Imatinib-mesylate for all patients with hypereosinophilic syndrome?

Some recent papers have focused on the activity of imatinib-mesylate, a selective inhibitor of tyrosine kinase, in idiopathic hypereosinophilic syndrome (HES) [1], [2], [3] and [4]. In this setting, a possible therapeutic target was identified by Cools et al. [2], who described the fusion tyrosine-kinase gene FIP1L1/PDGFRA as the result of an interstitial deletion within chromosome 4 in nine out of sixteen (56%) patients affected by HES. Of interest, although in this study the response to imatinib was strictly correlated with the presence of FIP1L1/PDGFRA rearrangement (all patients with such a molecular lesion treated with imatinib responded), only five out of nine responding patients evidenced the abnormal transcript [2]. Among the possible alternative mechanisms for the activation of the PDGFRA tyrosine-kinase domain, these authors suggested there may be a different fusion gene

Smaller & Sooner: Exploiting High Magnetic Fields from New Superconductors for a More Attractive Fusion Energy Development Path

The current fusion energy development path, based on large volume moderate magnetic B field devices is proving to be slow and expensive. A modest development effort in exploiting new superconductor magnet technology development, and accompanying plasma physics research at high-B, could open up a viable and attractive path for fusion energy development. This path would feature smaller volume, fusion capable devices that could be built more quickly than low-to-moderate field designs based on conventional superconductors. Fusion’s worldwide development could be accelerated by using several small, flexible devices rather than relying solely on a single, very large device. These would be used to obtain the acknowledged science and technology knowledge necessary for fusion energy beyond achievement of high gain. Such a scenario would also permit the testing of multiple confinement configurations while distributing technical and scientific risk among smaller devices. Higher field and small size also allows operation away from well-known operational limits for plasma pressure, density and current. The advantages of this path have been long recognized—earlier US plans for burning plasma experiments (compact ignition tokamak, burning plasma experiment, fusion ignition research experiment) featured compact high-field designs, but these were necessarily pulsed due to the use of copper coils. Underpinning this new approach is the recent industrial maturity of high-temperature, high-field superconductor tapes that would offer a truly “game changing” opportunity for magnetic fusion when developed into large-scale coils. The superconductor tape form and higher operating temperatures also open up the possibility of demountable superconducting magnets in a fusion system, providing a modularity that vastly improves simplicity in the construction, maintenance, and upgrade of the coils and the internal nuclear engineering components required for fusion’s development. Our conclusion is that while tradeoffs exist in design choices, for example coil, cost and stress limits versus size, the potential physics and technology advantages of high-field superconductors are attractive and they should be vigorously pursued for magnetic fusion’s development

Demountable Toroidal Field Magnets for Use in a Compact Modular Fusion Reactor

A concept of demountable toroidal field magnets for a compact fusion reactor is discussed. The magnets generate a magnetic field of 9.2 T on axis, in a 3.3 m major radius tokamak. Subcooled YBCO conductors have a critical current density adequate to provide this large magnetic field, while operating at 20 K reduces thermodynamic cooling cost of the resistive electrical joints. Demountable magnets allow for vertical replacement and maintenance of internal components, potentially reducing cost and time of maintenance when compared to traditional sector maintenance. Preliminary measurements of contact resistance of a demountable YBCO electrical joint between are presented

Managing housing needs in post conflict housing reconstruction in Sri Lanka: gaps versus recommendations

Addressing housing needs in post conflict housing reconstruction leads to successful housing reconstruction. As part of a study of investigating how the housing needs can be effectively addressed in post conflict housing reconstruction, this paper identifies the gaps in managing housing needs in post conflict housing reconstruction within the context of Sri Lanka and presents the recommendations to minimise such gaps. Data was collected through un-structured interviews conducted with 37 participants, comprising policy makers, practitioners, academics and beneficiaries who engaged in post conflict housing reconstruction in Sri Lanka. Gaps were mainly found in conflict sensitivity, measures related to physical housing, performance of implementing agencies, policy and practice issues. On the job training, application of ‘do no harm’ principles, enhanced beneficiary participation, enhanced accountability, effective monitoring, enhanced knowledge sharing, adequate drinking water facilities, irrigation development and initiatives for material manufacturing were suggested as recommendations to minimise these gaps. Identification of gaps in managing housing needs in post conflict housing reconstruction and recommendations to minimise them inform policy makers to address the housing needs effectively through incorporating these aspects into the related policies. This in turn enhances the sustainability in housing development after conflicts

AGILE Observations of the Gravitational Wave Event GW150914

We report the results of an extensive search in the AGILE data for a gamma-ray counterpart of the LIGO gravitational wave event GW150914. Currently in spinning mode, AGILE has the potential of covering with its gamma-ray instrument 80 % of the sky more than 100 times a day. It turns out that AGILE came within a minute from the event time of observing the accessible GW150914 localization region. Interestingly, the gamma-ray detector exposed about 65 % of this region during the 100 s time intervals centered at -100 s and +300 s from the event time. We determine a 2-sigma flux upper limit in the band 50 MeV - 10 GeV, $UL = 1.9 \times 10^{-8} \rm \, erg \, cm^{-2} \, s^{-1}$ obtained about 300 s after the event. The timing of this measurement is the fastest ever obtained for GW150914, and significantly constrains the electromagnetic emission of a possible high-energy counterpart. We also carried out a search for a gamma-ray precursor and delayed emission over timescales ranging from minutes to days: in particular, we obtained an optimal exposure during the interval -150 / -30 s. In all these observations, we do not detect a significant signal associated with GW150914. We do not reveal the weak transient source reported by Fermi-GBM 0.4 s after the event time. However, even though a gamma-ray counterpart of the GW150914 event was not detected, the prospects for future AGILE observations of gravitational wave sources are decidedly promising.Comment: 20 pages, 6 figures. Submitted to the Astrophysical Journal Letters on April 1, 201

External validation of the preoperative Karakiewicz nomogram in a large multicentre series of patients with renal cell carcinoma

To perform a formal external validation of the preoperative Karakiewicz nomogram (KN) for the prediction of cancer-specific survival (CSS) using a large series of surgically treated patients diagnosed with organ-confined or metastatic renal cell carcinoma (RCC).Patient population originated from a series of retrospectively gathered cases that underwent radical or partial nephrectomy between years 1995 and 2007 for suspicion of kidney cancer. The original Cox coefficients were used to generate the predicted risk of CSS at 1, 2, 5, and 10 years following surgery and compared to the observed risk of CSS in the current population. External validation was quantified using measures of predictive accuracy, defined as model discrimination and calibration.A total of 3,374 patients were identified. Relative to the original development cohort, the current sample population had a larger proportion of patients with localized (40.0 vs. 26.3 \%, P < 0.001) and non-metastatic (92.2 vs. 88.1 \%, P = 0.03) disease at presentation. Model discrimination for the prediction of CSS was 87.8 \% (95 \% CI, 84.4-91.4) at 1 year, 87.0 \% (95 \% CI, 84.4-89.5) at 2 years, 84.7 \% (95 \% CI, 82.3-87.1) at 5 years, and 85.9 \% (95 \% CI, 83.2-88.6) at 10 years. The relationship between predicted and observed CSS risk was adequate in the calibration plot.The use of the KN for the prediction of CSS in patients diagnosed with renal cell carcinoma was validated in the current study. In consequence, this tool may be recommended for routine clinical counseling in patients with various stages of RCC in the preoperative setting