Mesenteric desmoid tumor developing on the site of an excised gastrointestinal stromal tumor

We present a case of a rare and unusual occurrence of a desmoid tumor at the site of a resected gastrointestinal stromal tumor and mimicking a recurrence, with a brief discussion of the management of desmoid tumors

Tumour-Associated Tissue Factor (TF)-mRNA Is A Precursor for Rapid TF-Microvesicle Release and A Potential Predictive Marker for the Risk of Pulmonary Embolism (PE) in Gastrointestinal Cancer Patients

Predicting which cancer patients are at risk of thrombosis remains a key challenge to effective thromboprophylaxis. This study was based on the hypothesis that the rapid release of TF-containing MV occurs in cancer cells that possess high levels of TF mRNA, permitting the transient but amplified TF-protein production in response to cellular activation. To gather preliminary clinical evidence for this hypothesis the correlation between the levels of tumour-associated TF mRNA and incidence of Pulmonary Embolism (PE) in Gastrointestinal cancer patients (GI) was assessed using stringently-selected patient cohorts. Furthermore, the rapid TF-MV release was assessed in three cell lines with high TF mRNA in which protein-translation or mRNA-transcription were inhibited separately. On applying the exclusion criteria, the study accrued 9 clinical samples with incidental PE (colonic n=5; gastroesophageal n=4) which were type, gender and stage of cancer matched one-to-one with patients without PE (9+9 samples). Total-RNA was extracted from the samples using a FFPE-RNA extraction kit and TF mRNA was quantified using a quantitative real-time PCR procedure along with a standard curve prepared using in vitro-transcribed TF mRNA. Relative amounts of PAR2 mRNA were also determined. Analysis of absolute amounts of tumour-associated TF mRNA showed significant increase in patients who developed PE (mean=26.931±15.371 pg/100ng-total RNA; median=5.340 pg/100ng-total RNA; range=0.4-131.43 pg/100ng-total RNA) compared to those who didn’t (mean=0.098±0.023 pg/100ng-total RNA; median=0.110 pg/100ng-total RNA; range=0-0.19 pg/100ng-total RNA). Receiver Operating Characteristic (ROC) analysis returned an area under the curve of 1. In contrast, no significant difference in PAR2 mRNA was recorded. To provide an explanation for these findings, inhibition of protein-translation using cycloheximide prevented the incorporation of TF but not the MV release. However, blocking of RNA-transcription did not prevent TF-MV release. In conclusion, this is a first demonstration of a strong correlation between the risk of PE in GI cancer and the levels of tumour-TF mRNA, and further supports the hypothesis that the process is driven by the rapid translation of mRNA into TF-protein, following stimulation

Estimating the microbiological risks associated with inland flood events:bridging theory and models of pathogen transport

Flooding is known to facilitate infectious disease transmission, yet quantitative research on microbiological risks associated with floods has been limited. Pathogen fate and transport models provide a framework to examine interactions between landscape characteristics, hydrology, and waterborne disease risks, but have not been widely developed for flood conditions. We critically examine capabilities of current hydrological models to represent unusual flow paths, non-uniform flow depths, and unsteady flow velocities that accompany flooding. We investigate the theoretical linkages between hydrodynamic processes and spatio-temporally variable suspension and deposition of pathogens from soils and sediments; pathogen dispersion in flow; and concentrations of constituents influencing pathogen transport and persistence. Identifying gaps in knowledge and modeling practice, we propose a research agenda to strengthen microbial fate and transport modeling applied to inland floods: 1) development of models incorporating pathogen discharges from flooded sources (e.g., latrines), effects of transported constituents on pathogen persistence, and supply-limited pathogen transport; 2) studies assessing parameter identifiability and comparing model performance under varying degrees of process representation, in a range of settings; 3) development of remotely sensed datasets to support modeling of vulnerable, data-poor regions; and 4) collaboration between modelers and field-based researchers to expand the collection of useful data in situ

Numerical and Experimental Study on the Addition of Surface Roughness to Micro-Propellers

Micro aerial vehicles are making a large impact in applications such as search-and-rescue, package delivery, and recreation. Unfortunately, these diminutive drones are currently constrained to carrying small payloads, in large part because they use propellers optimized for larger aircraft and inviscid flow regimes. Fully realizing the potential of emerging microflyers requires next-generation propellers that are specifically designed for low-Reynolds number conditions and that include new features advantageous in highly viscous flows. One aspect that has received limited attention in the literature is the addition of roughness to propeller blades as a method of reducing drag and increasing thrust. To investigate this possibility, we used large eddy simulation to conduct a numerical investigation of smooth and rough propellers. Our results indicate that roughness produces a 2% increase in thrust and a 5% decrease in power relative to a baseline smooth propeller operating at the same Reynolds number of Rec = 6500, held constant by rotational speed. We corroborated our numerical findings using thrust-stand-based experiments of 3D-printed propellers identical to those of the numerical simulations. Our study confirms that surface roughness is an additional parameter within the design space for micro-propellers that will lead to unprecedented drone efficiencies and payloads.Comment: 23 Pages, 9 Figure

