Background Relapsed or refractory diffuse large B-cell lymphoma (DLBCL) is an aggressive cancer with a median overall survival of less than 6 months. We aimed to assess the response to single-agent selinexor, an oral selective inhibitor of nuclear export, in patients with relapsed or refractory DLBCL who had no therapeutic options of potential clinical benefit. Methods SADAL was a multicentre, multinational, open-label, phase 2b study done in 59 sites in 19 countries. Patients aged 18 years or older with pathologically confirmed diffuse large B-cell lymphoma, an Eastern Cooperative Oncology Group performance status of 2 or less, who had received two to five lines of previous therapies, and progressed after or were not candidates for autologous stem-cell transplantation were enrolled. Germinal centre B-cell or non-germinal centre B-cell tumour subtype and double or triple expressor status were determined by immunohistochemistry and double or triple hit status was determined by cytogenetics. Patients received 60 mg selinexor orally on days 1 and 3 weekly until disease progression or unacceptable toxicity. The study was initially designed to evaluate both 60 mg and 100 mg twice-weekly doses of selinexor; however, the 100 mg dose was discontinued in the protocol (version 7.0) on March 29, 2017, when an improved therapeutic window was observed at 60 mg. Primary outcome was overall response rate. The primary outcome and safety were assessed in all patients who received 60 mg selinexor under protocol version 6.0, or enrolled under protocol versions 7.0 or higher and received at least one dose of selinexor. This trial is registered at ClinicalTrials.gov, NCT02227251 (active but not enrolling).

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Numerical heat transfer and fluid flow models have provided significant insight into welding processes and welded materials that could not have been achieved otherwise. However, the use of these models has been limited by two major problems. First, the model predictions do not always agree with the experimental results because some input parameters such as the arc efficiency cannot be accurately prescribed. Second, and more important, these models cannot determine multiple pathways or sets of welding variables that can lead to a particular weld attribute such as the weld pool geometry, which is defined by an equilibrium temperature surface. Here we show that the computational heat transfer and fluid flow models of fusion welding can overcome the aforementioned difficulties by combining with a genetic algorithm. The reliability of the convective heat transfer model can be significantly improved by optimizing the values of the uncertain input parameters from a limited volume of the experimental data. Furthermore, the procedure can calculate multiple sets of welding variables, each leading to the same weld geometry. These multiple paths were obtained via a global search using a genetic algorithm within the phenomenological framework of the equations of conservation of mass, momentum, and energy. This computational procedure was applied to the gas tungsten arc welding of Ti-6Al-4V alloy to calculate various sets of welding variables to achieve a specified weld geometry. The calculated sets of welding parameters showed wide variations of values. However, each set of welding parameters resulted in a specified geometry showing the effectiveness of the computational procedure.

related or recurring gene alterations were identified. In addition to the previously described IHC findings, 16 of 16 were positive for GATA3. Eleven patients with follow-up had no metastases or recurrent tumours. Recurrent tuberous sclerosis/MTOR pathway gene alterations in LOT support its consideration as a distinct morphological, immunohistochemical and genetic entity. PIK3CA is another pathway member that may be altered in these tumours. Further study will be necessary to determine whether tumour behaviour or syndromic associations differ from those of oncocytoma and chromophobe carcinoma, warranting different clinical consideration.

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