. Nevertheless, empirical studies that explicitly combine ethnobotanical and phylogenetic information are scarce.In this study, we borrowed tools from community ecology phylogenetics to quantify significance of phylogenetic signal in medicinal properties in plants and identify nodes on phylogenies with high bioscreening potential. To do this, we produced an ethnomedicinal review from extensive literature research and a multi-locus phylogenetic hypothesis for the pantropical genus Pterocarpus (Leguminosae: Papilionoideae). We demonstrate that species used to treat a certain conditions, such as malaria, are significantly phylogenetically clumped and we highlight nodes in the phylogeny that are significantly overabundant in species used to treat certain conditions. These cross-cultural patterns in ethnomedicinal usage in Pterocarpus are interpreted in the light of phylogenetic relationships.This study provides techniques that enable the application of phylogenies in bioscreening, but also sheds light on the processes that shape cross-cultural ethnomedicinal patterns. This community phylogenetic approach demonstrates that similar ethnobotanical uses can arise in parallel in different areas where related plants are available. With a vast amount of ethnomedicinal and phylogenetic information available, we predict that this field, after further refinement of the techniques, will expand into similar research areas, such as pest management or the search for bioactive plant-based compounds

Identification of multiple integrin β1 homologs in zebrafish (Danio rerio)

BACKGROUND: Integrins comprise a large family of α,β heterodimeric, transmembrane cell adhesion receptors that mediate diverse essential biological functions. Higher vertebrates possess a single β1 gene, and the β1 subunit associates with a large number of α subunits to form the major class of extracellular matrix (ECM) receptors. Despite the fact that the zebrafish (Danio rerio) is a rapidly emerging model organism of choice for developmental biology and for models of human disease, little is currently known about β1 integrin sequences and functions in this organism. RESULTS: Using RT-PCR, complete coding sequences of zebrafish β1 paralogs were obtained from zebrafish embryos or adult tissues. The results show that zebrafish possess two β1 paralogs (β1–1 and β1–2) that have a high degree of identity to other vertebrate β1 subunits. In addition, a third, more divergent, β1 paralog is present (β1–3), which may have altered ligand-binding properties. Zebrafish also have other divergent β1-like transcripts, which are C-terminally truncated forms lacking the transmembrane and cytoplasmic domains. Together with β1–3 these truncated forms comprise a novel group of β1 paralogs, all of which have a mutation in the ADMIDAS cation-binding site. Phylogenetic and genomic analyses indicate that the duplication that gave rise to β1–1 and β1–2 occurred after the divergence of the tetrapod and fish lineages, while a subsequent duplication of the ancestor of β1–2 may have given rise to β1–3 and an ancestral truncated paralog. A very recent tandem duplication of the truncated β1 paralogs appears to have taken place. The different zebrafish β1 paralogs have varied patterns of temporal expression during development. β1–1 and β1–2 are ubiquitously expressed in adult tissues, whereas the other β1 paralogs generally show more restricted patterns of expression. CONCLUSION: Zebrafish have a large set of integrin β1 paralogs. β1–1 and β1–2 may share the roles of the solitary β1 subunit found in other vertebrates, whereas β1–3 and the truncated β1 paralogs may have acquired novel functions

Reconstructing grassland fire history using sedimentary charcoal: Considering count, size and shape

Citation: Leys, B. A., Commerford, J. L., & McLauchlan, K. K. (2017). Reconstructing grassland fire history using sedimentary charcoal: Considering count, size and shape. Plos One, 12(4), 15. doi:10.1371/journal.pone.0176445Fire is a key Earth system process, with 80% of annual fire activity taking place in grassland areas. However, past fire regimes in grassland systems have been difficult to quantify due to challenges in interpreting the charcoal signal in depositional environments. To improve reconstructions of grassland fire regimes, it is essential to assess two key traits: (1) charcoal count, and (2) charcoal shape. In this study, we quantified the number of charcoal pieces in 51 sediment samples of ponds in the Great Plains and tested its relevance as a proxy for the fire regime by examining 13 potential factors influencing charcoal count, including various fire regime components (e.g. the fire frequency, the area burned, and the fire season), vegetation cover and pollen assemblages, and climate variables. We also quantified the width to length (W: L) ratio of charcoal particles, to assess its utility as a proxy of fuel types in grassland environments by direct comparison with vegetation cover and pollen assemblages. Our first conclusion is that charcoal particles produced by grassland fires are smaller than those produced by forest fires. Thus, a mesh size of 120 mu m as used in forested environments is too large for grassland ecosystems. We recommend counting all charcoal particles over 60 mu m in grasslands and mixed grass-forest environments to increase the number of samples with useful data. Second, a W: L ratio of 0.5 or smaller appears to be an indicator for fuel types, when vegetation surrounding the site is before composed of at least 40% grassland vegetation. Third, the area burned within 1060m of the depositional environments explained both the count and the area of charcoal particles. Therefore, changes in charcoal count or charcoal area through time indicate a change in area burned. The fire regimes of grassland systems, including both human and climatic influences on fire behavior, can be characterized by long-term charcoal records

Parent-of-origin-specific allelic associations among 106 genomic loci for age at menarche.

Age at menarche is a marker of timing of puberty in females. It varies widely between individuals, is a heritable trait and is associated with risks for obesity, type 2 diabetes, cardiovascular disease, breast cancer and all-cause mortality. Studies of rare human disorders of puberty and animal models point to a complex hypothalamic-pituitary-hormonal regulation, but the mechanisms that determine pubertal timing and underlie its links to disease risk remain unclear. Here, using genome-wide and custom-genotyping arrays in up to 182,416 women of European descent from 57 studies, we found robust evidence (P < 5 × 10(-8)) for 123 signals at 106 genomic loci associated with age at menarche. Many loci were associated with other pubertal traits in both sexes, and there was substantial overlap with genes implicated in body mass index and various diseases, including rare disorders of puberty. Menarche signals were enriched in imprinted regions, with three loci (DLK1-WDR25, MKRN3-MAGEL2 and KCNK9) demonstrating parent-of-origin-specific associations concordant with known parental expression patterns. Pathway analyses implicated nuclear hormone receptors, particularly retinoic acid and γ-aminobutyric acid-B2 receptor signalling, among novel mechanisms that regulate pubertal timing in humans. Our findings suggest a genetic architecture involving at least hundreds of common variants in the coordinated timing of the pubertal transition