Trends in thyroid hormone prescribing and consumption in the UK

<p>Abstract</p> <p>Background</p> <p>Thyroid hormone replacement is one of the most commonly prescribed and cost effective treatments for a chronic disease. There have been recent changes in community prescribing policies in many areas of the UK that have changed patient access to necessary medications. This study aimed to provide a picture of thyroid hormone usage in the UK and to survey patient opinion about current community prescribing policies for levothyroxine.</p> <p>Methods</p> <p>Data on community prescriptions for thyroid hormones in England between 1998 and 2007, provided by the Department of Health, were collated and analysed. A survey of UK members of a patient support organisation (the British Thyroid Foundation) who were taking levothyroxine was carried out.</p> <p>Results</p> <p>The amount of prescribed thyroid hormones used in England has more than doubled, from 7 to almost 19 million prescriptions, over the last 10 years. The duration of prescriptions has reduced from 60 to 45 days, on average over the same time. Two thousand five hundred and fifty one responses to the patient survey were received. Thirty eight percent of levothyroxine users reported receiving prescriptions of 28 days' duration. 59% of respondents reported being dissatisfied with 28-day prescribing.</p> <p>Conclusion</p> <p>Amongst users of levothyroxine, there is widespread patient dissatisfaction with 28-day prescription duration. Analysis of the full costs of 28-day dispensing balanced against the potential savings of reduced wastage of thyroid medications, suggests that this is unlikely to be an economically effective public health policy.</p

Nanopods: A New Bacterial Structure and Mechanism for Deployment of Outer Membrane Vesicles

Background: Bacterial outer membrane vesicles (OMV) are packets of periplasmic material that, via the proteins and other molecules they contain, project metabolic function into the environment. While OMV production is widespread in proteobacteria, they have been extensively studied only in pathogens, which inhabit fully hydrated environments. However, many (arguably most) bacterial habitats, such as soil, are only partially hydrated. In the latter, water is characteristically distributed as films on soil particles that are, on average thinner, than are typical OMV (ca. ≤10 nm water film vs. 20 to >200 nm OMV;). Methodology/Principal Findings: We have identified a new bacterial surface structure, termed a "nanopod", that is a conduit for projecting OMV significant distances (e.g., ≥6 µm) from the cell. Electron cryotomography was used to determine nanopod three-dimensional structure, which revealed chains of vesicles within an undulating, tubular element. By using immunoelectron microscopy, proteomics, heterologous expression and mutagenesis, the tubes were determined to be an assembly of a surface layer protein (NpdA), and the interior structures identified as OMV. Specific metabolic function(s) for nanopods produced by Delftia sp. Cs1-4 are not yet known. However, a connection with phenanthrene degradation is a possibility since nanopod formation was induced by growth on phenanthrene. Orthologs of NpdA were identified in three other genera of the Comamonadaceae family, and all were experimentally verified to form nanopods. Conclusions/Significance: Nanopods are new bacterial organelles, and establish a new paradigm in the mechanisms by which bacteria effect long-distance interactions with their environment. Specifically, they create a pathway through which cells can effectively deploy OMV, and the biological activity these transmit, in a diffusion-independent manner. Nanopods would thus allow environmental bacteria to expand their metabolic sphere of influence in a manner previously unknown for these organisms

Associations between maternal participation in agricultural decision-making and child nutrition in semiarid Kenya

This study explores the associations between childhood growth measures and maternal participation in agricultural decision-making in chronically food-insecure semiarid Kenya. We collected anthropometric measures from 221 mother and child pairs. Maternal participation in agricultural decision-making was measured in a follow-up study. Using Kruskal–Wallis H test and Dunn’s pairwise comparison, we find a statistically significant positive association between child growth and maternal participation in agricultural decision-making. Similar associations are found when controlled for social–demographic variables, particularly among poor households, male-headed households, daughters, children 6–16 months old, and mothers with normal body mass index. The research contributes to our understanding in the nexus of agriculture, gender dynamics, and childhood undernutrition in rural African contexts

Synthesis of global satellite observations of magmatic and volcanic deformation: implications for volcano monitoring & the lateral extent of magmatic domains

