A Multi-Center Phase II Study (SAKK 36/06) of Single Agent Everolimus (RAD001) In Patients with Relapsed or Refractory Mantle Cell Lymphoma

Introduction: Mantle cell lymphoma (MCL) accounts for 6% of all B-cell lymphomas and remains incurable for most patients. Those who relapse after first line therapy or hematopoietic stem cell transplantation have a dismal prognosis with short response duration after salvage therapy. On a molecular level, MCL is characterised by the translocation t[11;14] leading to Cyclin D1 overexpression. Cyclin D1 is downstream of the mammalian target of rapamycin (mTOR) kinase and can be effectively blocked by mTOR inhibitors such as temsirolimus. We set out to define the single agent activity of the orally available mTOR inhibitor everolimus (RAD001) in a prospective, multi-centre trial in patients with relapsed or refractory MCL (NCT00516412). The study was performed in collaboration with the EU-MCL network. Methods: Eligible patients with histologically/cytologically confirmed relapsed (not more than 3 prior lines of systemic treatment) or refractory MCL received everolimus 10 mg orally daily on day 1 - 28 of each cycle (4 weeks) for 6 cycles or until disease progression. The primary endpoint was the best objective response with adverse reactions, time to progression (TTP), time to treatment failure, response duration and molecular response as secondary endpoints. A response rate of 10% was considered uninteresting and, conversely, promising if 30%. The required sample size was 35 pts using the Simon's optimal two-stage design with 90% power and 5% significance. Results: A total of 36 patients with 35 evaluable patients from 19 centers were enrolled between August 2007 and January 2010. The median age was 69.4 years (range 40.1 to 84.9 years), with 22 males and 13 females. Thirty patients presented with relapsed and 5 with refractory MCL with a median of two prior therapies. Treatment was generally well tolerated with anemia (11%), thrombocytopenia (11%), neutropenia (8%), diarrhea (3%) and fatigue (3%) being the most frequent complications of CTC grade III or higher. Eighteen patients received 6 or more cycles of everolimus treatment. The objective response rate was 20% (95% CI: 8-37%) with 2 CR, 5 PR, 17 SD, and 11 PD. At a median follow-up of 6 months, TTP was 5.45 months (95% CI: 2.8-8.2 months) for the entire population and 10.6 months for the 18 patients receiving 6 or more cycles of treatment. Conclusion: This study demonstrates that single agent everolimus 10 mg once daily orally is well tolerated. The null hypothesis of inactivity could be rejected indicating a moderate anti-lymphoma activity in relapsed/refractory MCL. Further studies of either everolimus in combination with chemotherapy or as single agent for maintenance treatment are warranted in MCL.

Approche multidisciptinaire des coûts humains des lombalgies [Human cost of low back pain: a multi-disciplinary approach]

The valuation of human costs is a necessity, but this task poses many problems of method. A team made of a philosopher, a psychologist and a physician has been working with economist researchers in order to look into the meaning that the preferences announced at the time of the inquiries on human costs by QALY methods could assume. These methods are often used to obtain a valuation of the impact of a health attack on people's quality of life. The methods--in the frame of the argument assumed by the economic theory on well-being--hypothesize that people's choices depend mainly on cognitive work. The qualitative interviews show that the psychological construction process for the announced preferences largely overlap this frame. In this paper the authors hastily tackle the factors which have an effect on the preferences. They conclude that the QALY methods don't seem to be able to assess the quality of life nori to valuate the damage that the quality of life could include.

