A comparison between direct and pan-derived measurements of the isotopic composition of atmospheric waters

The stable isotopes of water can be used to examine and quantify the contribution to atmospheric moisture from evaporation, transpiration and surface-waters. However, obtaining extensive and ongoing time series data of the isotopic composition of atmospheric moisture has been difficult. Presented here is an alternate method using an isotope mass balance approach to estimate the isotopic composition of atmospheric moisture using water samples collected from class A evaporation pans. While this evaporation pan method does not provide the high-resolution time series data that can be obtained from an isotope analyser taking in-situ measurements of atmospheric moisture, the method is relatively simple and inexpensive to set-up and maintain. In this preliminary investigation, a comparison between the isotopic composition of atmospheric moisture estimated from the evaporation pan method and in-situ measurements of the isotopic composition of water vapour using a Fourier Transform Infrared (FTIR) spectrometer deployed at the Lucas Heights weather station in New South Wales is undertaken. Through comparison of the two series of hydrogen isotope data, an assessment of the evaporation pan method can be made. Although there was some agreement between the isotopic composition of vapour measured by the FTIR spectrometer and the estimation for the atmospheric moisture (R2 = 0.49), the comparison is sensitive to climatic parameters that vary significantly within a 24-hour period such as the relative humidity of air and the air and pan temperatures. Inverting the model to use the FTIR spectrometer measurements at an hourly resolution improved the performance of the model (R2 =0.57). However, this also revealed that the model produced more depleted values of the evaporation pan water isotopes than those observed. In contrast, there was a variable relationship between the modelled and observed isotope values of atmospheric moisture. These conflicting results will need to be resolved before the evaporation pan method is broadly applied in isotope hydrology. © 2011 The Modelling and Simulation Society of Australia and New Zealand Inc

Quality of life and mental health of patients with vascular malformations in a single specialist center in the United Kingdom

OBJECTIVE: Patients with vascular malformations suffer from chronic debilitating symptoms that have been shown to contribute negatively to their quality of life (QoL) and mental health. Despite this, the current literature evaluating the QoL and mental health of patients with vascular malformations remains scarce. Our aim was to evaluate the QoL and mental health of patients with vascular malformations. METHODS: We prospectively analyzed the validated health-related QoL (HRQoL) questionnaires: the RAND Health Care 36-Item Short Form Survey (SF-36), Hospital Anxiety and Depression Scale (HADS), and visual analogue score for pain reported by 253 patients with vascular malformations in a specialist center of vascular anomalies in the UK over two years. RESULTS: Patients with vascular malformations reported significantly poorer SF-36 scores in all domains compared with the UK general population. Patients with low-flow vascular malformations and arteriovenous malformations reported little variations in SF-36, HADS, and visual analogue score for pain scores. No significant association was found between age and any of the health-related QoL scores, other than the physical functioning in SF-36. Female patients reported significantly lower physical and social functioning of SF-36 and worse HADS-Depression than their male counterparts. Patients with syndromic vascular malformations reported significantly lower SF-36 scores in role-physical, role-emotional and bodily pain than nonsyndromic vascular malformations. CONCLUSIONS: This study concluded that patients with vascular malformations reported worse QoL than the UK general population. Therefore, the assessment and management of QoL and mental health should be incorporated into the overall treatment strategies of patients with vascular malformations

A Relational Event Approach to Modeling Behavioral Dynamics

This chapter provides an introduction to the analysis of relational event data (i.e., actions, interactions, or other events involving multiple actors that occur over time) within the R/statnet platform. We begin by reviewing the basics of relational event modeling, with an emphasis on models with piecewise constant hazards. We then discuss estimation for dyadic and more general relational event models using the relevent package, with an emphasis on hands-on applications of the methods and interpretation of results. Statnet is a collection of packages for the R statistical computing system that supports the representation, manipulation, visualization, modeling, simulation, and analysis of relational data. Statnet packages are contributed by a team of volunteer developers, and are made freely available under the GNU Public License. These packages are written for the R statistical computing environment, and can be used with any computing platform that supports R (including Windows, Linux, and Mac).

