RNA editing signature during myeloid leukemia cell differentiation

Adenosine deaminases acting on RNA (ADARs) are key proteins for hematopoietic stem cell self-renewal and for survival of differentiating progenitor cells. However, their specific role in myeloid cell maturation has been poorly investigated. Here we show that ADAR1 is present at basal level in the primary myeloid leukemia cells obtained from patients at diagnosis as well as in myeloid U-937 and THP1 cell lines and its expression correlates with the editing levels. Upon phorbol-myristate acetate or Vitamin D3/granulocyte macrophage colony-stimulating factor (GM-CSF)-driven differentiation, both ADAR1 and ADAR2 enzymes are upregulated, with a concomitant global increase of A-to-I RNA editing. ADAR1 silencing caused an editing decrease at specific ADAR1 target genes, without, however, interfering with cell differentiation or with ADAR2 activity. Remarkably, ADAR2 is absent in the undifferentiated cell stage, due to its elimination through the ubiquitin–proteasome pathway, being strongly upregulated at the end of the differentiation process. Of note, peripheral blood monocytes display editing events at the selected targets similar to those found in differentiated cell lines. Taken together, the data indicate that ADAR enzymes play important and distinct roles in myeloid cells

Prolonged hemophagocytic lymphohistiocytosis syndrome as an initial presentation of Hodgkin lymphoma: a case report

<p>Abstract</p> <p>Introduction</p> <p>Hemophagocytic lymphohistiocytosis is an immune-mediated syndrome that typically has a rapidly progressive course that can result in pancytopenia, coagulopathy, multi-system organ failure and death.</p> <p>Case presentation</p> <p>A 57-year-old Caucasian woman was referred in fulminant hemophagocytic lymphohistiocytosis, with fever, pancytopenia, splenomegaly, mental status changes and respiratory failure. She was found to have stage IV classical Hodgkin lymphoma, in addition to Epstein-Barr virus and cytomegalovirus viremia. Her presentation was preceded by a 3-year prodrome consisting of cytopenia and fever that were partially controlled by steroids and azathioprine.</p> <p>Conclusion</p> <p>Fulminant hemophagocytic lymphohistiocytosis may follow a prodromal phase that possesses features suggestive of a chronic form of hemophagocytic lymphohistiocytosis, but which may also resemble immune cytopenias of other causes. A diagnosis of hemophagocytic lymphohistiocytosis should be considered in the setting of chronic pancytopenia.</p

Empirical Analysis of Factors Affecting Confirmation Bias Levels of Software Engineers

Confirmation bias is defined as the tendency of people to seek evidence that verifies a hypothesis rather than seeking evidence to falsify it. Due to the confirmation bias, defects may be introduced in a software product during requirements analysis, design, implementation and/or testing phases. For instance, testers may exhibit confirmatory behavior in the form of a tendency to make the code run rather than employing a strategic approach to make it fail. As a result, most of the defects that have been introduced in the earlier phases of software development may be overlooked leading to an increase in software defect density. In this paper, we quantify confirmation bias levels in terms of a single derived metric. However, the main focus of this paper is the analysis of factors affecting confirmation bias levels of software engineers. Identification of these factors can guide project managers to circumvent negative effects of confirmation bias, as well as providing guidance for the recruitment and effective allocation of software engineers. In this empirical study, we observed low confirmation bias levels among participants with logical reasoning and hypothesis testing skills

"Don't wait for them to come to you, you go to them". A qualitative study of recruitment approaches in community based walking programmes in the UK

<p>Abstract</p> <p>Background</p> <p>This study aimed to examine the experiences of walking promotion professionals on the range and effectiveness of recruitment strategies used within community based walking programmes within the United Kingdom.</p> <p>Methods</p> <p>Two researchers recruited and conducted semi-structured interviews with managers and project co-ordinators of community based walking programmes, across the UK, using a purposive sampling frame. Twenty eight interviews were conducted, with community projects targeting participants by age, physical activity status, socio-demographic characteristics (i.e. ethnic group) or by health status. Three case studies were also conducted with programmes aiming to recruit priority groups and also demonstrating innovative recruitment methods. Data analysis adopted an approach using analytic induction.</p> <p>Results</p> <p>Two types of programmes were identified: those with explicit health aims and those without. Programme aims which required targeting of specific groups adopted more specific recruitment methods. The selection of recruitment method was dependent on the respondent’s awareness of ‘what works’ and the resource capacity at their disposal. Word of mouth was perceived to be the most effective means of recruitment but using this approach took time and effort to build relationships with target groups, usually through a third party. Perceived effectiveness of recruitment was assessed by number of participants rather than numbers of the right participants. Some programmes, particularly those targeting younger adult participants, recruited using new social communication media. Where adopted, social marketing recruitment strategies tended to promote the ‘social’ rather than the ‘health’ benefits of walking.</p> <p>Conclusions</p> <p>Effective walking programme recruitment seems to require trained, strategic, labour intensive, word-of-mouth communication, often in partnerships, in order to understand needs and develop trust and motivation within disengaged sedentary communities. Walking promotion professionals require better training and resources to deliver appropriate recruitment strategies to reach priority groups.</p