North Iowa Juvenile Detention Services Commission, June 30, 2001 & June 30, 2002

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Central Iowa Juvenile Detention Center in Eldora Iowa, June 30, 2001 & June 30, 2002

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Central Iowa Juvenile Detention Center, June 30, 2003

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Kernel-based methods for change detection in remote sensing images

Nowadays, the joint exploitation of images acquired daily by remote sensing instruments and of images available from archives allows a detailed monitoring of the transitions occurring at the surface of the Earth. These modifications of the land cover generate spectral discrepancies that can be detected via the analysis of remote sensing images. Independently from the origin of the images and of type of surface change, a correct processing of such data implies the adoption of flexible, robust and possibly nonlinear method, to correctly account for the complex statistical relationships characterizing the pixels of the images. This Thesis deals with the development and the application of advanced statistical methods for multi-temporal optical remote sensing image processing tasks. Three different families of machine learning models have been explored and fundamental solutions for change detection problems are provided. In the first part, change detection with user supervision has been considered. In a first application, a nonlinear classifier has been applied with the intent of precisely delineating flooded regions from a pair of images. In a second case study, the spatial context of each pixel has been injected into another nonlinear classifier to obtain a precise mapping of new urban structures. In both cases, the user provides the classifier with examples of what he believes has changed or not. In the second part, a completely automatic and unsupervised method for precise binary detection of changes has been proposed. The technique allows a very accurate mapping without any user intervention, resulting particularly useful when readiness and reaction times of the system are a crucial constraint. In the third, the problem of statistical distributions shifting between acquisitions is studied. Two approaches to transform the couple of bi-temporal images and reduce their differences unrelated to changes in land cover are studied. The methods align the distributions of the images, so that the pixel-wise comparison could be carried out with higher accuracy. Furthermore, the second method can deal with images from different sensors, no matter the dimensionality of the data nor the spectral information content. This opens the doors to possible solutions for a crucial problem in the field: detecting changes when the images have been acquired by two different sensors.

North Iowa Juvenile Detention Services Commission, June 30, 2003

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A comparison between joint coordinate system and attitude vector for multi-segment foot kinematics.

The joint angles of multi-segment foot models have been primarily described using two mathematical methods: the joint coordinate system and the attitude vector. This study aimed to determine whether the angles obtained through these two descriptors are comparable, and whether these descriptors have similar sensitivity to experimental errors. Six subjects walked eight times on an instrumented walkway while the joint angles among shank, hindfoot, medial forefoot, and lateral forefoot were measured. The angles obtained using both descriptors and their sensitivity to experimental errors were compared. There was no overall significant difference between the ranges of motion obtained using both descriptors. However, median differences of more than 6° were noticed for the medial-lateral forefoot joint. For all joints and rotation planes, both descriptors provided highly similar angle patterns (median correlation coefficient: R>0.90), except for the medial-lateral forefoot angle in the transverse plane (median R=0.77). The joint coordinate system was significantly more sensitive to anatomical landmarks misplacement errors. However, the absolute differences of sensitivity were small relative to the joints ranges of motion. In conclusion, the angles obtained using these two descriptors were not identical, but were similar for at least the shank-hindfoot and hindfoot-medial forefoot joints. Therefore, the angle comparison across descriptors is possible for these two joints. Comparison should be done more carefully for the medial-lateral forefoot joint. Moreover, despite different sensitivities to experimental errors, the effects of the experimental errors on the angles were small for both descriptors suggesting that both descriptors can be considered for multi-segment foot models.

Selected Information About County Jails and Adult Detention Facilities in Iowa, 2003

During the 2002 session of the Iowa General Assembly, Senate File 2278 was enacted, establishing a new Section 356.36A within the Iowa Code. Subsequently, House File 2623 was enacted, which served to make a minor amendment to Senate File 2278. The Governor subsequently signed the amended legislation into law. The final version of the new Section 356.36A required that the Iowa Department of Human Rights, Division of Criminal and Juvenile Justice Planning and Statistical Analysis Center (CJJP) prepare a report for the Legislature “analyzing the confinement and detention needs of jails and facilities established pursuant to chapters 356 and 356A.

What the Law Requires: Accessible Multi-family Housing in Iowa, 2003

Booklet produced by the Iowa Civil Rights Commission for individuals who own, design, build, or develop multi-family housing.