Analysis of UK and European NOx and VOC emission scenarios in the Defra model intercomparison exercise

This is a PDF file of an unedited manuscript that has been accepted for publication. The manuscript will undergo copyediting, typesetting, and review of the resulting proof before it is published in its final form. Please note that during the production process errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertainSimple emission scenarios have been implemented in eight United Kingdom air quality models with the aim of assessing how these models compared when addressing whether photochemical ozone formation in southern England was NOx- or VOC-sensitive and whether ozone precursor sources in the UK or in the Rest of Europe (RoE) were the most important during July 2006. The suite of models included three Eulerian-grid models (three implementations of one of these models), a Lagrangian atmospheric dispersion model and two moving box air parcel models. The assignments as to NOx- or VOC-sensitive and to UK- versus RoE-dominant, turned out to be highly variable and often contradictory between the individual models. However, when the assignments were filtered by model performance on each day, many of the contradictions could be eliminated. Nevertheless, no one model was found to be the 'best' model on all days, indicating that no single air quality model could currently be relied upon to inform policymakers robustly in terms of NOx- versus VOC-sensitivity and UK- versus RoE-dominance on each day. It is important to maintain a diversity in model approaches.Peer reviewedFinal Accepted Versio

“It doesn’t mean I’m useless” How do young people experiencing psychosis contribute to their families and why are their contributions sometimes overlooked?

Purpose: Psychosis is often seen as a “burden” on families. and affected individuals frequently hold a negative view of themselves. This study explored the ways in which young adults who have experienced first episode psychosis (FEP) make a positive contribution within their families. Methods: Fifteen participants (seven young people with experience of psychosis and eight relatives) were interviewed separately. Their accounts were analysed using grounded theory methodology (Charmaz, 2006). Results: For many individuals, their experience had led to a catastrophic redefinition of their identity. However, they continued to contribute significantly both within their families and within their wider communities. The redefinition of identity sometimes appeared to create a ‘perceptual filter’ whereby both the person themselves and family members overlooked or minimised their contribution, focusing instead on being alert to signs of psychosis or illness. Conclusions: Shame and a focus on symptoms rather than achievements and contributions can significantly limit opportunities, expectations, and movement beyond an illness identity. It is important for clinicians to be aware of this and to help young people and their families to notice and value positive contribution, and so promote recovery, well-being and post-traumatic growth

With a little help from my goals : integrating intergoal facilitation with the theory of planned behaviour to predict physical activity

Reproduced with permission from British Journal of Health Psychology © The British Psychological Society 2010.Peer reviewedPostprin

Rapid measurement of 8-oxo-7,8-dihydro-2 0 -deoxyguanosine in human biological matrices using ultra-high-performance liquid chromatography-tandem mass spectrometry

a b s t r a c t Interaction of reactive oxygen species with DNA results in a variety of modifications, including 8-oxo-7,8-dihydro-2 0 -deoxyguanosine (8-oxodG), which has been extensively studied as a biomarker of oxidative stress. Oxidative stress is implicated in a number of pathophysiological processes relevant to obstetrics and gynecology; however, there is a lack of understanding as to the precise role of oxidative stress in these processes. We aimed to develop a rapid, validated assay for the accurate quantification of 8-oxodG in human urine using solid-phase extraction and ultra-high-performance liquid chromatography-tandem mass spectrometry (UHPLC-MS/MS) and then investigate the levels of 8-oxodG in several fluids of interest to obstetrics and gynecology. Using UHPLC-MS/MS, 8-oxodG eluted after 3.94 min with an RSD for 15 injections of 0.07%. The method was linear between 0.95 and 95 nmol/L with LOD and LOQ of 5 and 25 fmol on-column, respectively. Accuracy and precision were 98.7-101.0 and o10%, respectively, over three concentrations of 8-oxodG. Recovery from urine was 88% with intra-and interday variations of 4.0 and 10.2%, respectively. LOQ from urine was 0.9 pmol/ml. Rank order from the greatest to lowest 8-oxodG concentration was urine 4 seminal plasma 4 amniotic fluid 4plasma4serum 4peritoneal fluid, and it was not detected in saliva. Urine concentrations normalized to creatinine (n ¼ 15) ranged between 0.55 and 1.95 pmol/mmol creatinine. We describe, for the first time, 8-oxodG concentrations in human seminal plasma, peritoneal fluid, amniotic fluid, and breast milk, as well as in urine, plasma, and serum, using a rapid UHPLC-MS/MS method that will further facilitate biomonitoring of oxidative stress

