System quality, user satisfaction, and perceived net benefits of mobile broadband services

The continued decline of voice revenues is pushing mobile operators in Taiwan turn into data and content services for exploring new revenue opportunities and raising ARPU. This study aims to discuss the critical determinants of the internet user's adoption of 3.5G mobile broadband services in Taiwan. The theoretical framework employed in the study is Information System Success Model (DeLone & McLean, 2003; Chae et al.,2002), which is operationally defined with mobile web-services measurement scales. The study attempts to identify how the system quality of 3.5G mobile broadband services affects the customer satisfaction and their perceived net benefit. With the affordable mobile broadband connectivity, 3.5 G access or HSDPA in Taiwan has played a major role in the burgeoning mobile Internet market. HSDPA (High Speed Downlink Packet Access) could be viewed as an advanced version of WCDMA wireless network. HSDPA ideally provides mobile data services up to 14.4 Mbps for the downlinks and up to 5.8 Mbps for the uplinks. According to TWNIC, the number of cell phone subscribers in Taiwan has grown up to 23 million by March 2009 with a 100% penetration rate Yet, among cell phone subscribers there were only 1.6 million users adopting mobile broadband services. --Mobile Broadband Services,IS Success Model,Customer Satisfaction,Net Benefits

A Focus on Intermediate-Risk Acute Myeloid Leukemia: Sub-Classification Updates and Therapeutic Challenges

Simple Summary Risk stratification models, including the European LeukemiaNet 2017 and 2022 guidelines, categorize newly diagnosed acute myeloid leukemia (AML) patients into several subgroups of distinct genetic characteristics and disease outcomes. The intermediate-risk group remains the most heterogenous group, as most AML patients fall into it (i.e., a basket category) by virtue of not fulfilling criteria that identify specific entities (e.g., core-binding factor AML, TP53 mutations, complex karyotypes) of well-recognized prognostic significance. In this review, we aim to discuss the latest updates on intermediate-risk definition and highlight the therapeutic advances and challenges that warrant refining the prognostic classification of this category. Acute myeloid leukemia (AML) represents a heterogeneous group of hematopoietic neoplasms deriving from the abnormal proliferation of myeloid progenitors in the bone marrow. Patients with AML may have highly variable outcomes, which are generally dictated by individual clinical and genomic characteristics. As such, the European LeukemiaNet 2017 and 2022 guidelines categorize newly diagnosed AML into favorable-, intermediate-, and adverse-risk groups, based on their molecular and cytogenetic profiles. Nevertheless, the intermediate-risk category remains poorly defined, as many patients fall into this group as a result of their exclusion from the other two. Moreover, further genomic data with potential prognostic and therapeutic influences continue to emerge, though they are yet to be integrated into the diagnostic and prognostic models of AML. This review highlights the latest therapeutic advances and challenges that warrant refining the prognostic classification of intermediate-risk AML

Effects Of Dry Oxidation Treaments On The Characteristics Of Gallium Oxide Thin Films Prepared Using Sol-Gel Spin Coating Method

In this paper, gallium oxide (Ga2O3) thin films were grown on silicon (Si) substrate using a relatively simple and low-cost sol-gel spin coating method followed dry oxidation process. Two series of dry oxidation experiments were conducted, i.e., (i) annealing at different oxygen flow rates (i.e., from 2 L/min – 5 L/min) under 1100°C, and (ii) annealing at oxygen flow rate of 5 L/min under different temperatures (i.e., from 800°C to 1100°C). The effects of the oxygen gas flow rates under different temperatures on the structural, surface morphology, and optical properties of the deposited films were investigated. All results revealed that crystalline Ga2O3 layers were formed. From the X-ray diffraction results, all deposited films exhibit two prominent diffraction peaks corresponding to the Ga2O3 (1 ̅10) and (002). The annealing at different temperatures experiments showed that the surface roughness and the grains size increased as the temperature increases from 800°C to 1100°C. The optical band gap energy of the deposited films was extracted from the Ultraviolet-violet transmission spectra. This obtained energy bandgap is within the ranges of 4.69 – 4.83 eV, i.e., in reasonable agreement with the reported values. In summary, all the results showed that polycrystalline Ga2O3thin films were able to be grown on p-Si (100) substrate through the proposed methodology. While the best conditions for the dry oxidation process are at the oxygen flowrate of 5 L/min at temperature of 1100o C

Selective inhibition of FLT3 by gilteritinib in relapsed or refractory acute myeloid leukaemia: a multicentre, first-in-human, open-label, phase 1-2 study.