Informed consent in veterinary medicine: ethical implications for the profession and the animal 'patient'

Informed consent processes are a vital component of both human and veterinary medicine. Current practice encourages veterinarians to learn from insights in the human medical field about how best to achieve valid consent. However, drawing on published literature in veterinary and medical ethics, this paper identifies considerable differences between the purposes of veterinary and human medical consent. Crucially, it is argued that the legal status of animal patients as ‘property’ has implications for the ethical role of veterinary informed consent and the protection of the animal ‘patient’. It is suggested that veterinary informed consent should be viewed as an ethical pivot point where the multiple responsibilities of a veterinary professional converge. In practice, balancing these responsibilities creates considerable ethical challenges. As an example, the paper discusses the renewed call for UK veterinarians to make animal welfare their first priority; we predict that this imperative may increasingly cause veterinary informed consent to become an ethical pressure point due to tensions caused by the often conflicting interests of animals, owners and the veterinary profession. In conclusion, the paper argues that whilst gaining informed consent can often be presented as a robust ethical justification in human medicine, the same cannot be said in veterinary medicine. If the veterinary profession wish to prioritise animal welfare, there is an urgent need to re-evaluate the nature of authority gained through owner informed consent and to consider whether animal patients might need to be better protected outside the consent process in certain circumstances

Seasonal variation of water uptake of a Quercus suber tree in Central Portugal

Hydraulic redistribution (HR) is the phenomenon where plant roots transfer water between soil horizons of different water potential. When dry soil is a stronger sink for water loss from the plant than transpiration, water absorbed by roots in wetter soil horizons is transferred toward, and exuded into dry soil via flow reversals through the roots. Reverse flow is a good marker of HR and can serve as a useful tool to study it over the long-term. Seasonal variation of water uptake of a Quercus suber tree was studied from late winter through autumn 2003 at Rio Frio near Lisbon, Portugal. Sap flow was measured in five small shallow roots (diameter of 3–4 cm), 1 to 2 m from the tree trunk and in four azimuths and at different xylem depths at the trunk base, using the heat field deformation method (HFD). The pattern of sap flow differed among lateral roots as soil dried with constant positive flow in three roots and reverse flow in two other roots during the night when transpiration ceased. Rain modified the pattern of flow in these two roots by eliminating reverse flow and substantially increasing water uptake for transpiration during the day. The increase in water uptake in three other roots following rain was not so substantial. In addition, the flux in individual roots was correlated to different degrees with the flux at different radial depths and azimuthal directions in trunk xylem. The flow in outer trunk xylem seemed to be mostly consistent with water movement from surface soil horizons, whereas deep roots seemed to supply water to the whole cross-section of sapwood. When water flow substantially decreased in shallow lateral roots and the outer stem xylem during drought, water flow in the inner sapwood was maintained, presumably due to its direct connection to deep roots. Results also suggest the importance of the sap flow sensor placement, in relation to sinker roots, as to whether lateral roots might be found to exhibit reverse flow during drought. This study is consistent with the dimorphic rooting habit of Quercus suber trees in which deep roots access groundwater to supply superficial roots and the whole tree, when shallow soil layers were dry

Patient Discomfort Associated with the Use of Intra-arterial Iodinated Contrast Media: A Meta-Analysis of Comparative Randomized Controlled Trials

