关键词： Second generation tyrosine kinase inhibitor   Dasatinib   Nilotinib   Chronic phase chronic myeloid leukemia   Chronic myeloid leukemia   Switch  

摘要： While second generation tyrosine kinase inhibitors (2GTKIs) are highly effective therapies for chronic myeloid leukemia (CML), a significant minority of patients who initiate a 2GTKI will require a switch to an alternative TKI. The long-term outcomes of those who require a change in therapy after front-line 2GTKI therapy are largely undescribed. Here we describe the clinical outcomes associated with switch to an alternative TKI after first-line therapy with a 2GTKI. Of 232 patients who initiated a 2GTKI during the study period, 76 (33 %) switched to an alternative TKI. Reasons for switching included intolerance (79 %) and resistance (21 %). Among the 60 patients who switched due to intolerance, 53 (88 %) were able to achieve or maintain a major molecular response (MMR) with 5-year progression-free survival (PFS) 90.5 % (95 % CI 90.4-90.6 %). Amongst the 16 patients who switched due to resistance, 8 patients (50 %) were able to achieve MMR with 5-year PFS 80.4 % (95 % CI 80.2-80.6 %). Most patients who switched due to intolerance remained on their second-line TKI. Approximately 25 % of patients who initiate first-line 2GTKI in a real world setting will ultimately switch to an alternate TKI due to intolerance. Patients who switch for intolerance continue to enjoy excellent clinical outcomes.

关键词： Coronavirus disease 2019   MIS-C   Mesenchymal stem cell   Exosomes  

摘要： Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is a new type of coronavirus causing coronavirus 2019 (COVID-19) that was first observed in Wuhan, China, in Dec. 2019. An inflammatory immune response targeting children appeared during the pandemic, which was associated with COVID-19 named multisystem inflammatory syndrome in children (MIS-C). Characteristics of MIS-C include the classic inflammation findings, multi-organ dysfunction, and fever as the cardinal feature. Up to now, no specific therapy has been identified for MIS-C. Currently, considerable progress has been obtained in the MIS-C treatment by cell therapy, specially Mesenchymal stem cells (MSCs). Unique properties have been reported for MSCs, such as various resources for purification of cell, high proliferation, self-renewal, non-invasive procedure, tissue regenerator, multidirectional differentiation, and immunosuppression. As indicated by a recent clinical research, MSCs have the ability of reducing disease inflammation and severity in children with MIS-C. In the present review study, the benefits and characteristics of MSCs and exosomes are discussed for treating patients with MIS-C.

关键词： alternative medicine   complementary medicine   epidemiology  

摘要： Objective The aim of the study was to determine the prevalence and types of complementary and alternative medicine (CAM) use among pediatric emergency department (ED) patients and perceptions of CAM among the caregivers who administer CAM in Singapore. Methods A survey was administered in a Singapore ED (June 2016-June 2017). A convenience sample of parents/carers accompanying pediatric patients completed a self-administered questionnaire. The primary outcome measures were prevalence of CAM use and perceptions of CAM. Results Parents/carers of 610 patients participated. Four hundred seventy-five (78.0%, 95% confidence interval, 74.5-81.0) had taken a CAM within the previous 12 months and 110 (18.1%;95% confidence interval, 14.8-21.0) had taken a CAM on the day of presentation. There were no sex differences between CAM users and nonusers (P = 0.691). The use of CAM was more common among preschool children and younger (62.9%). There was no difference in CAM use among those with and without chronic disease (P = 0.878). Vitamins/supplements, cod liver oil, and probiotics were the most commonly used CAM. A total of 0.7% of CAM use was reported to the ED doctor. There were no adverse effects reported. The perception that CAMs are safe was more common among parents or caregivers who had administered CAM (P = 0.008). Conclusions Complementary and alternative medicine use is very common among pediatric ED patients in Singapore and is more prevalent than in Australia and the United Kingdom. However, it is not always reported to the doctor. Parents or caregivers who administer CAM are more likely to perceive CAMs to be safe.

