Second malignancies in the context of lenalidomide treatment: an analysis of 2732 myeloma patients enrolled to the Myeloma XI trial.

We have carried out the largest randomised trial to date of newly diagnosed myeloma patients, in which lenalidomide has been used as an induction and maintenance treatment option and here report its impact on second primary malignancy (SPM) incidence and pathology. After review, 104 SPMs were confirmed in 96 of 2732 trial patients. The cumulative incidence of SPM was 0.7% (95% confidence interval (CI) 0.4-1.0%), 2.3% (95% CI 1.6-2.7%) and 3.8% (95% CI 2.9-4.6%) at 1, 2 and 3 years, respectively. Patients receiving maintenance lenalidomide had a significantly higher SPM incidence overall (P=0.011). Age is a risk factor with the highest SPM incidence observed in transplant non-eligible patients aged >74 years receiving lenalidomide maintenance. The 3-year cumulative incidence in this group was 17.3% (95% CI 8.2-26.4%), compared with 6.5% (95% CI 0.2-12.9%) in observation only patients (P=0.049). There was a low overall incidence of haematological SPM (0.5%). The higher SPM incidence in patients receiving lenalidomide maintenance therapy, especially in advanced age, warrants ongoing monitoring although the benefit on survival is likely to outweigh risk

Evaluation of flight efficiency for Stockholm Arlanda Airport arrivals

Analysis of punctuality of airport arrivals, as well as identification of causes of the delays within transition airspace, is an important step in evaluating performance of the Terminal Maneuvering Area (TMA) Air Navigation Services: without knowing the current performance levels, it is difficult to identify which areas could be improved. Deviations from the flight plans is one of the major reasons for arrival delays. In this work, we quantified the impact of the deviations from the flight plans on the fuel burn. One of the main reasons of fuel waste is non- optimal vertical profiles during the descent phase. We calculated how much extra fuel is wasted due to vertical flight inefficiency within Stockholm TMA.Peer ReviewedPostprint (published version

Neurons and neuronal activity control gene expression in astrocytes to regulate their development and metabolism

The influence that neurons exert on astrocytic function is poorly understood. To investigate this, we first developed a system combining cortical neurons and astrocytes from closely related species, followed by RNA-seq and in silico species separation. This approach uncovers a wide programme of neuron-induced astrocytic gene expression, involving Notch signalling, which drives and maintains astrocytic maturity and neurotransmitter uptake function, is conserved in human development, and is disrupted by neurodegeneration. Separately, hundreds of astrocytic genes are acutely regulated by synaptic activity via mechanisms involving cAMP/PKA-dependent CREB activation. This includes the coordinated activity-dependent upregulation of major astrocytic components of the astrocyte-neuron lactate shuttle, leading to a CREB-dependent increase in astrocytic glucose metabolism and elevated lactate export. Moreover, the groups of astrocytic genes induced by neurons or neuronal activity both show age-dependent decline in humans. Thus, neurons and neuronal activity regulate the astrocytic transcriptome with the potential to shape astrocyte-neuron metabolic cooperation

Comparative study of homocoupling reactions to create 2,2’-bipyridine adducts

The project focuses on investigating the synthesis of 2,2’-bipyridine adducts for potential future use as ligands in novel organometallic ruthenium complexes. The bipyridine building blocks, due to their excellent bidentate ligands with complexing abilities, will be incorporated into ruthenium complexes in a collaborative project, increasing the photosensitivity of these complexes, and opening the doors for many applications ranging from synthetic photovoltaics to anti-cancer activity.The first aim is to carry out a comparative study on the effects of electron donating substituents of variously substituted pyridines. The second aim is to compare the efficacy of two different palladium-based catalysts, namely, tetrakis (triphenylphosphine) palladium (0) and bis (triphenylphosphine) palladium (II) chloride, in order to optimize the preparation of these 2,2’-bipyridine adducts.To support the goal of the first aim, substrates 2-bromo-6-(1H-pyrazol-1-yl) pyridine, 2-bromo-3-hydroxypyridine, 2-bromo-4-methylpyridine, and 2-bromo-5-methylpyridine will be employed, to obtain the expected final adducts of 6,6’-(1H-pyrazol-1-yl)-2,2’-bipyridine, 2,2′-bipyridine-3,3′-diol, 4,4’-dimethyl-2,2’-bipyridine, and 5,5’-dimethyl-2,2’-bipyridine, respectively.To attain the second aim, reactions with all four substrates will be carried out utilizing both catalysts.Prior studies done in our lab have focused on optimizing the synthetic routes and have compared several homo and cross coupling reactions. It was determined that homocoupling offers a more efficient route than cross coupling, based on both the obtained product yield, as well as providing the desired symmetrical bipyridine adducts.The procedure for each reaction is conducted in an inert, moisture-free environment. First, the reaction chamber is assembled in a glovebox protecting the air-sensitive catalysts and substrates. The reaction chamber is then moved onto a Schlenk-line assembly, where an inert argon atmosphere is provided for the reactions to progress under. Reaction times vary from 12 to 72 hours based on the starting substrate, while the reaction progress is monitored with thin layer chromatography. Final products are isolated and purified via acidic extraction, and if needed recrystallization. Compound characterization is carried out utilizing NMR and FT-IR

Minimalist Sofa Redesign Using The Kano Method: Perancangan Ulang Sofa Minimalis Menggunakan Metode Kano

UKM Mebel Berkah Raya is a company engaged in the field of furniture, one of the products produced is Sofa products. The large number of competitors who are the company's competitors, makes it difficult for the products produced to compete with similar products on the market, therefore, the company conducts a preliminary survey involving loyal customers owned by UKM Mebel Berkah Raya, in order to find out the desires of customers for sofa products, especially sofa products that are produced by the UKM furniture, Berkah Raya. The results of this study are that the attributes that will be developed with the provisions of Attractive that produce customer satisfaction.attributes Indiffrent that can generate positive feedback with customers.attribute One-Dimantion can increase customer satisfaction. So that the resulting design in the form of an existing sofa design is representative of the measurements that have been carried out with the method used

Dynamics of PTH-induced disassembly of Npt2a/NHERF-1 complexes in living OK cells

Parathyroid hormone (PTH) inhibits the reabsorption of phosphate in the renal proximal tubule by disrupting the binding of the sodium-dependent phosphate transporter 2A (Npt2a) to the adapter protein sodium-hydrogen exchanger regulatory factor-1 (NHERF-1), a process initiated by activation of protein kinase C (PKC). To gain additional insights into the dynamic sequence of events, the time course of these responses was studied in living opossum kidney (OK) cells. Using a FRET-based biosensor, we found that PTH activated intracellular PKC within seconds to minutes. In cells expressing GFP-Npt2a and mCherry-NHERF, PTH did not affect the relative abundance of NHERF-1 but there was a significant and time-dependent decrease in the Npt2a/NHERF-1 ratio. The half-time to maximal dissociation was 15 to 20 min. By contrast, PTH had no effect on the fluorescence ratio for GFP-ezrin compared with mCherry-NHERF-1 at the apical surface. These experiments establish that PTH treatment of proximal tubule OK cells leads to rapid activation of PKC with the subsequent dissociation of Npt2a/NHERF-1 complexes. The association of NHERF-1 with Ezrin and their localization at the apical membrane, however, was unperturbed by PTH, thereby enabling the rapid recruitment and membrane reinsertion of Npt2a and other NHERF-1 targets on termination of the hormone response