Use of the DirecNet Applied Treatment Algorithm (DATA) for diabetes management with a real-time continuous glucose monitor (the FreeStyle Navigator)

Background:  There are no published guidelines for use of real-time continuous glucose monitoring data by a patient; we therefore developed the DirecNet Applied Treatment Algorithm (DATA). The DATA provides algorithms for making diabetes management decisions using glucose values: (i) in real time which include the direction and rate of change of glucose levels, and (ii) retrospectively based on downloaded sensor data.
Objective:  To evaluate the use and effectiveness of the DATA in children with diabetes using a real-time continuous glucose sensor (the FreeStyle Navigator).
Subjects:  Thirty children and adolescents (mean ± standard deviation age = 11.2 ± 4.1 yr) receiving insulin pump therapy.
Methods:  Subjects were instructed on use of the DATA and were asked to download their Navigator weekly to review glucose patterns. An Algorithm Satisfaction Questionnaire was completed at 3, 7, and 13 wk.
Results:  At 13 wk, all of the subjects and all but one parent thought that the DATA gave good, clear directions for insulin dosing, and thought the guidelines improved their postprandial glucose levels. In responding to alarms, 86% of patients used the DATA at least 50% of the time at 3 wk, and 59% reported doing so at 13 wk. Similar results were seen in using the DATA to adjust premeal bolus doses of insulin.
Conclusions:  These results show the feasibility of implementing the DATA when real-time continuous glucose monitoring is initiated and support its use in future clinical trials of real-time continuous glucose monitoring.     

Photoprovocation in cutaneous lupus erythematosus: a multicenter study evaluating a standardized protocol

Photosensitivity is an important and distinguishing sign in various subtypes of cutaneous lupus erythematosus (CLE); however, it remains poorly defined. The purpose of this study was to evaluate whether standardized photoprovocation is a reproducible method to assess photosensitivity in subjects with CLE. A total of 47 subjects with CLE (subacute cutaneous lupus erythematosus (SCLE), n=14; discoid lupus erythematosus (DLE), n=20; lupus erythematosus tumidus (LET), n=13) and 13 healthy volunteers underwent photoprovocation at seven European sites. Of these, 22 (47%) subjects (57% SCLE, 35% DLE, and 54% LET) and none of the healthy volunteers developed photoprovoked lesions according to clinical analysis. Of these 22 subjects, 19 (86%) developed lesions that were histopathologically confirmed as specific for lupus erythematosus (LE). In CLE subjects who developed UV-induced lesions, 86% had Fitzpatrick's phototypes I or II, and the mean minimal erythema dose (MED) was significantly lower compared with subjects without UV-induced lesions (P=0.004). No significant differences in photoprovocation results were observed between study sites. Safety parameters showed no clinically meaningful differences between CLE subjects and healthy volunteers after photoprovocation. In conclusion, a standardized, safe, and reproducible protocol for photoprovocation using UVA and UVB radiation induced skin lesions in approximately half of all CLE subjects and showed comparable results across multiple sites. This method may therefore be used for future diagnostic testing and clinical trials.     

Jacob Heine (1800–1879)

Journal of Neurology -     

Phase I/II Study of Refametinib (BAY 86-9766) in Combination with Gemcitabine in Advanced Pancreatic cancer

Background

Activating KRAS mutations are reported in up to 90% of pancreatic cancers. Refametinib potently inhibits MEK1/2, part of the MAPK signaling pathway. This phase I/II study evaluated the safety and efficacy of refametinib plus gemcitabine in patients with advanced pancreatic cancer.

Methods

Phase I comprised dose escalation, followed by phase II expansion. Refametinib and gemcitabine plasma levels were analyzed for pharmacokinetics. KRAS mutational status was determined from circulating tumor DNA.

