Symptomatic Cavernous Malformation Presenting with Seizure without Hemorrhage: Analysis of Factors Influencing Clinical Presentation

BACKGROUND: Supratentorial cavernous malformations (CMs) can be epileptogenic lesions. However, little is known about clinical comorbidities, medication use, and radiologic features that predict a first seizure presentation without associated CM hemorrhage.METHODS: We queried a prospective registry of consecutive patients with CM established in January 2015. Data regarding clinical presentation, comorbid conditions, daily medication use, and radiologic CM characteristics were collected. Univariate and multivariate regression analysis was performed assessing variables for presentation with seizure without hemorrhage with P values, odds ratios, and 95% confidence intervals reported.RESULTS: Of 202 patients, 58.4% were women, and the average age at diagnosis was 43.7 +/- 16.5 years. Of the patients, 59.4% were symptomatic. In 40.6%, the CM was an incidental finding. Of the 30 patients who presented with a first-time seizure without concomitant hemorrhage, the mean age at diagnosis was 38.4 +/- 14.6 years, and 56.7% were women. Compared with incidental CM, patients with seizure without hemorrhage were younger, had a cortically based, supratentorial lesion, and were less likely to have chronic inflammatory disease or to use aspirin, vitamin D, or statin. Compared with other supratentorial lesions, patients with seizure without hemorrhage more commonly had a temporal lobe CM.CONCLUSIONS: These prospective data provide possible clues to radiologic factors, clinical comorbidities, and medication influences on seizure presentation in patients with CM. Further multicenter studies would be helpful to determine if disease-modifying agents in addition to epileptic medications or surgery might be helpful

Understanding the disorder of the DNA base cytosine on the Au(111) surface

Using ultrahigh vacuum scanning tunneling microscopy (STM) and ab initio density functional theory, we have investigated in detail structures formed by cytosine on the Au(111) surface in clean ultrahigh vacuum conditions. In spite of the fact that the ground state of this DNA base on the surface is shown to be an ordered arrangement of cytosine one-dimensional branches (filaments), this structure has never been observed in our STM experiments. Instead, disordered structures are observed, which can be explained by only a few elementary structural motifs: filaments, five- and sixfold rings, which randomly interconnect with each other forming bent chains, T junctions, and nanocages. The latter may have trapped smaller structures inside. The formation of such an unusual assembly is explained by simple kinetic arguments as a liquid-glass transition. © 2008 American Institute of Physics

Malaria in Sri Lanka: one year post-tsunami

One year ago, the authors of this article reported in this journal on the malaria situation in Sri Lanka prior to the tsunami that hit on 26 December 2004, and estimated the likelihood of a post-tsunami malaria outbreak to be low. Malaria incidence has decreased in 2005 as compared to 2004 in most districts, including the ones that were hit hardest by the tsunami. The malaria incidence (aggregated for the whole country) in 2005 followed the downward trend that started in 2000. However, surveillance was somewhat affected by the tsunami in some coastal areas and the actual incidence in these areas may have been higher than recorded, although there were no indications of this and it is unlikely to have affected the overall trend significantly. The focus of national and international post tsunami malaria control efforts was supply of antimalarials, distribution of impregnated mosquito nets and increased monitoring in the affected area. Internationally donated antimalarials were either redundant or did not comply with national drug policy, however, few seem to have entered circulation outside government control. Despite distribution of mosquito nets, still a large population is relatively exposed to mosquito bites due to inadequate housing. There were no indications of increased malaria vector abundance. Overall it is concluded that the tsunami has not negatively influenced the malaria situation in Sri Lanka

Determinants of the Proinflammatory Action of Ambient Particulate Matter in Immortalized Murine Macrophages

Background: Proximity to traffic-related pollution has been associated with poor respiratory health in adults and children. Objectives: We wished to test the hypothesis that particulate matter (PM) from high-traffic sites would display an enhanced capacity to elicit inflammation. Methods: We examined the inflammatory potential of coarse [2.5–10 μm in aerodynamic diameter (PM2.5–10)] and fine [0.1–2.5 μm in aerodynamic diameter (PM0.1–2.5)] PM collected from nine sites throughout Europe with contrasting traffic contributions. We incubated murine monocytic-macrophagic RAW264.7 cells with PM samples from these sites (20 or 60 μg/cm2) and quantified their capacity to stimulate the release of arachidonic acid (AA) or the production of interleukin-6 and tumor necrosis factor-α (TNFα) as measures of their inflammatory potential. Responses were then related to PM composition: metals, hydrocarbons, anions/cations, and endotoxin content. Results: Inflammatory responses to ambient PM varied markedly on an equal mass basis, with PM2.5–10 displaying the largest signals and contrasts among sites. Notably, we found no evidence of enhanced inflammatory potential at high-traffic sites and observed some of the largest responses at sites distant from traffic. Correlation analyses indicated that much of the sample-to-sample contrast in the proinflammatory response was related to the content of endotoxin and transition metals (especially iron and copper) in PM2.5–10. Use of the metal chelator diethylene triamine pentaacetic acid inhibited AA release, whereas recombinant endotoxin-neutralizing protein partially inhibited TNFα production, demonstrating that different PM components triggered inflammatory responses through separate pathways. Conclusions: We found no evidence that PM collected from sites in close proximity to traffic sources displayed enhanced proinflammatory activity in RAW264.7 cells. Key words: copper, endotoxin, inflammation, iron, macrophages, metals, particulate matter, polyaromatic hydrocarbons. Environ Health Perspect 118:1728–1734 (2010). doi:10.1289/ehp.1002105 [Online 27 July 2010

Prognostic communication in cancer : a critical interpretive synthesis of the literature.

