Wilms' tumor gene 1 (WT1) expression in childhood acute lymphoblastic leukemia:a wide range of WT1 expression levels, its impact on prognosis and minimal residual disease monitoring

Wilms' tumor gene 1 (WT1) is overexpressed in the majority (70-90%) of acute leukemias and has been identified as an independent adverse prognostic factor, a convenient minimal residual disease (MRD) marker and potential therapeutic target in acute leukemia. We examined WT1 expression patterns in childhood acute lymphoblastic leukemia (ALL), where its clinical implication remains unclear. Using a real-time quantitative PCR designed according to Europe Against Cancer Program recommendations, we evaluated WT1 expression in 125 consecutively enrolled patients with childhood ALL (106 BCP-ALL, 19 T-ALL) and compared it with physiologic WT1 expression in normal and regenerating bone marrow (BM). In childhood B-cell precursor (BCP)-ALL, we detected a wide range of WT1 levels (5 logs) with a median WT1 expression close to that of normal BM. WT1 expression in childhood T-ALL was significantly higher than in BCP-ALL (P<0.001). Patients with MLL-AF4 translocation showed high WT1 overexpression (P<0.01) compared to patients with other or no chromosomal aberrations. Older children (> or =10 years) expressed higher WT1 levels than children under 10 years of age (P<0.001), while there was no difference in WT1 expression in patients with peripheral blood leukocyte count (WBC) > or =50 x 10(9)/l and lower. Analysis of relapsed cases (14/125) indicated that an abnormal increase or decrease in WT1 expression was associated with a significantly increased risk of relapse (P=0.0006), and this prognostic impact of WT1 was independent of other main risk factors (P=0.0012). In summary, our study suggests that WT1 expression in childhood ALL is very variable and much lower than in AML or adult ALL. WT1, thus, will not be a useful marker for MRD detection in childhood ALL, however, it does represent a potential independent risk factor in childhood ALL. Interestingly, a proportion of childhood ALL patients express WT1 at levels below the normal physiological BM WT1 expression, and this reduced WT1 expression appears to be associated with a higher risk of relapse.

Exploiting evidence from unstructured data to enhance master data management

Master data management (MDM) integrates data from multiple
structured data sources and builds a consolidated 360-
degree view of business entities such as customers and products.
Today’s MDM systems are not prepared to integrate
information from unstructured data sources, such as news
reports, emails, call-center transcripts, and chat logs. However,
those unstructured data sources may contain valuable
information about the same entities known to MDM from
the structured data sources. Integrating information from
unstructured data into MDM is challenging as textual references
to existing MDM entities are often incomplete and
imprecise and the additional entity information extracted
from text should not impact the trustworthiness of MDM
data.
In this paper, we present an architecture for making MDM
text-aware and showcase its implementation as IBM InfoSphere
MDM Extension for Unstructured Text Correlation,
an add-on to IBM InfoSphere Master Data Management
Standard Edition. We highlight how MDM benefits from
additional evidence found in documents when doing entity
resolution and relationship discovery. We experimentally
demonstrate the feasibility of integrating information from
unstructured data sources into MDM.

Query Suggestions for Textual Problem Solution Repositories

Textual problem-solution repositories are available today in
various forms, most commonly as problem-solution pairs from community
question answering systems. Modern search engines that operate on
the web can suggest possible completions in real-time for users as they
type in queries. We study the problem of generating intelligent query
suggestions for users of customized search systems that enable querying
over problem-solution repositories. Due to the small scale and specialized
nature of such systems, we often do not have the luxury of depending on
query logs for finding query suggestions. We propose a retrieval model
for generating query suggestions for search on a set of problem solution
pairs. We harness the problem solution partition inherent in such
repositories to improve upon traditional query suggestion mechanisms
designed for systems that search over general textual corpora. We evaluate
our technique over real problem-solution datasets and illustrate that
our technique provides large and statistically significant

The TRAVATAN Dosing Aid accurately records when drops are taken.

PURPOSE:

To assess the accuracy of Travatan Dosing Aid recordings.

DESIGN:

Prospective evaluation of drop-recording accuracy.

METHODS:

Physicians and patients used the Dosing Aid, and logs of usage were compared to the data obtained from the Dosing Aid.

RESULTS:

Five physicians and 20 patients participated. Devices used by physicians recorded all drops dispensed. Extra readings were recorded when physicians carried the devices during the day. For patients, 93% of all drops were recorded, with 18 of 20 subjects having over 85% of the drops recorded. Seventy percent of patients would continue using the device.

CONCLUSIONS:

The Dosing Aid accurately recorded most eyedrops administered by patients and physicians. Given recent documentation of widespread under-compliance with medical therapy, the Dosing Aid could be a useful addition to clinical practice and research.

Time-resolved dosimetric verification of respiratory-gated radiotherapy exposures using a high-resolution 2D ionisation chamber array

The aim of this work was to track and verify the delivery of respiratory-gated irradiations, performed with three versions of TrueBeam linac, using a novel phantom arrangement that combined the OCTAVIUS® SRS 1000 array with a moving platform. The platform was programmed to generate sinusoidal motion of the array. This motion was tracked using the real-time position management (RPM) system and four amplitude gating options were employed to interrupt MV beam delivery when the platform was not located within set limits. Time-resolved spatial information extracted from analysis of x-ray fluences measured by the array was compared to the programmed motion of the platform and to the trace recorded by the RPM system during the delivery of the x-ray field. Temporal data recorded by the phantom and the RPM system were validated against trajectory log files, recorded by the linac during the irradiation, as well as oscilloscope waveforms recorded from the linac target signal. Gamma analysis was employed to compare time-integrated 2D x-ray dose fluences with theoretical fluences derived from the probability density function for each of the gating settings applied, where gamma criteria of 2%/2 mm, 1%/1 mm and 0.5%/0.5 mm were used to evaluate the limitations of the RPM system. Excellent agreement was observed in the analysis of spatial information extracted from the SRS 1000 array measurements. Comparisons of the average platform position with the expected position indicated absolute deviations of  <0.5 mm for all four gating settings. Differences were observed when comparing time-resolved beam-on data stored in the RPM files and trajectory logs to the true target signal waveforms. Trajectory log files underestimated the cycle time between consecutive beam-on windows by 10.0  ±  0.8 ms. All measured fluences achieved 100% pass-rates using gamma criteria of 2%/2 mm and 50% of the fluences achieved pass-rates  >90% when criteria of 0.5%/0.5 mm were used. Results using this novel phantom arrangement indicate that the RPM system is capable of accurately gating x-ray exposure during the delivery of a fixed-field treatment beam.