Profile of sapacitabine: potential for the treatment of newly diagnosed acute myeloid leukemia in elderly patients

Acute myeloid leukemia (AML) is a hematopoietic stem cell disorder that affects approximately 14,000 persons each year in the US. AML occurs at all ages but the incidence increases with age with the median age at diagnosis being 67 years. Advances in the treatment of AML over the past decades have led to improved survival, albeit mostly in younger patients. The prognosis of older patients with this disease over the same time span has not changed much and remains dismal. This review focuses on the epidemiology and characteristics of AML in elderly patients, the rationale for treating elderly AML patients, and the currently available and potential future treatment options such as sapacitabine. Elderly AML patients treated with intensive chemotherapy have a higher mortality rate, and a lower rate of complete remission and overall survival when compared to the younger population. This is due to both the different biology of the disease and the number of patient-specific factors. However, elderly AML patients treated with aggressive chemotherapy can achieve durable remissions, which offer prolonged survival and improved quality of life. Recent data also indicates that elderly AML patients deemed unfit for intensive chemotherapy benefit from leukemia-specific attenuated dose chemotherapy compared to supportive care alone. This has led to renewed interest to look for anti-leukemic therapies designed specifically for older patients. Sapacitabine, a novel oral nucleoside analog, promises good efficacy, favorable toxicity profile, and ease of administration; all of which makes it very appealing. Results from pre-clinical and clinical studies have been very encouraging and sapacitabine is currently being evaluated in a Phase III study, of which the results are eagerly awaited

A case study on mining social media data

In recent years, usage of social media websites have been soaring. This trend not only limits to personal but corporate web-sites. The latter platforms contain an enormous amount of data posted by customers or users. Without a surprise, the data in corporate social media web-sites are normally link to the products or services provided by the companies. Therefore, the data can be utilized for the sake of companies’ benefits. For example, operations management research and practice with the objective to make decisions on product and process design. Nevertheless, little has been done in this area. In this connection, this paper presents a case study to showcase how social media data can be exploited. A structured approach is proposed which involves the analysis of social media comments and a statistical cluster analysis to identify the inter-relationships among important factors

Solving Linear Coupled Fractional Differential Equations by Direct Operational Method and Some Applications

A new direct operational inversion method is introduced for solving coupled linear systems of ordinary fractional differential equations. The solutions so-obtained can be expressed explicitly in terms of multivariate Mittag-Leffler functions. In the case where the multiorders are multiples of a common real positive number, the solutions can be reduced to linear combinations of Mittag-Leffler functions of a single variable. The solutions can be shown to be asymptotically oscillatory under certain conditions. This technique is illustrated in detail by two concrete examples, namely, the coupled harmonic oscillator and the fractional Wien bridge circuit. Stability conditions and simulations of the corresponding solutions are given

Red blood cells and thrombin generation in sickle cell disease

The prothrombotic nature of sickle cell disease (SCD) is evidenced by the chronically elevated levels of almost all coagulation activation biomarkers, and an increased incidence of certain thrombotic events, including venous thromboembolism. Numerous studies have attempted to define the extent and elucidate the mechanism of the observed increase in thrombin generation in SCD patients in vivo. In general, these studies were performed using thrombin generation assays in platelet poor or platelet rich plasma and showed little difference in endogenous thrombin potential between the SCD cohort and healthy matched controls. In SCD, erythrocytes and monocytes have been demonstrated to exhibit procoagulant characteristics. Thus, the absence of these cellular components in standard thrombin generation assays may fail to reflect global hypercoagulability in the whole blood of patients with SCD. We were therefore surprised to see no difference in net thrombin generation in tissue factor-initiated initiated clotting of whole blood from patients with SCD. However, we are continuing to reconcile these seemingly disparate observations by slight modifications of the whole blood model that include alternative coagulation triggers and a re-examination of the net thrombin generation when the protein/protein S system is simultaneously interrogated

Improvement of Riboflavin Production Using Mineral Support in the Culture of Ashbya gossypii

Riboflavin production in a culture of Ashbya gossypii was enhanced by adding mineral support with adsorbed soybean oil. When the support in an amount of 1 % to the amount of medium was added into the culture at agitation intensity corresponding to impeller rotation rate of 600 rpm, the attained riboflavin concentration was 2.5 g/L at the culture time of 4 days, i.e. 1.6 times higher than that in the culture without adding mineral support. Riboflavin yield coefficient based on consumed substrate was also 1.6-fold higher than that in the culture without mineral support. In order to investigate the effect of mineral support on the riboflavin production and mycelial morphology variation, intracellular oil droplets were investigated by staining mycelia with Nile red. The A. gossypii cells, growing in submerged culture using soybean oil as a carbon source, were found to form intracellular micro-lipid bodies. The oil droplets became bigger as the culture time increased, and then the riboflavin leakage began, whereas lipid bodies gradually disappeared. When the soybean oil adsorbed on mineral support was added to the culture, the diameter of A. gossypii mycelia was much thicker and more riboflavin crystals were accumulated than in the pool of culture without mineral support; and what is more, mycelial autolysis was delayed for 2 days due to the presence of mineral support

Too Materialistic to Get Married and Have Children?