A Geographically-Restricted but Prevalent Mycobacterium tuberculosis Strain Identified in the West Midlands Region of the UK between 1995 and 2008

Background: We describe the identification of, and risk factors for, the single most prevalent Mycobacterium tuberculosis strain in the West Midlands region of the UK.Methodology/Principal Findings: Prospective 15-locus MIRU-VNTR genotyping of all M. tuberculosis isolates in the West Midlands between 2004 and 2008 was undertaken. Two retrospective epidemiological investigations were also undertaken using univariable and multivariable logistic regression analysis. The first study of all TB patients in the West Midlands between 2004 and 2008 identified a single prevalent strain in each of the study years (total 155/3,056 (5%) isolates). This prevalent MIRU-VNTR profile (32333 2432515314 434443183) remained clustered after typing with an additional 9-loci MIRU-VNTR and spoligotyping. The majority of these patients (122/155, 79%) resided in three major cities located within a 40 km radius. From the apparent geographical restriction, we have named this the "Mercian" strain. A multivariate analysis of all TB patients in the West Midlands identified that infection with a Mercian strain was significantly associated with being UK-born (OR = 9.03, 95% CI = 4.56-17.87, p 65 years old (OR = 0.25, 95% CI = 0.09-0.67, p < 0.01). A second more detailed investigation analyzed a cohort of 82 patients resident in Wolverhampton between 2003 and 2006. A significant association with being born in the UK remained after a multivariate analysis (OR = 9.68, 95% CI = 2.00-46.78, p < 0.01) and excess alcohol intake and cannabis use (OR = 6.26, 95% CI = 1.45-27.02, p = .01) were observed as social risk factors for infection.Conclusions/Significance: The continued consistent presence of the Mercian strain suggests ongoing community transmission. Whilst significant associations have been found, there may be other common risk factors yet to be identified. Future investigations should focus on targeting the relevant risk groups and elucidating the biological factors that mediate continued transmission of this strain

Proliferative and anti-proliferative effects of dietary levels of phytoestrogens in rat pituitary GH3/B6/F10 cells - the involvement of rapidly activated kinases and caspases

<p>Abstract</p> <p>Background</p> <p>Phytoestogens are a group of lipophillic plant compounds that can have estrogenic effects in animals; both tumorigenic and anti-tumorigenic effects have been reported. Prolactin-secreting adenomas are the most prevalent form of pituitary tumors in humans and have been linked to estrogen exposures. We examined the proliferative effects of phytoestrogens on a rat pituitary tumor cell line, GH₃/B₆/F₁₀, originally subcloned from GH₃cells based on its ability to express high levels of the membrane estrogen receptor-α.</p> <p>Methods</p> <p>We measured the proliferative effects of these phytoestrogens using crystal violet staining, the activation of several mitogen-activated protein kinases (MAPKs) and their downstream targets via a quantitative plate immunoassay, and caspase enzymatic activities.</p> <p>Results</p> <p>Four phytoestrogens (coumestrol, daidzein, genistein, and <it>trans</it>-resveratrol) were studied over wide concentration ranges. Except <it>trans</it>-resveratrol, all phytoestrogens increased GH₃/B₆/F₁₀cell proliferation at some concentration relevant to dietary levels. All four phytoestrogens attenuated the proliferative effects of estradiol when administered simultaneously. All phytoestrogens elicited MAPK and downstream target activations, but with time course patterns that often differed from that of estradiol and each other. Using selective antagonists, we determined that MAPKs play a role in the ability of these phytoestrogens to elicit these responses. In addition, except for <it>trans</it>-resveratrol, a serum removal-induced extrinsic apoptotic pathway was blocked by these phytoestrogens.</p> <p>Conclusion</p> <p>Phytoestrogens can block physiological estrogen-induced tumor cell growth <it>in vitro </it>and can also stimulate growth at high dietary concentrations in the absence of endogenous estrogens; these actions are correlated with slightly different signaling response patterns. Consumption of these compounds should be considered in strategies to control endocrine tumor cell growth, such as in the pituitary.</p

The GATA1s isoform is normally down-regulated during terminal haematopoietic differentiation and over-expression leads to failure to repress MYB, CCND2 and SKI during erythroid differentiation of K562 cells