Results

Ninety patients overall received treatment. The maximum tolerated dose was refametinib 50 mg twice daily plus standard gemcitabine (1000 mg/m² weekly). The combination was well tolerated, with no pharmacokinetic interaction. Treatment-emergent toxicities included thrombocytopenia, fatigue, anemia, and edema. The objective response rate was 23% and the disease control rate was 73%. Overall response rate, disease control rate, progression-free survival, and overall survival were higher in patients without detectable KRAS mutations (48% vs. 28%, 81% vs. 69%, 8.8 vs. 5.3 months, and 18.2 vs. 6.6 months, respectively).

Conclusion

Refametinib plus gemcitabine was well tolerated, with a promising objective response rate, and had an acceptable safety profile and no pharmacokinetic interaction. There was a trend towards improved outcomes in patients without detectable KRAS mutations that deserves future investigation.

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A Study of Defects in InAs/GaSb Type-II Superlattices Using High-Resolution Reciprocal Space Mapping

In this paper, the study of defects in InAs/GaSb type-II superlattices using high-resolution an x-ray diffraction method as well as scanning (SEM) and transmission (TEM) electron microscopy is presented. The investigated superlattices had 200 (#SL200), 300 (#SL300), and 400 (#SL400) periods and were grown using molecular beam epitaxy. The growth conditions differed only in growth temperature, which was 370 °C for #SL400 and #SL200, and 390 °C for #SL300. A wings-like diffuse scattering was observed in reciprocal space maps of symmetrical (004) GaSb reflection. The micrometer-sized defect conglomerates comprised of stacking faults, and linear dislocations were revealed by the analysis of diffuse scattering intensity in combination with SEM and TEM imaging. The following defect-related parameters were obtained: (1) integrated diffuse scattering intensity of 0.1480 for #SL400, 0.1208 for #SL300, and 0.0882 for #SL200; (2) defect size: (2.5–3) μm × (2.5–3) μm –#SL400 and #SL200, (3.2–3.4) μm × (3.7–3.9) μm –#SL300; (3) defect diameter: ~1.84 μm –#SL400, ~2.45 μm –#SL300 and ~2.01 μm –#SL200; (4) defect density: 1.42 × 10⁶ cm⁻² –#SL400, 1.01 × 10⁶ cm⁻² –#SL300, 0.51 × 10⁶ cm⁻² –#SL200; (5) diameter of stacking faults: 0.14 μm and 0.13 μm for #SL400 and #SL200, 0.30 μm for #SL300.     

Numerical Methods for Solving the Hartree-Fock Equations of Diatomic Molecules II

In order to solve the partial differential equations that arise in the Hartree-Fock theory for diatomic molecules and in molecular theories that include electron correlation, one needs efficient methods for solving partial differential equations. In this article, we present numerical results for a two-variable model problem of the kind that arises when one solves the Hartree-Fock equations for a diatomic molecule. We compare results obtained using the spline collocation and domain decomposition methods with third-order Hermite splines to results obtained using the more-established finite difference approximation and the successive over-relaxation method. The theory of domain decomposition presented earlier is extended to treat regions that are divided into an arbitrary number of subregions by families of lines parallel to the two coordinate axes. While the domain decomposition method and the finite difference approach both yield results at the micro-Hartree level, the finite difference approach with a 9-point difference formula produces the same level of accuracy with fewer points. The domain decomposition method has the strength that it can be applied to problems with a large number of grid points. The time required to solve a partial differential equation for a fine grid with a large number of points goes down as the number of partitions increases. The reason for this is that the length of time necessary for solving a set of linear equations in each subregion is very much dependent upon the number of equations. Even though a finer partition of the region has more subregions, the time for solving the set of linear equations in each subregion is very much smaller. This feature of the theory may well prove to be a decisive factor for solving the two-electron pair equation, which – for a diatomic molecule – involves solving partial differential equations with five independent variables. The domain decomposition theory also makes it possible to study complex molecules by dividing them into smaller fragments thatare calculated independently. Since the domain decomposition approach makes it possible to decompose the variable space into separate regions in which the equations are solved independently, this approach is well-suited to parallel computing.