A Systematic Review and Network Meta-Analysis to Evaluate the Comparative Efficacy of Interventions for Unfit Patients with Chronic Lymphocytic Leukemia.

INTRODUCTION: Rituximab plus fludarabine and cyclophosphamide (RFC) is the standard of care for fit patients with untreated chronic lymphocytic leukemia (CLL); however, its use is limited in 'unfit' (co-morbid and/or full-dose F-ineligible) patients due to its toxicity profile. We conducted a systematic review and Bayesian network meta-analysis (NMA) to determine the relative efficacy of commercially available interventions for the first-line treatment of unfit CLL patients. METHODS: For inclusion in the NMA, studies had to be linked via common treatment comparators, report progression-free survival (PFS), and/or overall survival (OS), and meet at least one of the five inclusion criteria: median cumulative illness score >6, median creatinine clearance ≤70 mL/min, existing co-morbidities, median age ≥70 years, and no full-dose F in the comparator arm. A manual review, validated by external experts, of all studies that met at least one of these criteria was also performed to confirm that they evaluated first-line therapeutic options for unfit patients with CLL. RESULTS: In unfit patients, the main NMA (five studies for PFS and four for OS) demonstrated clear preference in terms of PFS for obinutuzumab + chlorambucil (G-Clb) versus rituximab + chlorambucil (R-Clb), ofatumumab + chlorambucil (O-Clb), fludarabine and chlorambucil (median hazard ratios [HRs] 0.43, 0.33, 0.20, and 0.19, respectively), and a trend for better efficacy versus rituximab + bendamustine (R-Benda) and RFC-Lite (median HR 0.81 and 0.88, respectively). OS results were generally consistent with PFS data, (median HR 0.48, 0.53, and 0.81, respectively) for G-Clb versus Clb, O-Clb, and R-Clb 0.35 and 0.81 versus F and R-Benda, respectively); however, the OS findings were associated with higher uncertainty. Treatment ranking reflected improved PFS and OS with G-Clb over other treatment strategies (median rank of one for both endpoints). CONCLUSION: G-Clb is likely to show superior efficacy to other treatment options selected in our NMA for unfit treatment-naïve patients with CLL. FUNDING: F. Hoffmann-La Roche Ltd

An improved 2D fem model for straight track corrugation using the mass redistribution method

In railway networks, rail corrugation remains a major problem which increases due to heavy traffic under urban conditions: various frictions, train dynamics, etc. But it is difficult to identify the real influence of each factor on both the onset and evolution of such defects on the strength of experiments alone. Thus it is very important to use numerical models to analyze corrugation defects. In this paper, we present an improvement of the finite element model to reproduce more realistically both the onset and evolution of straight track corrugation under transient conditions with the passage of multiple wheels. Furthermore, the application of finite element modeling to the rail-wheel contact problem is optimized by taking the mass redistribution method into account

Design of a tribometer for investigating tactile perception

12 pagesInternational audienceThe understanding of the tactile perception mechanism implies the reproduction and measurement of friction forces and vibrations induced by the contact between the skin of human fingers and object surfaces. When a finger moves to scan the surface of an object, it activates the receptors located under the skin allowing the brain to identify surfaces and information about their properties. The information concerning the object surface is affected by the forces and vibrations induced by the friction between the skin and the rubbed object. The vibrations propagate in the finger skin and are converted into electric impulses sent to the brain by the mechanoreceptors. Because of the low amplitude of the induced vibrations, it results quite hard to reproduce the tactile surface scanning and measuring it without affecting measurements by external noise coming from the experimental test-bench. In fact the reproduction of the sliding contact between two surfaces implies the relative motion between them, which is obtained by appropriate mechanisms having a more or less complicated kinematics and including several sliding surfaces (bearings, sliders, etc.). It results quite difficult to distinguish between the vibrations coming from the reproduced sliding and the parasitic noise coming from the other sliding contact pairs. This paper presents the design and validation of a tribometer, named TRIBOTOUCH, allowing for reproducing and measuring friction forces and friction induced vibrations that are basilar for a clear understanding of the mechanisms of the tactile sense

Effects of fertilisation on amino acid mobilisation by a plant-manipulating insect

National audience1. Phytophagous insects frequently manipulate their host-plant to improve their immediate environment. This generally implies substantial modifications of host metabolism, and sometimes an alteration of nitrogen allocation within the host-plant. However, the outcome of plant manipulation on amino acid or protein content can be modulated by environmental factors and host-plant traits. 2. It was investigated whether the pseudogall induced by the aphid Phloeomyzus passerinii (Signoret) (Aphididae: Phloeomyzinae) in the bark of its host-plant affects the amino acid content in bark tissues, and whether the strength of the modification is modulated by the fertilisation regime and/or the resistance level of the host-plant. The development of aphid colonies on a resistant and a susceptible poplar genotype, under three fertilisation regimes, was studied. After the development of colonies, the free and protein-bound amino acid content of the infested bark were quantified.3. Fertilisation enhanced poplar growth and increased the free amino acid content of bark tissues. Infestation also triggered accumulations of both free and protein-bound amino acids in the feeding sites, but in the susceptible genotype only. The increase in amino acid content was more pronounced when fertilisation was low, and fertilisation did not enhance aphid development.4. In conclusion, infestation by P. passerinii triggers an accumulation of amino acids, but the effect is influenced by both the fertilisation regime and the resistance level of the host-plant. This suggests that P. passerinii could affect the allocation of nutrients within trees during outbreaks

A Systematic Review and Network Meta-Analysis to Evaluate the Comparative Efficacy of Interventions for Unfit Patients with Chronic Lymphocytic Leukemia

<p><b>Article full text</b></p> <p><br></p> <p>The full text of this article can be found here<b>. </b><a href="https://link.springer.com/article/10.1007/s12325-016-0398-2">https://link.springer.com/article/10.1007/s12325-016-0398-2</a></p><p></p> <p><br> </p> <p><b>Provide enhanced content for this article</b></p> <p><br></p> <p>If you are an author of this publication and would like to provide additional enhanced content for your article then please contact <a href="http://www.medengine.com/Redeem/”mailto:[email protected]”"><b>[email protected]</b></a>.</p> <p><br></p> <p>The journal offers a range of additional features designed to increase visibility and readership. All features will be thoroughly peer reviewed to ensure the content is of the highest scientific standard and all features are marked as ‘peer reviewed’ to ensure readers are aware that the content has been reviewed to the same level as the articles they are being presented alongside. Moreover, all sponsorship and disclosure information is included to provide complete transparency and adherence to good publication practices. This ensures that however the content is reached the reader has a full understanding of its origin. No fees are charged for hosting additional open access content.</p> <p><br></p> <p>Other enhanced features include, but are not limited to:</p> <p><br></p> <p>• Slide decks</p> <p>• Videos and animations</p> <p>• Audio abstracts</p> <p>• Audio slides</p