Purpose - For patients with cancer, providing appropriate information about prognosis or chances of recurrent disease remains a difficult area of practice. Much research has suggested that patients want to be given all available information, although the realities of attempting to do this are complex and may be perceived by some as uncaring. A review of recent literature was undertaken to explore the process of disclosure, patient experience and preferences for information regarding prognosis or risk of recurrence. Methods - A systematic approach was taken to searching electronic databases for relevant literature from 2004 to June 2014. Primary research from a range of methodological approaches was included and critical interpretive synthesis was employed to explore themes and identify gaps in the evidence. Results - Twenty papers were identified as appropriate. They were diverse in objectives and patient groups. Themes identified included: the nature of prognostic information, patient need for prognostic information, patient need to maintain hope, balancing hope and realism, patient factors, disease factors and clinician factors. A thematic framework was developed. Conclusions - Patients often struggle to fully understand complex prognostic information. They value help in making sense of this information and generally want information that supports hope. Working with patients to understand and manage the uncertainty of their situation may be particularly valuable. Further research is needed to fully understand the process of prognostic information giving and what information patients want regarding recurrence risk. Research should be aimed at identifying strategies helpful to patients in managing uncertainty inherent in their situation.</p

Cochrane Qualitative and Implementation Methods Group Guidance Series - paper 1: Introduction

Cochrane Reviews are systematic reviews of primary research in human health care and health policy, and are internationally recognized health c are resources for use in a decision-making process. 1 Cochrane works collaboratively with contributors around the world to produce authoritative, relevant, and reliable reviews. Coch rane reviews are commonly used in a guideline development process to determine recommendations fo r practice. The Cochrane Qualitative and Implementation Methods Group provide methodolog ical advice and guidance to Cochrane as well as leading methodological developm ent to benefit the wider qualitative evidence synthesis community. In this introductory paper 1 we briefly outline the evolution of qualitative and mixed-method synthesis methods, the role of qualitative and mixed- method syntheses in a decision-making process, and the contribution of qualitative and mixed-method syntheses to understanding complexity in complex intervention reviews. We then introduce a series of papers that provide Coch rane guidance on conducting qualitative and mixed-method evidence syntheses for a decision- making context

Words cluster phonetically beyond phonotactic regularities

Recent evidence suggests that cognitive pressures associated with language acquisition and use could affect the organization of the lexicon. On one hand, consistent with noisy channel models of language (e.g., Levy, 2008), the phonological distance between wordforms should be maximized to avoid perceptual confusability (a pressure for dispersion). On the other hand, a lexicon with high phonological regularity would be simpler to learn, remember and produce (e.g., Monaghan et al., 2011) (a pressure for clumpiness). Here we investigate wordform similarity in the lexicon, using measures of word distance (e.g., phonological neighborhood density) to ask whether there is evidence for dispersion or clumpiness of wordforms in the lexicon. We develop a novel method to compare lexicons to phonotactically-controlled baselines that provide a null hypothesis for how clumpy or sparse wordforms would be as the result of only phonotactics. Results for four languages, Dutch, English, German and French, show that the space of monomorphemic wordforms is clumpier than what would be expected by the best chance model according to a wide variety of measures: minimal pairs, average Levenshtein distance and several network properties. This suggests a fundamental drive for regularity in the lexicon that conflicts with the pressure for words to be as phonologically distinct as possible. Keywords: Linguistics; Lexical design; Communication; Phonotactic

Fingerprinting microbiomes towards screening for microbial antibiotic resistance

There is an increasing need to investigate microbiomes in their entirety in a variety of contexts ranging from environmental to human health scenarios. This requirement is becoming increasingly important with emergence of antibiotic resistance. In general, more conventional approaches are too expensive and/or time-consuming and often predicated on prior knowledge of the microorganisms one wishes to study. Herein, we propose the use of biospectroscopy tools as relatively high-throughput, non-destructive approaches to profile microbiomes under study. Fourier-transform infrared (FTIR) or Raman spectroscopy both generate fingerprint spectra of biological material and such spectra can readily be subsequently classed according to biochemical changes in the microbiota, such as emergence of antibiotic resistance. FTIR spectroscopy techniques generally can only be applied to desiccated material whereas Raman approaches can be applied to more hydrated samples. The ability to readily fingerprint microbiomes could lend itself to new approaches in determining microbial behaviours and emergence of antibiotic resistance

Portrait of Candida albicans Adherence Regulators

Cell-substrate adherence is a fundamental property of microorganisms that enables them to exist in biofilms. Our study focuses on adherence of the fungal pathogen Candida albicans to one substrate, silicone, that is relevant to device-associated infection. We conducted a mutant screen with a quantitative flow-cell assay to identify thirty transcription factors that are required for adherence. We then combined nanoString gene expression profiling with functional analysis to elucidate relationships among these transcription factors, with two major goals: to extend our understanding of transcription factors previously known to govern adherence or biofilm formation, and to gain insight into the many transcription factors we identified that were relatively uncharacterized, particularly in the context of adherence or cell surface biogenesis. With regard to the first goal, we have discovered a role for biofilm regulator Bcr1 in adherence, and found that biofilm regulator Ace2 is a major functional target of chromatin remodeling factor Snf5. In addition, Bcr1 and Ace2 share several target genes, pointing to a new connection between them. With regard to the second goal, our findings reveal existence of a large regulatory network that connects eleven adherence regulators, the zinc-response regulator Zap1, and approximately one quarter of the predicted cell surface protein genes in this organism. This limited yet sensitive glimpse of mutant gene expression changes had thus defined one of the broadest cell surface regulatory networks in C. albicans