Fludarabine, cytarabine, granulocyte colony-stimulating factor, and idarubicin with gemtuzumab ozogamicin improves event-free survival in younger patients with newly diagnosed aml and overall survival in patients with npm1 and flt3 mutations

Purpose To determine the optimal induction chemotherapy regimen for younger adults with newly diagnosed AML without known adverse risk cytogenetics. Patients and Methods One thousand thirty-three patients were randomly assigned to intensified (fludarabine, cytarabine, granulocyte colony-stimulating factor, and idarubicin [FLAG-Ida]) or standard (daunorubicin and Ara-C [DA]) induction chemotherapy, with one or two doses of gemtuzumab ozogamicin (GO). The primary end point was overall survival (OS). Results There was no difference in remission rate after two courses between FLAG-Ida + GO and DA + GO (complete remission [CR] + CR with incomplete hematologic recovery 93% v 91%) or in day 60 mortality (4.3% v 4.6%). There was no difference in OS (66% v 63%; P = .41); however, the risk of relapse was lower with FLAG-Ida + GO (24% v 41%; P < .001) and 3-year event-free survival was higher (57% v 45%; P < .001). In patients with an NPM1 mutation (30%), 3-year OS was significantly higher with FLAG-Ida + GO (82% v 64%; P = .005). NPM1 measurable residual disease (MRD) clearance was also greater, with 88% versus 77% becoming MRD-negative in peripheral blood after cycle 2 (P = .02). Three-year OS was also higher in patients with a FLT3 mutation (64% v 54%; P = .047). Fewer transplants were performed in patients receiving FLAG-Ida + GO (238 v 278; P = .02). There was no difference in outcome according to the number of GO doses, although NPM1 MRD clearance was higher with two doses in the DA arm. Patients with core binding factor AML treated with DA and one dose of GO had a 3-year OS of 96% with no survival benefit from FLAG-Ida + GO. Conclusion Overall, FLAG-Ida + GO significantly reduced relapse without improving OS. However, exploratory analyses show that patients with NPM1 and FLT3 mutations had substantial improvements in OS. By contrast, in patients with core binding factor AML, outcomes were excellent with DA + GO with no FLAG-Ida benefit

Reducing the environmental impact of surgery on a global scale: systematic review and co-prioritization with healthcare workers in 132 countries

Abstract Background Healthcare cannot achieve net-zero carbon without addressing operating theatres. The aim of this study was to prioritize feasible interventions to reduce the environmental impact of operating theatres. Methods This study adopted a four-phase Delphi consensus co-prioritization methodology. In phase 1, a systematic review of published interventions and global consultation of perioperative healthcare professionals were used to longlist interventions. In phase 2, iterative thematic analysis consolidated comparable interventions into a shortlist. In phase 3, the shortlist was co-prioritized based on patient and clinician views on acceptability, feasibility, and safety. In phase 4, ranked lists of interventions were presented by their relevance to high-income countries and low–middle-income countries. Results In phase 1, 43 interventions were identified, which had low uptake in practice according to 3042 professionals globally. In phase 2, a shortlist of 15 intervention domains was generated. In phase 3, interventions were deemed acceptable for more than 90 per cent of patients except for reducing general anaesthesia (84 per cent) and re-sterilization of ‘single-use’ consumables (86 per cent). In phase 4, the top three shortlisted interventions for high-income countries were: introducing recycling; reducing use of anaesthetic gases; and appropriate clinical waste processing. In phase 4, the top three shortlisted interventions for low–middle-income countries were: introducing reusable surgical devices; reducing use of consumables; and reducing the use of general anaesthesia. Conclusion This is a step toward environmentally sustainable operating environments with actionable interventions applicable to both high– and low–middle–income countries

A systematic review of the quality of conduct and reporting of systematic reviews and meta-analyses in paediatric surgery