Global Synthetic Aperture Radar (SAR) measurements made over the past decades provide insights into the lateral extent of magmatic domains, and capture volcanic process on scales useful for volcano monitoring. Satellite-based SAR imagery has great potential for monitoring topographic change, the distribution of eruptive products and surface displacements (InSAR) at subaerial volcanoes. However, there are challenges in applying it routinely, as would be required for the reliable operational assessment of hazard. The deformation detectable depends upon satellite repeat time and swath widths, relative to the spatial and temporal scales of volcanological processes. We describe the characteristics of InSAR-measured volcano deformation over the past two decades, highlighting both the technique’s capabilities and its limitations as a monitoring tool. To achieve this, we draw on two global datasets of volcano deformation: the Smithsonian Institution Volcanoes of the World database and the Centre for the Observation and Modelling of Earthquakes, Volcanoes and Tectonics volcano deformation catalogue, as well as compiling some measurement characteristics and interpretations from the primary literature. We find that a higher proportion of InSAR observations capture non-eruptive and non-magmatic processes than those from ground-based instrument networks, and that both transient ( 5 years) deformation episodes are under-represented. However, satellite radar is already used to assess the development of extended periods of unrest and long-lasting eruptions, and improved spatial resolution and coverage have resulted in the detection of previously unrecognised deformation at both ends of the spatial scale (~ 10 to > 1000 km²). ‘Baseline’ records of past InSAR measurements, including ‘null’ results, are fundamental for any future interpretation of interferograms in terms of hazard‚ both by providing information about past deformation at an individual volcano, and for assessing the characteristics of deformation that are likely to be detectable (and undetectable) using InSAR. More than half of all InSAR deformation signals attributed to magmatic processes have sources in the shallow crust (< 5 km depth). While the depth distribution of InSAR-derived deformation sources is affected by measurement limitations, their lateral distribution provides information about the extent of active magmatic domains. Deformation is common (24% of all potentially magmatic events) at loci ≥5 km away from the nearest active volcanic vent. This demonstrates that laterally extensive active magmatic domains are not exceptional, but can comprise the shallowest part of trans-crustal magmatic systems in a range of volcanic settings

Criminal and Noncriminal Psychopathy: The Devil is in the Detail

Brooks, NS ORCiD: 0000-0003-1784-099XPsychopathy is prevalent and problematic in criminal populations, but is also found to be present in noncriminal populations. In 1992, Robert Hare declared that psychopaths may also “be found in the boardroom”, which has since been followed by an interest in the issue of noncriminal, or even successful, psychopathy. In this chapter, the paradox of criminal and noncriminal psychopathy is discussed with specific attention given to the similarities and differences that account for psychopathic personality across contexts. That psychopathy is a condition typified by a constellation of traits and behaviours requires wider research across diverse populations, and thus the streams of research related to criminal and noncriminal psychopathy are presented and the implications of these contrasting streams are explored

Correlations of Behavioral Deficits with Brain Pathology Assessed through Longitudinal MRI and Histopathology in the R6/2 Mouse Model of HD

Huntington's disease (HD) is caused by the expansion of a CAG repeat in the huntingtin (HTT) gene. The R6/2 mouse model of HD expresses a mutant version of exon 1 HTT and develops motor and cognitive impairments, a widespread huntingtin (HTT) aggregate pathology and brain atrophy. Despite the vast number of studies that have been performed on this model, the association between the molecular and cellular neuropathology with brain atrophy, and with the development of behavioral phenotypes remains poorly understood. In an attempt to link these factors, we have performed longitudinal assessments of behavior (rotarod, open field, passive avoidance) and of regional brain abnormalities determined through magnetic resonance imaging (MRI) (whole brain, striatum, cortex, hippocampus, corpus callosum), as well as an end-stage histological assessment. Detailed correlative analyses of these three measures were then performed. We found a gender-dependent emergence of motor impairments that was associated with an age-related loss of regional brain volumes. MRI measurements further indicated that there was no striatal atrophy, but rather a lack of striatal growth beyond 8 weeks of age. T2 relaxivity further indicated tissue-level changes within brain regions. Despite these dramatic motor and neuroanatomical abnormalities, R6/2 mice did not exhibit neuronal loss in the striatum or motor cortex, although there was a significant increase in neuronal density due to tissue atrophy. The deposition of the mutant HTT (mHTT) protein, the hallmark of HD molecular pathology, was widely distributed throughout the brain. End-stage histopathological assessments were not found to be as robustly correlated with the longitudinal measures of brain atrophy or motor impairments. In conclusion, modeling pre-manifest and early progression of the disease in more slowly progressing animal models will be key to establishing which changes are causally related. © 2013 Rattray et al

The control of attentional target selection in a colour/colour conjunction task

To investigate the time course of attentional object selection processes in visual search tasks where targets are defined by a combination of features from the same dimension, we measured the N2pc component as an electrophysiological marker of attentional object selection during colour/colour conjunction search. In Experiment 1, participants searched for targets defined by a combination of two colours, while ignoring distractor objects that matched only one of these colours. Reliable N2pc components were triggered by targets and also by partially matching distractors, even when these distractors were accompanied by a target in the same display. The target N2pc was initially equal in size to the sum of the two N2pc components to the two different types of partially matching distractors, and became superadditive from about 250 ms after search display onset. Experiment 2 demonstrated that the superadditivity of the target N2pc was not due to a selective disengagement of attention from task-irrelevant partially matching distractors. These results indicate that attention was initially deployed separately and in parallel to all target-matching colours, before attentional allocation processes became sensitive to the presence of both matching colours within the same object. They suggest that attention can be controlled simultaneously and independently by multiple features from the same dimension, and that feature-guided attentional selection processes operate in parallel for different target-matching objects in the visual field

Discerning Tumor Status from Unstructured MRI Reports—Completeness of Information in Existing Reports and Utility of Automated Natural Language Processing