Szisztémás mycosisok és hasonló infekciók központi idegrendszeri manifesztációi = Manifestations of systemic mycoses and related infections in the central nervous system

A hétköznapi klinikai gyakorlatban a központi idegrendszer gombás fertőzései gyakoribbá váltak. Ennek leginkább ismert okai a kortikoszteroidok, immunszuppresszív gyógyszerek, citosztatikumok, antibiotikumok egyre szélesebb körű alkalmazása, az AIDS elterjedése, az életben tartható koraszülöttek mind nagyobb száma. A szerzők a diagnosztikus problémák illusztrálására eseteket mutatnak be. Esetismertetés: 1. Multifokális haemorrhagiás agyi infarktus generalizált aspergillosis következtében, köpenysejtes malignus lymphomában. 2. Éretlen koraszülöttben kialakult cerebralis microabscessusok szisztémás candidiasis talaján. 3. A comb térfoglaló daganatát utánzó, az agyban radiológiailag metasztázisnak tűnő tályogot, a tüdőben gyulladást okozó lethalis actinomycosis. 4. Idegsebészeti szövetmintából diagnosztizált nocardiosis. A visszatérő, migráló pneumonia, majd agyi tályogok miatt hosszasan kezelt beteg a megfelelő terápiára gyógyult. Megbeszélés: Fel kell készülnünk a veszélyeztetett betegek gombás infekciójának kialakulására – elsősorban aspergillosisra és candidiasisra –, ezek jelentős része a központi idegrendszerre is ráterjed. Az actinomycosis és a nocardiosis kezelésre jobban reagál, felismerésük, kezelésük életmentő. Következtetések: Terápiás kilátásaink javulnak, ha a nagy rizikójú betegek jelentős mortalitást okozó mycosisainak lehetőségével számolva, azokat időben – még az idegrendszeri részvétel előtt – kórismézzük és kezeljük. | In the everyday practice the mycotic infections of the CNS have become more and more frequent. The main causes are the wide-ranging use of corticosteroids, immunosuppressive, cytostatic medicaments and antibiotica, the spreading of the AIDS, the increasing number of surviving immature newborns. To illustrate the diagnostic difficulties, authors report some cases. Case reports: 1. Multifocal hemorrhagic infarcts of the brain, caused by generalized aspergillosis in mantle cell malignant lymphoma. 2. Cerebral microabscesses, caused by systemic candidiasis in a premature infant. 3. Lethal case of actinomycosis, mimicking a space occupying tumour in the thigh and with an abscess in the brain, radiologically indicated as a metastasis. The cause of death was actinomycotic pneumonia. 4. A successfully treated and recovered case of a patient with recurrent pneumonia and multiplex brain abscesses, caused by filamentous microorganism of a Nocardia species revealed by the histological examination of the neurosurgical specimen. Discussion and conclusions: We have to be aware for the development of the mycotic and related infections of endangered patients. Aspergillosis and candidiasis play the most significant role in the involvement of CNS. Actinomycosis and nocardiosis are more sensitive for the treatment, so their diagnosis is of life-saving importance. The therapeutic chances of high risk patients with aspergillosis and candidiasis will be definitively better, if the infection is recognized and appropriatly treated before the appearance of the involvement of the CNS

Sequence-Based Association and Selection Scans Identify Drug Resistance Loci in the Plasmodium Falciparum Malaria Parasite

Through rapid genetic adaptation and natural selection, the Plasmodium falciparum parasite—the deadliest of those that cause malaria—is able to develop resistance to antimalarial drugs, thwarting present efforts to control it. Genome-wide association studies (GWAS) provide a critical hypothesis-generating tool for understanding how this occurs. However, in P. falciparum, the limited amount of linkage disequilibrium hinders the power of traditional array-based GWAS. Here, we demonstrate the feasibility and power improvements gained by using whole-genome sequencing for association studies. We analyzed data from 45 Senegalese parasites and identified genetic changes associated with the parasites’ in vitro response to 12 different antimalarials. To further increase statistical power, we adapted a common test for natural selection, XP-EHH (cross-population extended haplotype homozygosity), and used it to identify genomic regions associated with resistance to drugs. Using this sequence-based approach and the combination of association and selection-based tests, we detected several loci associated with drug resistance. These loci included the previously known signals at pfcrt, dhfr, and pfmdr1, as well as many genes not previously implicated in drug-resistance roles, including genes in the ubiquitination pathway. Based on the success of the analysis presented in this study, and on the demonstrated shortcomings of array-based approaches, we argue for a complete transition to sequence-based GWAS for small, low linkage-disequilibrium genomes like that of P. falciparum.Molecular and Cellular BiologyOrganismic and Evolutionary Biolog