Deletions of the derivative chromosome 9 occur at the time of the Philadelphia translocation and provide a powerful and independent prognostic indicator in chronic myeloid leukemia

Chronic myeloid leukemia (CML) is characterized by formation of the BCR-ABL fusion gene, usually as a consequence of the Philadelphia (Ph) translocation between chromosomes 9 and 22. Large deletions on the derivative chromosome 9 have recently been reported, but it was unclear whether deletions arose during disease progression or at the time of the Ph translocation. Fluorescence in situ hybridization (FISH) analysis was used to assess the deletion status of 253 patients with CML. The strength of deletion status as a prognostic indicator was then compared to the Sokal and Hasford scoring systems. The frequency of deletions was similar at diagnosis and after disease progression but was significantly increased in patients with variant Ph translocations. In patients with a deletion, all Ph+ metaphases carried the deletion. The median survival of patients with and without deletions was 38 months and 88 months, respectively (P = .0001). By contrast the survival difference between Sokal or Hasford high-risk and non-high-risk patients was of only borderline significance (P = .057 and P = .034). The results indicate that deletions occur at the time of the Ph translocation. An apparently simple reciprocal translocation may therefore result in considerable genetic heterogeneity ab initio, a concept that is likely to apply to other malignancies associated with translocations. Deletion status is also a powerful and independent prognostic factor for patients with CML. The prognostic significance of deletion status should now be studied prospectively and, if confirmed, should be incorporated into management decisions and the analysis of clinical trials. (C) 2001 by The American Society of Hematology

Searching for Earth analogues around the nearest stars: the disk age-metallicity relation and the age distribution in the Solar Neighbourhood

The chemical composition of Earth's atmosphere has undergone substantial evolution over the course of its history. It is possible, even likely, that terrestrial planets in other planetary systems have undergone similar changes; consequently, the age distribution of nearby stars is an important consideration in designing surveys for Earth-analogues. Valenti & Fischer (2005) provide age and metallicity estimates for 1039 FGK dwarfs in the Solar Neighbourhood. Using the Hipparcos catalogue as a reference to calibrate potential biases, we have extracted volume-limited samples of nearby stars from the Valenti-Fischer dataset. Unlike other recent investigations, our analysis shows clear evidence for an age-metallicity relation in the local disk, albeit with substantial dispersion at any epoch. The mean metallicity increases from -0.3 dex at a lookback time of ~10 Gyrs to +0.15 dex at the present day. Supplementing the Valenti-Fischer measurements with literature data to give a complete volume-limited sample, the age distribution of nearby FGK dwarfs is broadly consistent with a uniform star-formation rate over the history of the Galactic disk. In striking contrast, most stars known to have planetary companions are younger than 5 Gyrs; however, stars with planetary companions within 0.4 AU have a significantly flatter age distribution, indicating that those systems are stable on timescales of many Gyrs. Several of the older, lower metallicity host stars have enhanced [alpha/Fe] ratios, implying membership of the thick disk. If the frequency of terrestrial planets is also correlated with stellar metallicity, then the median age of such planetary system is likely to be ~3 Gyrs. We discuss the implications of this hypothesis in designing searches for Earth analogues among the nearby stars.Comment: Accepted for publication in Ap

Variation in the Diagnosis and Management of Appendicitis at Canadian Pediatric Hospitals

Objectives The objective was to characterize the variations in practice in the diagnosis and management of children admitted to hospitals from Canadian pediatric emergency departments (EDs) with suspected appendicitis, specifically the timing of surgical intervention, ED investigations, and management strategies. Methods Twelve sites participated in this retrospective health record review. Children aged 3 to 17 years admitted to the hospital with suspected appendicitis were eligible. Site-specific demographics, investigations, and interventions performed were recorded and compared. Factors associated with after-hours surgery were determined using generalized estimating equations logistic regression. Results Of the 619 children meeting eligibility criteria, surgical intervention was performed in 547 (88%). After-hours surgery occurred in 76 of the 547 children, with significant variation across sites (13.9%, 95% confidence interval = 7.1% to 21.6%, p \u3c 0.001). The overall perforation rate was 17.4% (95 of 547), and the negative appendectomy rate was 6.8% (37 of 547), varying across sites (p = 0.004 and p = 0.036, respectively). Use of inflammatory markers (p \u3c 0.001), blood cultures (p \u3c 0.001), ultrasound (p = 0.001), and computed tomography (p = 0.001) also varied by site. ED administration of narcotic analgesia and antibiotics varied across sites (p \u3c 0.001 and p = 0.001, respectively), as did the type of surgical approach (p \u3c 0.001). After-hours triage had a significant inverse association with after-hours surgery (p = 0.014). Conclusions Across Canadian pediatric EDs, there exists significant variation in the diagnosis and management of children with suspected appendicitis. These results indicate that the best diagnostic and management strategies remain unclear and support the need for future prospective, multicenter studies to identify strategies associated with optimal patient outcomes

<i>Trypanosoma evansi</i>: Genetic variability detected using amplified restriction fragment length polymorphism (AFLP) and random amplified polymorphic DNA (RAPD) analysis of Kenyan isolates

We compared two methods to generate polymorphic markers to investigate the population genetics of Trypanosoma evansi; random amplified polymorphic DNA (RAPD) and amplified restriction fragment length polymorphism (AFLP) analyses. AFLP accessed many more polymorphisms than RAPD. Cluster analysis of the AFLP data showed that 12 T.evansi isolates were very similar (‘type A’) whereas 2 isolates differed substantially (‘type B’). Type A isolates have been generally regarded as genetically identical but AFLP analysis was able to identify multiple differences between them and split the type A T. evansi isolates into two distinct clades

Water vapor in the starburst galaxy NGC 253: A new nuclear maser?