Information in electronic medical records is often in an unstructured free-text format. This format presents challenges for expedient data retrieval and may fail to convey important findings. Natural language processing (NLP) is an emerging technique for rapid and efficient clinical data retrieval. While proven in disease detection, the utility of NLP in discerning disease progression from free-text reports is untested. We aimed to (1) assess whether unstructured radiology reports contained sufficient information for tumor status classification; (2) develop an NLP-based data extraction tool to determine tumor status from unstructured reports; and (3) compare NLP and human tumor status classification outcomes. Consecutive follow-up brain tumor magnetic resonance imaging reports (2000–­2007) from a tertiary center were manually annotated using consensus guidelines on tumor status. Reports were randomized to NLP training (70%) or testing (30%) groups. The NLP tool utilized a support vector machines model with statistical and rule-based outcomes. Most reports had sufficient information for tumor status classification, although 0.8% did not describe status despite reference to prior examinations. Tumor size was unreported in 68.7% of documents, while 50.3% lacked data on change magnitude when there was detectable progression or regression. Using retrospective human classification as the gold standard, NLP achieved 80.6% sensitivity and 91.6% specificity for tumor status determination (mean positive predictive value, 82.4%; negative predictive value, 92.0%). In conclusion, most reports contained sufficient information for tumor status determination, though variable features were used to describe status. NLP demonstrated good accuracy for tumor status classification and may have novel application for automated disease status classification from electronic databases

Using an in-vitro biofilm model to assess the virulence potential of Bacterial Vaginosis or non-Bacterial Vaginosis Gardnerella vaginalis isolates

Gardnerella vaginalis is the most common species found in bacterial vaginosis (BV). However, it is also present in a significant proportion of healthy women and G. vaginalis vaginal colonization does not always lead to BV. In an effort to better understand the differences between G. vaginalis isolated from women with a positive (BV) versus a negative (non-BV) diagnosis of BV, we compared the virulence potential of 7 BV and 7 non-BV G. vaginalis isolates and assessed the virulence factors related to biofilm formation, namely: initial adhesion and cytotoxic effect, biofilm accumulation, susceptibility to antibiotics, and transcript levels of the known vaginolysin, and sialidase genes. Furthermore, we also determined the ability of G. vaginalis to displace lactobacilli previously adhered to HeLa cells. Our results showed that non-BV strains were less virulent than BV strains, as suggested by the lower cytotoxicity and initial adhesion to Hela cells. Significant differences in expression of known virulence genes were also detected, further suggesting a higher virulence potential of the BV associated G. vaginalis. Importantly, we demonstrated that BV associated G. vaginalis were able to displace pre-coated vaginal protective lactobacilli and we hypothesize this to be a trigger for BV development.European Union funds (FEDER/COMPETE) and by national funds (FCT) under the project with reference FCOMP-01-0124-FEDER-008991 (PTDC/BIA-MIC/098228/2008). FCT Strategic Project of UID/BIO/04469/2013 unit the project NORTE-07-0124-FEDER-000027, co-funded by the Programa Operacional Regional do Norte(ON.2 – O Novo Norte), QREN, FEDER, and the project RECI/BBB-EBI/0179/2012 (FCOMP-01-0124-FEDER-027462). FCT individual fellowship SFRH/BD/93963/2013

CCL5 regulation of mucosal chlamydial immunity and infection

<p>Abstract</p> <p>Background</p> <p>Following genital chlamydial infection, an early T helper type 1 (Th1)-associated immune response precedes the activation and recruitment of specific Th1 cells bearing distinct chemokine receptors, subsequently leading to the clearance of <it>Chlamydia</it>. We have shown that CCR5, a receptor for CCL5, is crucial for protective chlamydial immunity. Our laboratory and others have also demonstrated that CCL5 deficiencies found in man and animals can increase the susceptibility and progression of infectious diseases by modulating mucosal immunity. These findings suggest the CCR5-CCL5 axis is necessary for optimal chlamydial immunity. We hypothesized CCL5 is required for protective humoral and cellular immunity against <it>Chlamydia</it>.</p> <p>Results</p> <p>The present study revealed that CCR5 and CCL5 mRNAs are elevated in the spleen, iliac lymph nodes (ILNs), and genital mucosa following <it>Chlamydia muriduram </it>challenge. Antibody (Ab)-mediated inhibition of CCL5 during genital chlamydial infection suppressed humoral and Th1 > Th2 cellular responses by splenic-, ILN-, and genital mucosa-derived lymphocytes. Antigen (Ag)-specific proliferative responses of CD4⁺T cells from spleen, ILNs, and genital organs also declined after CCL5 inhibition.</p> <p>Conclusion</p> <p>The suppression of these responses correlated with delayed clearance of <it>C. muriduram</it>, which indicate chlamydial immunity is mediated by Th1 immune responses driven in part by CCL5. Taken together with other studies, the data show that CCL5 mediates the temporal recruitment and activation of leukocytes to mitigate chlamydial infection through enhancing adaptive mucosal humoral and cellular immunity.</p