<p>Abstract</p> <p>Background</p> <p>Discomfort characterized by pain and warmth are common adverse effects associated with the use of intra-arterial iodinated contrast media (CM). The objective of this review was to pool patient-reported outcomes available from head-to-head randomized controlled trials (RCTs) and to compare the discomfort rates associated with iso-osmolar contrast media (IOCM; i.e., iodixanol) to those reported with various low-osmolar contrast media (LOCM).</p> <p>Methods</p> <p>A review of the literature published between 1990 and 2009 available through Medline, Medline Preprints, Embase, Biological Abstracts, BioBase, Cab Abstracts, International Pharmaceutical Abstracts, Life Sciences Collection, Inside Conferences, Energy Database, Engineering Index and Technology Collection was performed to compare rates of discomfort associated with the use of the IOCM (iodixanol) vs. various LOCM agents in head-to-head RCTs. All trials with a Jadad score ≥2 that reported patient discomfort data following intra-arterial administration of CM were reviewed, coded, and extracted.</p> <p>Results</p> <p>A total of 22 RCTs (n = 8087) were included. Overall discomfort (regardless of severity) was significantly different between patients receiving IOCM and various LOCMs (risk difference [RD] -0.049; 95% confidence interval [CI]: -0.076, -0.021; p = 0.001). IOCM was favored over all LOCMs combined with a summary RD value of -0.188 (95% CI: -0.265, -0.112; p < 0.001) for incidence of pain, regardless of severity. A greater reduction in the magnitude of pain was observed with IOCM (iodixanol), particularly with selective limb and carotid/intracerebral procedures. Similarly, the meta-analysis of warmth sensation, regardless of severity, favored IOCM over LOCMs with an RD of -0.043 (95% CI: -0.074, -0.011; p = 0.008). A positive linear relationship was observed between the discomfort effect size and age and a negative relationship with increasing proportion of women. The opposite trends were observed with warmth sensation.</p> <p>Conclusions</p> <p>IOCM was associated with less frequent and severe patient discomfort during intra-arterial administration. These data support differences in osmolality as a possible determinant of CM discomfort.</p

Mis-Spliced Transcripts of Nicotinic Acetylcholine Receptor α6 Are Associated with Field Evolved Spinosad Resistance in Plutella xylostella (L.)

The evolution of insecticide resistance is a global constraint to agricultural production. Spinosad is a new, low-environmental-risk insecticide that primarily targets nicotinic acetylcholine receptors (nAChR) and is effective against a wide range of pest species. However, after only a few years of application, field evolved resistance emerged in the diamondback moth, Plutella xylostella, an important pest of brassica crops worldwide. Spinosad resistance in a Hawaiian population results from a single incompletely recessive and autosomal gene, and here we use AFLP linkage mapping to identify the chromosome controlling resistance in a backcross family. Recombinational mapping with more than 700 backcross progeny positioned a putative spinosad target, nAChR alpha 6 (Pxα6), at the resistance locus, PxSpinR. A mutation within the ninth intron splice junction of Pxα6 results in mis-splicing of transcripts, which produce a predicted protein truncated between the third and fourth transmembrane domains. Additional resistance-associated Pxα6 transcripts that excluded the mutation containing exon were detected, and these were also predicted to produce truncated proteins. Identification of the locus of resistance in this important crop pest will facilitate field monitoring of the spread of resistance and offer insights into the genetic basis of spinosad resistance in other species

Jet energy measurement with the ATLAS detector in proton-proton collisions at root s=7 TeV

The jet energy scale and its systematic uncertainty are determined for jets measured with the ATLAS detector at the LHC in proton-proton collision data at a centre-of-mass energy of √s = 7TeV corresponding to an integrated luminosity of 38 pb-1. Jets are reconstructed with the anti-kt algorithm with distance parameters R=0. 4 or R=0. 6. Jet energy and angle corrections are determined from Monte Carlo simulations to calibrate jets with transverse momenta pT≥20 GeV and pseudorapidities {pipe}η{pipe}<4. 5. The jet energy systematic uncertainty is estimated using the single isolated hadron response measured in situ and in test-beams, exploiting the transverse momentum balance between central and forward jets in events with dijet topologies and studying systematic variations in Monte Carlo simulations. The jet energy uncertainty is less than 2. 5 % in the central calorimeter region ({pipe}η{pipe}<0. 8) for jets with 60≤pT<800 GeV, and is maximally 14 % for pT<30 GeV in the most forward region 3. 2≤{pipe}η{pipe}<4. 5. The jet energy is validated for jet transverse momenta up to 1 TeV to the level of a few percent using several in situ techniques by comparing a well-known reference such as the recoiling photon pT, the sum of the transverse momenta of tracks associated to the jet, or a system of low-pT jets recoiling against a high-pT jet. More sophisticated jet calibration schemes are presented based on calorimeter cell energy density weighting or hadronic properties of jets, aiming for an improved jet energy resolution and a reduced flavour dependence of the jet response. The systematic uncertainty of the jet energy determined from a combination of in situ techniques is consistent with the one derived from single hadron response measurements over a wide kinematic range. The nominal corrections and uncertainties are derived for isolated jets in an inclusive sample of high-pT jets. Special cases such as event topologies with close-by jets, or selections of samples with an enhanced content of jets originating from light quarks, heavy quarks or gluons are also discussed and the corresponding uncertainties are determined. © 2013 CERN for the benefit of the ATLAS collaboration