BackgroundInternal tandem duplication mutations in FLT3 are common in acute myeloid leukaemia and are associated with rapid relapse and short overall survival. The clinical benefit of FLT3 inhibitors in patients with acute myeloid leukaemia has been limited by rapid generation of resistance mutations, particularly in codon Asp835 (D835). We aimed to assess the highly selective oral FLT3 inhibitor gilteritinib in patients with relapsed or refractory acute myeloid leukaemia.MethodsIn this phase 1-2 trial, we enrolled patients aged 18 years or older with acute myeloid leukaemia who either were refractory to induction therapy or had relapsed after achieving remission with previous treatment. Patients were enrolled into one of seven dose-escalation or dose-expansion cohorts assigned to receive once-daily doses of oral gilteritinib (20 mg, 40 mg, 80 mg, 120 mg, 200 mg, 300 mg, or 450 mg). Cohort expansion was based on safety and tolerability, FLT3 inhibition in correlative assays, and antileukaemic activity. Although the presence of an FLT3 mutation was not an inclusion criterion, we required ten or more patients with locally confirmed FLT3 mutations (FLT3mut+) to be enrolled in expansion cohorts at each dose level. On the basis of emerging findings, we further expanded the 120 mg and 200 mg dose cohorts to include FLT3mut+ patients only. The primary endpoints were the safety, tolerability, and pharmacokinetics of gilteritinib. Safety and tolerability were assessed in the safety analysis set (all patients who received at least one dose of gilteritinib). Responses were assessed in the full analysis set (all patients who received at least one dose of study drug and who had at least one datapoint post-treatment). Pharmacokinetics were assessed in a subset of the safety analysis set for which sufficient data for concentrations of gilteritinib in plasma were available to enable derivation of one or more pharmacokinetic variables. This study is registered with ClinicalTrials.gov, number NCT02014558, and is ongoing.FindingsBetween Oct 15, 2013, and Aug 27, 2015, 252 adults with relapsed or refractory acute myeloid leukaemia received oral gilteritinib once daily in one of seven dose-escalation (n=23) or dose-expansion (n=229) cohorts. Gilteritinib was well tolerated; the maximum tolerated dose was established as 300 mg/day when two of three patients enrolled in the 450 mg dose-escalation cohort had two dose-limiting toxicities (grade 3 diarrhoea and grade 3 elevated aspartate aminotransferase). The most common grade 3-4 adverse events irrespective of relation to treatment were febrile neutropenia (97 [39%] of 252), anaemia (61 [24%]), thrombocytopenia (33 [13%]), sepsis (28 [11%]), and pneumonia (27 [11%]). Commonly reported treatment-related adverse events were diarrhoea (92 [37%] of 252]), anaemia (86 [34%]), fatigue (83 [33%]), elevated aspartate aminotransferase (65 [26%]), and increased alanine aminotransferase (47 [19%]). Serious adverse events occurring in 5% or more of patients were febrile neutropenia (98 [39%] of 252; five related to treatment), progressive disease (43 [17%]), sepsis (36 [14%]; two related to treatment), pneumonia (27 [11%]), acute renal failure (25 [10%]; five related to treatment), pyrexia (21 [8%]; three related to treatment), bacteraemia (14 [6%]; one related to treatment), and respiratory failure (14 [6%]). 95 people died in the safety analysis set, of which seven deaths were judged possibly or probably related to treatment (pulmonary embolism [200 mg/day], respiratory failure [120 mg/day], haemoptysis [80 mg/day], intracranial haemorrhage [20 mg/day], ventricular fibrillation [120 mg/day], septic shock [80 mg/day], and neutropenia [120 mg/day]). An exposure-related increase in inhibition of FLT3 phosphorylation was noted with increasing concentrations in plasma of gilteritinib. In-vivo inhibition of FLT3 phosphorylation occurred at all dose levels. At least 90% of FLT3 phosphorylation inhibition was seen by day 8 in most patients receiving a daily dose of 80 mg or higher. 100 (40%) of 249 patients in the full analysis set achieved a response, with 19 (8%) achieving complete remission, ten (4%) complete remission with incomplete platelet recovery, 46 (18%) complete remission with incomplete haematological recovery, and 25 (10%) partial remission INTERPRETATION: Gilteritinib had a favourable safety profile and showed consistent FLT3 inhibition in patients with relapsed or refractory acute myeloid leukaemia. These findings confirm that FLT3 is a high-value target for treatment of relapsed or refractory acute myeloid leukaemia; based on activity data, gilteritinib at 120 mg/day is being tested in phase 3 trials.FundingAstellas Pharma, National Cancer Institute (Leukemia Specialized Program of Research Excellence grant), Associazione Italiana Ricerca sul Cancro