We developed new materials to induce a luxury mindset and activate materialistic values, and examined materialism's relationship to attitudes toward marriage and having children in Singapore. Path analyses indicated that materialistic values led to more negative attitudes toward marriage, which led to more negative attitudes toward children, which in turn led to a decreased number of children desired. Results across two studies highlight, at the individual level, the tradeoff between materialistic values and attitudes toward marriage and procreation and suggest that a consideration of psychological variables such as materialistic values may allow for a better understanding of larger-scale socioeconomic issues including low fertility rates among developed countries. We discuss implications and describe how psychological factors relating to low fertility fit within evolutionary mismatch and life history theory frameworks

Utilization of reduced graphene oxide/cadmium sulfide-modified carbon cloth for visible-light-prompt photoelectrochemical sensor for copper (II) ions

A newly developed CdS/rGO/CC electrode was prepared based on a flexible carbon cloth (CC) substrate with cadmium sulfide (CdS) nanoparticles and reduced graphene oxide (rGO). The CdS was synthesized using an aerosol-assisted chemical vapor deposition (AACVD) method, and the graphene oxide was thermally reduced on the modified electrode surface. The existence of rGO in the CdS-modified electrode increased the photocurrent intensity of the CdS/rGO/CC-modified electrode by three orders of magnitude, compared to that of the CdS/ITO electrode and two orders of magnitude higher than the CdS/CC electrode. A new visible-light-prompt photoelectrochemical sensor was developed based on the competitive binding reaction of Cu2+ and CdS on the electrode surface. The results showed that the effect of the Cu2+ on the photocurrent response was concentration-dependent over the linear ranges of 0.1–1.0 μM and 1.0–40.0 μM with a detection limit of 0.05 μM. The results of a selectivity test showed that this modified electrode has a high response toward Cu2+ compared to other heavy metal ions. The proposed CdS/rGO/CC electrode provided a significantly high potential current compared to other reported values, and could be a practical tool for the fast, sensitive, and selective determination of Cu2+

E.U. paediatric MOG consortium consensus: Part 4 - Outcome of paediatric myelin oligodendrocyte glycoprotein antibody-associated disorders

There is increasing knowledge on the role of antibodies against myelin oligodendrocyte glycoprotein (MOG-abs) in acquired demyelinating syndromes and autoimmune encephalitis in children. Better understanding and prediction of outcome is essential to guide treatment protocol decisions. Therefore, this part of the Paediatric European Collaborative Consensus provides an oversight of existing knowledge of clinical outcome assessment in paediatric MOG-ab-associated disorders (MOGAD). The large heterogeneity in disease phenotype, disease course, treatment and follow-up protocols is a major obstacle for reliable prediction of outcome. However, the clinical phenotype of MOGAD appears to be the main determinant of outcome. Patients with a transverse myelitis phenotype in particular are at high risk of accruing neurological disability (motor and autonomic), which is frequently severe. In contrast, having a single episode of optic neuritis any time during disease course is broadly associated with a lower risk of persistent disability. Furthermore, MOG-ab-associated optic neuritis often results in good functional visual recovery, although retinal axonal loss may be severe. The field of cognitive and behavioural outcome and epilepsy following demyelinating episodes has not been extensively explored, but in recent studies acute disseminated encephalomyelitis (-like) phenotype in the young children was associated with cognitive problems and epilepsy in long-term follow-up. In conclusion, main domains of importance in determining clinical outcome in paediatric MOGAD are visual, motor, autonomic and cognitive function. A standardised evaluation of these outcome domains in all children is of importance to allow adequate rehabilitation and follow-up

Guide to developing digital games for early grade literacy for developing countries

This guide works to assist game developers, literacy experts, and the staff of agencies interested in funding the development of digital games for early grade literacy learning. It presents information to be considered when designing games for literacy learning, and uses game examples that demonstrate how game developers and literacy educators have worked together. The guide has eight sections that address early grade reading and learning design considerations; design considerations for games development and learning; areas for research and development; case studies and supplemental resources