关键词： Frequency-droop control   Frequency regulation   Operating reserve   Rotor speed control  

摘要： This paper proposes a frequency-droop control scheme for wind turbines using rotor speed control. The control scheme is proposed as a better alternative to conventional frequency-droop control techniques. When conventional frequency-droop control is used, the frequency response produced by the wind turbine is dependent on the method of power tracking employed. When power tracking is achieved using torque control, the wind turbine's frequency response is limited to short duration responses, even when operating reserve is available via de-loaded power tracking. This means that reserves cannot be fully utilised. When power tracking is achieved using power signal feedback, conventional frequency-droop methods under-deliver on the expected frequency-droop response due to rotor deceleration during frequency response. The proposed control scheme is unaffected by rotor deceleration and the method of power tracking employed as primary frequency regulation is achieved by varying the wind turbine's power tracking curve, rather than adding droop control signals to the wind turbine's power tracking reference. The effectiveness of the control scheme is validated through simulations using DIgSILENT PowerFactory. The results show that the control scheme produces the same frequency regulating response in wind turbines that achieve power tracking using torque control as those that use power signal feedback. This is an improvement on conventional frequency-droop control techniques and will improve the consistency and predictability of frequency regulating services procured from wind farms.

关键词： Psoas muscle index   Sarcopenia   Asian population   Trauma  

摘要： Background Sarcopenia has been shown to be an independent negative predictor in various diseases. The measurement of pre-defined criteria of skeletal muscle in patients with acute disease is usually unavailable. Therefore, we evaluate the psoas muscle area based on computed tomography (CT) imaging as an alternative for sarcopenia in an Asian trauma population. Methods 939 trauma patients were enrolled and had CT imaging performed primarily for trauma indications. The cross-sectional area of psoas muscle at the base of the fourth lumbar vertebral was measured on these CTs. Psoas muscle index (PMI) was calculated and analyzed to determine sex-specific cut-off values to define the "extremely low psoas muscle index" (ELPMI) group. Results Psoas muscle index was significantly higher in males (1065.09 +/- 230.51 mm(2)/m(2) in males vs 719.57 +/- 147.39 mm(2)/m(2) in females, p < 0.001) and decreased gradually with aging (p < 0.001). PMI of the subset of patients aged 18-40 (n = 462) weas analyzed to determine sex-specific cut-off values for ELPMI. PMI cut-off values for ELPMI (2 SD below mean) were 675 mm(2)/m(2) for males and 490 mm(2)/m(2) for females. The entire trauma cohort was further analyzed, and ELPMI was identified as an independent risk factor for a longer length of intensive unit stay (beta coefficient = 3.881, p = 0.011). Conclusion Data from young trauma adults were used to establish cut-off values for ELPMI, which is a longer ICU stay predictor. These cut-off values for ELPMI may apply to other acute disease entities.

关键词： Intramedullary nail   Intramedullary fixation   Fibula nailing   Fibula fracture   Ankle fracture   Lateral malleolus fracture   Minimal invasive surgery  

摘要： Purpose Despite the fact that open reduction and internal fixation with a plate, either non-locked or locked, is the standard of care for managing lateral malleolus fractures, intramedullary (IM) fixation of the fibula has been recently introduced as an alternative, mainly for some potential complicated situations. We hypothesized that almost all patterns of distal fibula fracture can be safely fixed with an IM device, with the potential benefit of providing biomechanical efficiency, but using a soft-tissue friendly implant. Here, we present a multicenter case series based on a proposed algorithm. Patients and methods Sixty-nine consecutive patients were managed with fibular IM fixation for closed malleolar fractures. Twenty patients were managed by IM screw fixation and 49 by fibular nailing. Outcome was measured both according to the American Orthopaedic Foot and Ankle Society (AOFAS) score for ankle and hindfoot, and the time to bone union. Results The mean AOFAS for Group I was 99.35 +/- 1.95 points and that for Group II was 89.30 +/- 16.98 points. There were no significant differences between the fracture pattern, according to the Lauge-Hansen classification, and post-operative levels of pain and functional activity among patients in both groups (p > 0.05). All fractures healed uneventfully in both groups. The mean time to union for Group I was 8.15 weeks and for Group II was 8.25 weeks (p > 0.05). Conclusion In this multicenter case series, intramedullary fixation for the lateral malleolus fracture presented itself as a viable and safe option for the treatment of almost all patterns of fibula fracture in adults. Overall, we were able to demonstrate the potential indications of the proposed algorithm for the choice of IM implant for the lateral malleolus fracture in terms of the Lauge-Hansen staged classification.