Delivery of an Ebola Virus-Positive Stillborn Infant in a Rural Community Health Center, Sierra Leone, 2015.

We report the case of an Ebola virus (EBOV) RNA-negative pregnant woman who delivered an EBOV RNA-positive stillborn infant at a community health center in rural Sierra Leone, 1 month after the mother's last possible exposure. The mother was later found to be immunoglobulins M and G positive indicating previous infection. The apparent absence of Ebola symptoms and not recognizing that the woman had previous contact with an Ebola patient led health workers performing the delivery to wear only minimal personal protection, potentially exposing them to a high risk of EBOV infection. This case emphasizes the importance of screening for epidemiological risk factors as well as classic and atypical symptoms of Ebola when caring for pregnant women, even once they have passed the typical time frame for exposure and incubation expected in nonpregnant adults. It also illustrates the need for health-care workers to use appropriate personal protection equipment when caring for pregnant women in an Ebola setting

A phase 1/2 study of the oral FLT3 inhibitor pexidartinib in relapsed/refractory FLT3-ITD-mutant acute myeloid leukemia.

FMS-like tyrosine kinase 3 (FLT3) tyrosine kinase inhibitors (TKIs) have activity in acute myeloid leukemia (AML) patients with FLT3 internal tandem duplication (ITD) mutations, but efficacy is limited by resistance-conferring kinase domain mutations. This phase 1/2 study evaluated the safety, tolerability, and efficacy of the oral FLT3 inhibitor PLX3397 (pexidartinib), which has activity against the FLT3 TKI-resistant F691L gatekeeper mutation in relapsed/refractory FLT3-ITD-mutant AML. Ninety patients were treated: 34 in dose escalation (part 1) and 56 in dose expansion (part 2). Doses of 800 to 5000 mg per day in divided doses were tested. No maximally tolerated dose was reached. Plasma inhibitory assay demonstrated that patients dosed with ≥3000 mg had sufficient levels of active drug in their trough plasma samples to achieve 95% inhibition of FLT3 phosphorylation in an FLT3-ITD AML cell line. Based on a plateau in drug exposure, the 3000-mg dose was chosen as the recommended phase 2 dose. The most frequently reported treatment-emergent adverse events were diarrhea (50%), fatigue (47%), and nausea (46%). Based on modified response criteria, the overall response rate to pexidartinib among all patients was 21%. Twenty-three percent of patients treated at ≥2000 mg responded. The overall composite complete response rate for the study was 11%. Six patients were successfully bridged to transplantation. Median overall survival (OS) of patients treated in dose expansion was 112 days (90% confidence interval [CI], 77-150 days), and median OS of responders with complete remission with or without recovery of blood counts was 265 days (90% CI, 170-422 days). This trial was registered at www.clinicaltrials.gov as #NCT01349049

A simple DNA stretching method for fluorescence imaging of single DNA molecules

Stretching or aligning DNA molecules onto a surface by means of molecular combing techniques is one of the critical steps in single DNA molecule analysis. However, many of the current studies have focused on λ-DNA, or other large DNA molecules. There are very few studies on stretching methodologies for DNA molecules generated via PCR (typically smaller than 20 kb). Here we describe a simple method of stretching DNA molecules up to 18 kb in size on a modified glass surface. The very low background fluorescence allows efficient detection of single fluorescent dye labels incorporated into the stretched DNA molecules