22 GHz water vapor emission was observed toward the central region of the spiral starburst galaxy NGC 253. Monitoring observations with the 100-m telescope at Effelsberg and measurements with the BnC array of the VLA reveal three distinct velocity components, all of them blueshifted with respect to the systemic velocity. The main component arises from a region close to the dynamical center and is displaced by <1 arcsec from the putative nuclear continuum source. The bulk of this maser component is spread over an area not larger than 70 x 50 mas. Its radial velocity may be explained by masing gas that is part of a nuclear accretion disk or of a counterrotating kinematical subsystem or by gas that is entrained by the nuclear superwind or by an expanding supernova shell. A weaker feature, located 5 arcsec to the northeast, is likely related to an optically obscured site of massive star formation.Comment: 6 pages, 4 Postscript figures, A&A Main Journa

What is the 'problem' that outreach work seeks to address and how might it be tackled? Seeking theory in a primary health prevention programme

&lt;b&gt;Background&lt;/b&gt; Preventive approaches to health are disproportionately accessed by the more affluent and recent health improvement policy advocates the use of targeted preventive primary care to reduce risk factors in poorer individuals and communities. Outreach has become part of the health service response. Outreach has a long history of engaging those who do not otherwise access services. It has, however, been described as eclectic in its purpose, clientele and mode of practice; its effectiveness is unproven. Using a primary prevention programme in the UK as a case, this paper addresses two research questions: what are the perceived problems of non-engagement that outreach aims to address; and, what specific mechanisms of outreach are hypothesised to tackle these.&lt;p&gt;&lt;/p&gt; &lt;b&gt;Methods&lt;/b&gt; Drawing on a wider programme evaluation, the study undertook qualitative interviews with strategically selected health-care professionals. The analysis was thematically guided by the concept of 'candidacy' which theorises the dynamic process through which services and individuals negotiate appropriate service use.&lt;p&gt;&lt;/p&gt; &lt;b&gt;Results&lt;/b&gt; The study identified seven types of engagement 'problem' and corresponding solutions. These 'problems' lie on a continuum of complexity in terms of the challenges they present to primary care. Reasons for non-engagement are congruent with the concept of 'candidacy' but point to ways in which it can be expanded.&lt;p&gt;&lt;/p&gt; &lt;b&gt;Conclusions&lt;/b&gt; The paper draws conclusions about the role of outreach in contributing to the implementation of inequalities focused primary prevention and identifies further research needed in the theoretical development of both outreach as an approach and candidacy as a conceptual framework

Radiation-dominated area metric cosmology

We provide further crucial support for a refined, area metric structure of spacetime. Based on the solution of conceptual issues, such as the consistent coupling of fermions and the covariant identification of radiation fields on area metric backgrounds, we show that the radiation-dominated epoch of area metric cosmology is equivalent to that epoch in standard Einstein cosmology. This ensures, in particular, successful nucleosynthesis. This surprising result complements the previously derived prediction of a small late-time acceleration of an area metric universe.Comment: 23 pages, no figures; references adde

A Conceptual Basis for Feature Engineering

The gulf between the user and the developer perspectives lead to diculties in producing successful software systems. Users are focused on the problem domain, where the system&apos;s features are the primary concern. Developers are focused on the solution domain, where the system&apos;s life-cycle artifacts are key. Presently, there is little understanding of how to narrow this gulf

Light Curves and Period Changes of Type II Cepheids in the Globular Clusters M3 and M5

Light curves in the B, V, and I_c passbands have been obtained for the type II Cepheids V154 in M3 and V42 and V84 in M5. Alternating cycle behavior, similar to that seen among RV Tauri variables, is confirmed for V84. Old and new observations, spanning more than a century, show that V154 has increased in period while V42 has decreased in period. V84, on the other hand, has shown large, erratic changes in period that do not appear to reflect the long term evolution of V84 through the HR diagram.Comment: 28 pages, 12 figure

Radiation damage in the LHCb vertex locator

The LHCb Vertex Locator (VELO) is a silicon strip detector designed to reconstruct charged particle trajectories and vertices produced at the LHCb interaction region. During the first two years of data collection, the 84 VELO sensors have been exposed to a range of fluences up to a maximum value of approximately 45 × 1012 1 MeV neutron equivalent (1 MeV neq). At the operational sensor temperature of approximately −7 °C, the average rate of sensor current increase is 18 μA per fb−1, in excellent agreement with predictions. The silicon effective bandgap has been determined using current versus temperature scan data after irradiation, with an average value of Eg = 1.16±0.03±0.04 eV obtained. The first observation of n+-on-n sensor type inversion at the LHC has been made, occurring at a fluence of around 15 × 1012 of 1 MeV neq. The only n+-on-p sensors in use at the LHC have also been studied. With an initial fluence of approximately 3 × 1012 1 MeV neq, a decrease in the Effective Depletion Voltage (EDV) of around 25 V is observed. Following this initial decrease, the EDV increases at a comparable rate to the type inverted n+-on-n type sensors, with rates of (1.43±0.16) × 10−12 V/ 1 MeV neq and (1.35±0.25) × 10−12 V/ 1 MeV neq measured for n+-on-p and n+-on-n type sensors, respectively. A reduction in the charge collection efficiency due to an unexpected effect involving the second metal layer readout lines is observed