Objective: Our objective was to evaluate quality of conduct and reporting of published systematic reviews and meta-analyses in paediatric surgery. We also aimed to identify characteristics predictive of review quality. Background Systematic reviews summarise evidence by combining sources, but are potentially prone to bias. To counter this, the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) was published to aid in reporting. Similarly, the Assessing the Methodological Quality of Systematic Reviews (AMSTAR) measurement tool was designed to appraise methodology. The paediatric surgical literature has seen an increasing number of reviews over the past decade, but quality has not been evaluated. Methods: Adhering to PRISMA guidelines, we performed a systematic review with a priori design to identify systematic reviews and meta-analyses of interventions in paediatric surgery. From 01/2010 to 06/2016, we searched: MEDLINE, EMBASE, Cochrane, Centre for Reviews and Dissemination, Web of Science, Google Scholar, reference lists and journals. Two reviewers independently selected studies and extracted data. We assessed conduct and reporting using AMSTAR and PRISMA. Scores were calculated as the sum of reported items. We also extracted author, journal and article characteristics, and used them in exploratory analysis to determine which variables predict quality. Results: 112 articles fulfilled eligibility criteria (53 systematic reviews; 59 meta-analyses). Overall, 68% AMSTAR and 56.8% PRISMA items were reported adequately. Poorest scores were identified with regards a priori design, inclusion of structured summaries, including the grey literature, citing excluded articles and evaluating bias. 13 reviews were pre-registered and 6 in PRISMA-endorsing journals. The following predicted quality in univariate analysis:, word count, Cochrane review, journal h-index, impact factor, journal endorses PRISMA, PRISMA adherence suggested in author guidance, article mentions PRISMA, review includes comparison of interventions and review registration. The latter three variables were significant in multivariate regression. Conclusions: There are gaps in the conduct and reporting of systematic reviews in paediatric surgery. More endorsement by journals of the PRISMA guideline may improve review quality, and the dissemination of reliable evidence to paediatric clinicians

Studies on the Leukemogenesis of Mouse Leukemia by X-irradiation. Part 2. Classification of Leukemia and Various Factors Involved in Leukemogenesis.

For the elucidation of leukemogenesis of mouse leukemia induced by X-ray, a study was carried out on various factors influencing the development of leukemia. Namely, an effort was made to see the relationship between such factors as the age of mice receiving X-irradiation, the dose and the method of irradiation, the strain and sex of mice on one hand and the rate of leukemia induction on the other. Also a comparative study was made of the types of mouse leukemia elicited by X-ray. The results of the study are stated as follows. 1. In mice of the RF strain given one whole body X-irradiation of 350 r, and in both C(57)BL and C(3)Hf mice given four who1e body irradiations of 160 r each at the interval of 4 days to the total dosage of 600 r, the rate of leukemia induction was 77.3%, 88%, and 20% in the respective groups. 2. It has been demonstrated that the rate of leukemia induction was highest in mice of the RF strain 30-40 days old, and this rate decreased along with advancement in the age (several months old) of the mice. 3. As for the rate of leukemia induction in mice of the RF strain 30-40 days old, that received one whole body X-irradiation of 350 r, 22 (78.5%) out of 28 male mice developed leukemia while 19 (73.0%) out of 26 female mice, developed leukemia, showing no significant difference in sex. 4. It has been found that the rate of leukemia induction in the RF strain mice of 30-40 days old after one whole body X-irradiation increases with the dose of the irradiation, reaching its maximum at the dose of 350 r, but with the dose of 450 r the rate of leukemia induction rather decreases. 5. Of lymphocytic leukemia induced in the RF strain mice by X-irradiation, there were two types, that is, thymoma type and non-thymoma type, and there could be observed distinct differences in the peripheral blood pictures as well as in the patterns of cell infiltration into the liver between these two types. In addition, some of these lymphocytic leukemic mice presented a neutrophilic leukemoid reaction. There was only one mouse that developed myelogenous leukemia

LO phonon scattering as a depopulation mechanism in Si/SiGe quantum cascades

The linear optical phonon as a fast depopulation mechanism in Si/SiGe quantum cascade devices. Confirmed by pump-probe, the lifetime measurement is limited by the optical cycle of the source (<2 ps). Fourier transform spectroscopy shows intersubband electroluminescence with good agreement to theory

Silicon quantum cascade lasers for THz sources

This paper covers some recent advances in the search for a silicon quantum cascade laser. These include intersubband lifetime measurements, growth of high quality structures on buried suicide layers, and demonstration of THz electroluminescence

The acute physiological status of white sharks (Carcharodon carcharias) exhibits minimal variation after capture on SMART drumlines

Drumlines incorporating SMART (Shark-Management-Alert-in-Real-Time) technology are a new tool used in several bather protection programmes globally. In New South Wales (NSW), Australia, the white shark (Carcharodon carcharias) is a target species for SMART drumlines because they are often involved in attacks on humans. To understand white shark sensitivity to capture and to establish protocols around acceptable timeframes for responding to alerts, 47 juvenile and subadult white sharks were caught on SMART drumlines at five locations off the east coast of Australia. There was no at-vessel mortality during the sampling period. After capture, blood was sampled from each shark to assess its acute physiological status. Of the 18 metabolites investigated, only lactate and aspartate aminotransferase exhibited significant positive relationships with the capture duration on SMART drumlines. These results indicate that the capture process is relatively benign and that the current response times used here are appropriate to minimize long-term negative impacts on released white sharks. Where white sharks are likely to interact negatively with beachgoers, SMART drumlines can therefore be a useful addition to bather protection programmes that also aim to minimize harm to captured animals. Other shark species captured on SMART drumlines should also be investigated to gain broader understanding of potential physiological consequences of using this new technology