Delayed Contrast Enhancement Imaging of a Murine Model for Ischemia Reperfusion with Carbon Nanotube Micro-CT

We aim to demonstrate the application of free-breathing prospectively gated carbon nanotube (CNT) micro-CT by evaluating a myocardial infarction model with a delayed contrast enhancement technique. Evaluation of murine cardiac models using micro-CT imaging has historically been limited by extreme imaging requirements. Newly-developed CNT-based x-ray sources offer precise temporal resolution, allowing elimination of physiological motion through prospective gating. Using free-breathing, cardiac-gated CNT micro-CT, a myocardial infarction model can be studied non-invasively and with high resolution. Myocardial infarction was induced in eight male C57BL/6 mice aged 8–12 weeks. The ischemia reperfusion model was achieved by surgically occluding the LAD artery for 30 minutes followed by 24 hours of reperfusion. Tail vein catheters were placed for contrast administration. Iohexol 300mgI/mL was administered followed by images obtained in diastole. Iodinated lipid blood pool contrast agent was then administered, followed with images at systole and diastole. Respiratory and cardiac signals were monitored externally and used to gate the scans of free-breathing subjects. Seven control animals were scanned using the same imaging protocol. After imaging, the heart was harvested, cut into 1mm slices and stained with TTC. Post-processing analysis was performed using ITK-Snap and MATLAB. All animals demonstrated obvious delayed contrast enhancement in the left ventricular wall following the Iohexol injection. The blood pool contrast agent revealed significant changes in cardiac function quantified by 3-D volume ejection fractions. All subjects demonstrated areas of myocardial infarct in the LAD distribution on both TTC staining and micro-CT imaging. The CNT micro-CT system aids straightforward, free-breathing, prospectively-gated 3-D murine cardiac imaging. Delayed contrast enhancement allows identification of infarcted myocardium after a myocardial ischemic event. We demonstrate the ability to consistently identify areas of myocardial infarct in mice and provide functional cardiac information using a delayed contrast enhancement technique

Quality of life and well-being problems in secondary schoolgirls in Kenya: Prevalence, associated characteristics, and course predictors

Background: Adolescents in sub-Saharan Africa often report low levels of quality of life (QoL) and well-being, but reliable data are limited. This study examines which sociodemographic, health, and behavioral risk factors and adverse adolescent experiences are associated with, and predictive of, QoL in Kenyan secondary schoolgirls. Methods and findings: 3,998 girls at baseline in a randomised controlled trial in Siaya County, western Kenya were median age 17.1 years. Subjectively perceived physical, emotional, social and school functioning was assessed using the Pediatric Quality of Life (QoL) Inventory-23. Laboratory-confirmed and survey data were utilized to assess sociodemographic, health and behavioral characteristics, and adverse adolescent experiences. We identified a group of girls with Low QoL (n=1126; 28.2%), Average QoL (n=1445; 36.1%); and High QoL (n=1427; 35.7%). Significantly higher scores on all well-being indicators in the LQoL compared with HQoL group indicated good construct validity (Odds Ratio's (ORs) varying from 3.31 (95% CI:2.41-4.54, p<.001) for feeling unhappy at home to 11.88 (95%CI:7.96-17.74, p< .001) for PHQ9 defined possible caseness (probable diagnosis) of depression. Adverse adolescent experiences were independently statistically significant in the LQoL compared to the HQoL group for threats of family being hurt (aOR=1.35,1.08-1.68, p=.008), sexual harassment out of school (aOR=2.17,1.79-2.64, p<.001), and for menstrual problems like unavailability of sanitary pads (aOR=1.23,1.05-1.44, p=.008) and stopping activities due to menstruation (aOR=1.77,1.41-2.24, p<.001). After 2-years follow-up of 906 girls in the LQoL group, 22.7% persisted with LQoL. Forced sex (aOR=1.56,1.05-2.32, p=.028) and threats of family being hurt (aOR=1.98,1.38-2.82, p<.001) were independent predictors of persistent LQoL problems. Conclusions: Persistent QoL problems in Kenyan adolescent girls are associated with adverse physical, sexual and emotional experiences and problems with coping with their monthly menstruation. A multi-factorial integral approach to reduce the rate of adverse adolescent experiences is needed, including provision of menstrual hygiene products