Background: Although GATA1 is one of the most extensively studied haematopoietic transcription factors little is currently known about the physiological functions of its naturally occurring isoforms GATA1s and GATA1FL in humans—particularly whether the isoforms have distinct roles in different lineages and whether they have non-redundant roles in haematopoietic differentiation. As well as being of general interest to understanding of haematopoiesis, GATA1 isoform biology is important for children with Down syndrome associated acute megakaryoblastic leukaemia (DS-AMKL) where GATA1FL mutations are an essential driver for disease pathogenesis. &lt;p/&gt;Methods: Human primary cells and cell lines were analyzed using GATA1 isoform specific PCR. K562 cells expressing GATA1s or GATA1FL transgenes were used to model the effects of the two isoforms on in vitro haematopoietic differentiation. &lt;p/&gt;Results: We found no evidence for lineage specific use of GATA1 isoforms; however GATA1s transcripts, but not GATA1FL transcripts, are down-regulated during in vitro induction of terminal megakaryocytic and erythroid differentiation in the cell line K562. In addition, transgenic K562-GATA1s and K562-GATA1FL cells have distinct gene expression profiles both in steady state and during terminal erythroid differentiation, with GATA1s expression characterised by lack of repression of MYB, CCND2 and SKI. &lt;p/&gt;Conclusions: These findings support the theory that the GATA1s isoform plays a role in the maintenance of proliferative multipotent megakaryocyte-erythroid precursor cells and must be down-regulated prior to terminal differentiation. In addition our data suggest that SKI may be a potential therapeutic target for the treatment of children with DS-AMKL

The genome sequence of <i>Trypanosoma brucei gambiense</i>, causative agent of chronic Human African Trypanosomiasis

&lt;p&gt;&lt;b&gt;Background:&lt;/b&gt; &lt;i&gt;Trypanosoma brucei gambiense&lt;/i&gt; is the causative agent of chronic Human African Trypanosomiasis or sleeping sickness, a disease endemic across often poor and rural areas of Western and Central Africa. We have previously published the genome sequence of a &lt;i&gt;T. b. brucei&lt;/i&gt; isolate, and have now employed a comparative genomics approach to understand the scale of genomic variation between &lt;i&gt;T. b. gambiense&lt;/i&gt; and the reference genome. We sought to identify features that were uniquely associated with &lt;i&gt;T. b. gambiense&lt;/i&gt; and its ability to infect humans.&lt;/p&gt; &lt;p&gt;&lt;b&gt;Methods and findings:&lt;/b&gt; An improved high-quality draft genome sequence for the group 1 &lt;i&gt;T. b. gambiense&lt;/i&gt; DAL 972 isolate was produced using a whole-genome shotgun strategy. Comparison with &lt;i&gt;T. b. brucei&lt;/i&gt; showed that sequence identity averages 99.2% in coding regions, and gene order is largely collinear. However, variation associated with segmental duplications and tandem gene arrays suggests some reduction of functional repertoire in &lt;i&gt;T. b. gambiense&lt;/i&gt; DAL 972. A comparison of the variant surface glycoproteins (VSG) in &lt;i&gt;T. b. brucei&lt;/i&gt; with all &lt;i&gt;T. b. gambiense&lt;/i&gt; sequence reads showed that the essential structural repertoire of VSG domains is conserved across &lt;i&gt;T. brucei&lt;/i&gt;.&lt;/p&gt; &lt;p&gt;&lt;b&gt;Conclusions:&lt;/b&gt; This study provides the first estimate of intraspecific genomic variation within &lt;i&gt;T. brucei&lt;/i&gt;, and so has important consequences for future population genomics studies. We have shown that the &lt;i&gt;T. b. gambiense&lt;/i&gt; genome corresponds closely with the reference, which should therefore be an effective scaffold for any &lt;i&gt;T. brucei&lt;/i&gt; genome sequence data. As VSG repertoire is also well conserved, it may be feasible to describe the total diversity of variant antigens. While we describe several as yet uncharacterized gene families with predicted cell surface roles that were expanded in number in &lt;i&gt;T. b. brucei&lt;/i&gt;, no &lt;i&gt;T. b. gambiense&lt;/i&gt;-specific gene was identified outside of the subtelomeres that could explain the ability to infect humans.&lt;/p&gt