关键词： Acute kidney injury   Congenital heart disease   COVID-19   Diarrhea   MIS-C  

摘要： We present the case of a 3-month-old male infant patient who initially presented with severe dehydration with acute kidney injury secondary to COVID-19. Regarding the individual's previous history, the patient had congenital heart disease and was taking furosemide and captopril. The patient improved after initial hydration therapy. However, on the fourth day of hospitalization, the patient suddenly deteriorated and was found to have MIS-C. The patient's clinical course progressively worsened despite maximum support, and he died from severe MIS C. We conclude that during the COVID-19 period, MIS-C is a serious health problem that should be considered in the differential diagnosis of patients with acute kidney injury.

关键词： Five-equation model   Multi-component flows   Alternative WENO scheme   Stiffened gas EOS  

摘要： A fifth order finite difference alternative weighted essentially non-oscillatory scheme is studied for a five-equation model, which plays an important role in the modelling of compressible multi-component flows. In our algorithm, the primitive variables are used in the weighted essentially non-oscillatory interpolation, from which it can be proved that the equilibriums of the velocity and pressure are preserved respectively throughout the whole computation of contact moving interface problems, under the ideal and stiffened gases equations of state. In addition, it is found that with the interpolation being performed on the characteristic variables which are the projections of the primitive variables, non-physical oscillations appearing around the contact waves can be significantly restrained. Numerical examples verify the theory and illustrate the robustness of the proposed scheme.

关键词： Estimand   Last observation carried forward   Average response over time   Standardized area under the curve   Simple mean over time   Analysis of covariane   While on treatment strategy  

摘要： Missing data in longitudinal analysis has long been an important concern for drug developers and regulators. ICH published its E9 (R1) guidance in 2019, addressing the issue of estimands. In that guidance, five strategies are introduced. This manuscript focuses on the While on Treatment strategy, and attempts to propose average response over time as an alternative to last observation carried forward in the application of While on Treatment strategy. This is a simple summary statistics reflecting the average change a patient experiences during the trial. It is easy to interpret and easy to understand by non-statisticians. In clinical trials, with longitudinal data, average response over time has many applications. Two estimators are proposed to implement this estimand-simple mean over time, and standardized area under the curve (sAUC)

关键词： Phylogeography   Morphology   Marine worms   Annelids   Polychaete   Development  

摘要： Polychaetes belonging to the genus Capitella are known to represent a complex of opportunistic cryptic species that dominates the macrobenthos of organically enriched sediments, such as muddy areas particularly rich in sulfide. With the exception of the species, Capitella capitata (Fabricius) from West Greenland, Capitella spp. from the European Atlantic coast have never been accurately characterized both genetically and morphologically and were often reported as capitata in the literature. The life cycle of these European worms has not been described properly either, despite their widespread use as bio-indicators in ecological studies. The present study provides the first morphological description of Capitella specimens collected along the Brittany coast and the English Channel up to the entrance of the North Sea and their genetic diversification in this region. Both morphological and molecular data are congruent and support the co-occurrence of cryptic species at the tip of Brittany. The most frequent French mt lineages, C-Channel1, C-Atlantic and C-Channel2, although well distinct from Capitella teleta, are also divergent but closer to C. capitata initially described from Greenland. Following barcoding, the most abundant species (C-Channel1) was isolated and reared in the laboratory to describe its life cycle and predict both its dispersal ability and ecological success in the face of the sulfidic muddy habitats of the French harbors.