Key Points• Long-term remissions after FCR chemoimmunotherapy in previously untreated patients with CLL.• Updated results on safety and efficacy of the CLL8 trial.Despite promising results with targeted drugs, chemoimmunotherapy with fludarabine, cyclophosphamide (FC), and rituximab (R) remains the standard therapy for fit patients with untreated chronic lymphocytic leukemia (CLL). Herein, we present the long-term follow-up of the randomized CLL8 trial reporting safety and efficacy of FC and FCR treatment of 817 treatment-naïve patients with CLL. The primary end point was progressionfree survival (PFS). With a median follow-up of 5.9 years, median PFS were 56.8 and 32.9 months for the FCR and FC group (hazard ratio [HR], 0.59; 95% confidence interval [CI], 0.50-0.69, P < .001). Median overall survival (OS) was not reached for the FCR group and was 86.0 months for the FC group (HR, 0.68; 95% CI, 0.54-0.89, P 5 .001). In patients with mutated IGHV (IGHV MUT), FCR improved PFS and OS compared with FC (PFS: HR, 0.47; 95% CI, 0.33-0.68, P < .001; OS: HR, 0.62; 95% CI, 0.34-1.11, P 5 .1). This improvement remained applicable for all cytogenetic subgroups other than del(17p). Long-term safety analyses showed that FCR had a higher rate of prolonged neutropenia during the first year after treatment (16.6% vs 8.8%; P 5 .007). Secondary malignancies including Richter's transformation occurred in 13.1% in the FCR group and in 17.4% in the FC group (P 5 .1). First-line chemoimmunotherapy with FCR induces long-term remissions and highly relevant improvement in OS in specific genetic subgroups of fit patients with CLL, in particular those with IGHV MUT. This trial was registered at www.clinicaltrials.gov as #NCT00281918. (Blood. 2016;127(2):208-215)

No abstract

No abstract

With the availability of high-resolution miniature spatial light modulators (SLMs) new methods in optical microscopy have become feasible. The SLMs discussed in this review consist of miniature liquid crystal displays with micronsized pixels that can modulate the phase and/or amplitude of an optical wavefront. In microscopy they can be used to control and shape the sample illumination, or they can act as spatial Fourier filters in the imaging path. Some of these applications are reviewed in this article. One of them, called spiral phase contrast, generates isotropic edge enhancement of thin phase samples or spiral-shaped interference fringes for thicker phase samples, which can be used to reconstruct the phase topography from a single on-axis interferogram. If SLMs are used for both illumination control and spatial Fourier filtering, this combination for instance allows for the generalization of the Zernike phase contrast principle. The new SLM-based approach improves the effective resolution and avoids some shortcomings and artifacts of the traditional method. The main advantage of SLMs in microscopy is their flexibility, as one can realize various operation modes in the same setup, without the need for changing any hardware components, simply by electronically switching the phase pattern displayed on the SLMs.

Purpose To determine the value of minimal residual disease (MRD) assessments, together with the evaluation of clinical response in chronic lymphocytic leukemia according to the 2008 International Workshop on Chronic Lymphocytic Leukemia criteria. Patients and Methods Progression-free survival (PFS) and overall survival of 554 patients from two randomized trials of the German CLL Study Group (CLL8: fludarabine and cyclophosphamide [FC] v FC plus rituximab; CLL10: FC plus rituximab v bendamustine plus rituximab) were analyzed according to MRD assessed in peripheral blood at a threshold of 10 and clinical response. The prognostic value of different parameters defining a partial response (PR) was further investigated. Results Patients with MRD-negative complete remission (CR), MRD-negative PR, MRD-positive CR, and MRD-positive PR experienced a median PFS from a landmark at end of treatment of 61 months, 54 months, 35 months, and 21 months, respectively. PFS did not differ significantly between MRD-negative CR and MRD-negative PR; however, PFS was longer for MRD-negative PR than for MRD-positive CR ( P = .048) and for MRD-positive CR compared with MRD-positive PR ( P = .002). Compared with MRD-negative CR, only patients with MRD-positive PR had a significantly shorter overall survival (not reached v 72 months; P = .001), whereas there was no detectable difference for patients with MRD-negative PR or MRD-positive CR ( P = 0.612 and P = 0.853, respectively). Patients with MRD-negative PR who presented with residual splenomegaly had only a similar PFS (63 months) compared with patients with MRD-negative CR (61 months; P = .354), whereas patients with MRD-negative PR with lymphadenopathy showed a shorter PFS (31 months; P < .001). Conclusion MRD quantification allows for improved PFS prediction in both patients who achive PR and CR, which thus supports its application in all responders. In contrast to residual lymphadenopathy, persisting splenomegaly does not impact outcome in patients with MRD-negative PR.

This file was dowloaded from the institutional repository Brage NIH -brage.bibsys.no/nih Nigg, B., Baltich, J., Maurer, C., Federolf, P. (2012) AbstractPrevious studies investigating the effects of shoe midsole hardness on running kinematics have often used male subjects from within a narrow age range. It is unknown whether shoe midsole hardness has the same kinematic effect on male and female runners as well as runners from different age categories. As sex and age have an effect on running kinematics, it is important to understand if shoe midsole hardness affects the kinematics of these groups in a similar fashion. However, current literature on the effects of sex and age on running kinematics are also limited to a narrow age range distribution in their study population. Therefore, this study tested the influence of three different midsole hardness conditions, sex and age on the lower extremity kinematics during heel-toe running. A comprehensive analysis approach was used to analyze the lower-extremity kinematic gait variables for 93 runners (male and female) aged 16-75 years. Participants ran at 3.33 ± 0.15 m/s on a 30 m-long runway with soft, medium and hard midsoles. A principal component analysis combined with a support vector machine showed that running kinematics based on shoe midsole hardness, sex, and age were separable and classifiable. Shoe midsole hardness demonstrated a subjectindependent effect on the kinematics of running. Additionally, it was found that age differences affected the more dominant movement components of running compared to differences due to the sex of a runner.

We present a fast and flexible non-interferometric method for the correction of small surface deviations on spatial light modulators, based on the Gerchberg-Saxton algorithm. The surface distortion information is extracted from the shape of a single optical vortex, which is created by the light modulator. The method can be implemented in optical tweezers systems for an optimization of trapping fields, or in an imaging system for an optimization of the point-spread-function of the entire image path.

No abstract