Review of clinical, cytogenetic, and molecular aspects of Ph-negative CML

Abstract Between 1985 and 1989, many cases of Philadelphia (Ph) chromosome negative chronic myelogenous leukemia (CML) were reported. For this review, the following selection criteria were used: the original articles on Ph-negative cases should provide clinical, hematologic, cytogenetic as well as molecular data. In addition, eight unpublished cases of Ph-negative CML are included that were studied in our institute during the last two years. Our purpose was to correlate presence or absence of the Ph rearrangement with the clinical features in an attempt to test whether the entity “Ph-negative CML” really exists and to identify the pathologic characteristics, frequency of occurrence, prognosis for survival, and underlying molecular mechanisms. Data on Ph-negative CML patients were compared with data on Ph-positive CML, atypical CML (aCML), and chronic myelomonocytic leukemia (CMMoL), reported in the same papers as the Ph negative patients. Essential for comparison of data from the different investigators appeared to be a clear description of criteria they used to establish the diagnosis CML, or alternatively a complete presentation of data for all patients reported in the articles. In most cases. Ph-negative CML was distinguishable from CMMoL and aCML, using simple criteria, e.g., differential count of peripheral blood and absence of dysplasia in the bone marrow. Cytogenetic analysis showed normal karyotype in most cases of Ph-negative CML. Interestingly, in cases with abnormal karyotype, chromosome 9 band q34 was relatively frequently involved in translocations with other chromosomes than chromosome 22, suggesting a variant Ph translocation not visible by cytogenetic techniques. This assumption was confirmed by molecular analysis, demonstrating bcr-abl rearrangement in 9 out of 10 of the latter cases. Results of cytogenetic and molecular investigations in 136 cases of Ph-negative CML reviewed in this article clearly indicated that molecular techniques are valuable tools for identification of bcr-abl rearrangements, indicative for the Ph translocation. The different mechanisms responsible for bcr-abl rearrangement in Ph-negative CML patients are discussed. The question remains whether all Ph-negative CML patients will have bcr-abl rearrangements, or whether alternative mechanisms will be identified that are responsible for this disease

An Inner Gaseous Disk around the Herbig Be Star MWC 147

We present high-spectral-resolution, optical spectra of the Herbig Be star MWC 147, in which we spectrally resolve several emission lines, including the [O I] lines at 6300 and 6363\deg. Their highly symmetric, double-peaked line profiles indicate that the emission originates in a rotating circumstellar disk. We deconvolve the Doppler-broadened [O I] emission lines to obtain a measure of emission as a function of distance from the central star. The resulting radial surface brightness profiles are in agreement with a disk structure consisting of a flat, inner, gaseous disk and a flared, outer, dust disk. The transition between these components at 2 to 3 AU corresponds to the estimated dust sublimation radius. The width of the double-peaked Mg II line at 4481\deg suggests that the inner disk extends to at least 0.10 AU, close to the corotation radius.Comment: accepted for ApJ Letters (Oct. 2010

In Conversation with Mubin Shaikh: From Salafi Jihadist to Undercover Agent inside the "Toronto 18" Terrorist Group

This interview with former undercover agent Mubin Shaikh can help academics and security practitioners understand the key role played and the challenges faced by covert human intelligence sources within domestic terrorist groups. The interview highlights the identity crisis, the personal factors, and the allure of jihadi militancy that initially drove Shaikh to join a Salafi jihadist group. It investigates Shaikh’s process of disengagement from the Salafi jihadist belief system and his rediscovery of a moderate, inclusive, and benevolent form of Islam. It explores his work as an undercover agent for the Canadian Security Intelligence Service, the Royal Canadian Mounted Police, and the Integrated National Security Enforcement Team responsible for disrupting domestic terrorist groups. The “Toronto 18” terrorist cell, the key role played by undercover agents in preventing terrorist action, and the challenges posed by entrapment are also discussed

Warm and hot circumstellar gas in V1647 Ori during the 2008-2009 outburst

The pre-main sequence star V1647 Ori started a new outburst in August 2008. From October 2008 to February 2009 we monitored V1647 Ori, obtaining quasi-simultaneous VLT-CRIRES near-IR spectroscopy, VLT-VISIR mid-IR spectroscopy and VLT-FORS2 optical spectroscopy. We studied the evolution of H2 and CO emission from hot and warm gas and Hα and forbidden line-emission during the initial outburst phase of V1647 Ori. Hα is observed in emission displaying P-Cygni profiles with blue-shifted absorption up to -700 km/s, suggesting the presence of a high velocity wind (Fig. 1a). [OI] emission at 6300 Å is observed displaying a blue-shifted emission shoulder, indicating the presence of material moving away from the star (Fig. 1b). We detect H2 1-0 S(1) and CO (P4 to P14 and P30-P38) ro-vibrational lines centered at the velocity of the star at all epochs (Fig. 1c & d). This strongly suggests that the H2 and CO emission originates from a disk and not from a warm outflow. The H2 1-0 S(0) and 2-1 S(1) ro-vibrational lines at 2.22 and 2.24 μm and the pure-rotational H2 0-0 S(1) and 0-0 S(2) lines at 17 and 12 μm were not detected in our spectra. Changes in the Hα and [OI] profiles and the H2 and CO emission observed do not correlate. We modeled the H2 and CO line profiles assuming emission from a flat disk in keplerian rotation with line intensity decreasing with radius (I ~ I0(R/Rmin)−α). We found that the disk of V1647 Ori is observed nearly face-on and that the line emission is produced within a fraction of an AU of the star (Fig. 1d

Baseline meniscal extrusion associated with incident knee osteoarthritis after 30 months in overweight and obese women

Objective: To investigate the association between baseline meniscal extrusion and the incidence of knee osteoarthritis (KOA) after 30 months in a high-risk population of overweight and obese women, free of clinical and radiological KOA at baseline. Methods: 407 middle-aged overweight women (body mass index - BMI ≥ 27 kg/m2) were evaluated at baseline and after 30 months of follow-up. Meniscal extrusion was defined as grade ≥2 on MRI according to MRI Osteoarthritis Knee Score (MOAKS). The primary outcome measure was KOA after 30 months follow-up, defined using the following criteria: either incidence of radiographic KOA (Kellgren & Lawrence grade 2 or higher), or clinical osteoarthritis (OA) according to the American College of Radiology (ACR) criteria, or medial or lateral joint space narrowing (JSN) of ≥1.0 mm. Using generalized estimating equations (GEE), we determined the association between knees with and without meniscal extrusion and both outcomes, corrected for the baseline differences. Results: 640 knees were available at baseline of which 24% (153) had meniscal extrusion. There was a significantly higher incidence of KOA according to the primary outcome measure in women with meniscal extrusion compared to those without extrusion (28.8%, odds ratio - OR 2.39, 95% CI 1.53, 3.73). A significantly higher incidence was found for the development of radiographic KOA (12.4%, OR 2.61, 95% CI 1.11, 6.13) and medial JSN (11.8%, OR 3.19, 95% CI 1.59, 6.41). Meniscal extrusion was not significantly associated with clinical KOA and lateral JSN. Conclusion: Meniscal extrusion was associated with a significantly higher incidence of KOA, providing an interesting target for early detection of individuals at risk for developing KOA