1,538 research outputs found
Phase II study of cabazitaxel as second-third line treatment in patients with metastatic adrenocortical carcinoma
Adjuvant platinum-based chemotherapy in radically resected adrenocortical carcinoma: a cohort study
S-GRAS score for prognostic classification of adrenocortical carcinoma: an international, multicenter ENSAT study
Forced response prediction of turbine blades with flexible dampers: the impact of engineering modelling choices
This paper focuses on flexible friction dampers (or “strips”) mounted on the underside of adjacent turbine blade platforms for sealing and damping purposes. A key parameter to ensure a robust and trustworthy design is the correct prediction of the maximum frequency shift induced by the strip damper coupling adjacent blades. While this topic has been extensively addressed on rigid friction dampers, both experimentally and numerically, no such investigation is available as far as flexible dampers are concerned. This paper builds on the authors’ prior experience with rigid dampers to investigate the peculiarities and challenges of a robust dynamic model of blade-strips systems. The starting point is a numerical tool implementing state-of-the-art techniques for the efficient solution of the nonlinear equations, e.g., multi-harmonic balance method with coupled static solution and state-of-the-art contact elements. The full step-by-step modelling process is here retraced and upgraded to take into account the damper flexibility: for each step, key modelling choices (e.g., mesh size, master nodes selection, contact parameters) which may affect the predicted response are addressed. The outcome is a series of guidelines which will help the designer assign numerical predictions the proper level of trust and outline a much-needed experimental campaign
The Determinants of HIV Treatment Costs in Resource Limited Settings
Background: Governments and international donors have partnered to provide free HIV treatment to over 6 million individuals in low and middle-income countries. Understanding the determinants of HIV treatment costs will help improve efficiency and provide greater certainty about future resource needs. Methods and Findings: We collected data on HIV treatment costs from 54 clinical sites in Botswana, Ethiopia, Mozambique, Nigeria, Uganda, and Vietnam. Sites provided free HIV treatment funded by the U.S. President’s Emergency Plan for AIDS Relief (PEPFAR), national governments, and other partners. Service delivery costs were categorized into successive six-month periods from the date when each site began HIV treatment scale-up. A generalized linear mixed model was used to investigate relationships between site characteristics and per-patient costs, excluding ARV expenses. With predictors at their mean values, average annual per-patient costs were 353 (255–468) for adult patients in the first 6 months of ART, and $222 (161–296) for adult patients on ART for >6 months (excludes ARV costs). Patient volume (no. patients receiving treatment) and site maturity (months since clinic began providing treatment services) were both strong independent predictors of per-patient costs. Controlling for other factors, costs declined by 43% (18–63) as patient volume increased from 500 to 5,000 patients, and by 28% (6–47) from 5,000 to 10,000 patients. For site maturity, costs dropped 41% (28–52) between months 0–12 and 25% (15–35) between months 12–24. Price levels (proxied by per-capita GDP) were also influential, with costs increasing by 22% (4–41) for each doubling in per-capita GDP. Additionally, the frequency of clinical follow-up, frequency of laboratory monitoring, and clinician-patient ratio were significant independent predictors of per-patient costs. Conclusions: Substantial reductions in per-patient service delivery costs occur as sites mature and patient cohorts increase in size. Other predictors suggest possible strategies to reduce per-patient costs
adjuvant mitotane for adrenocortical cancer working through uncertainty
The Journal of Clinical Endocrinology & Metabolism recently published a commentary by Huang and Fojo (1) offering a skeptical view on the efficacy of mitotane as an adjunctive postsurgical measure in patients with adrenocortical cancer (ACC). Their commentary focused on outlining the limitations of our recent study which indicated that adjuvant mitotane may prolong recurrence-free survival (RFS) in patients with radically resected ACC (2). However, we do not agree with several of their conclusions and believe that it is of interest to present our view for a balanced and comprehensive coverage of this important matter. Inprinciple,weagreewithHuangandFojothatourstudysuffers from the important limitation of a retrospective analysis; thus our investigation should be considered as hypothesis generating and certainly does not provide conclusive evidence. This problem has been clearly acknowledged in the paper, and we cautiously concluded that our study should renew interest in adjuvant therapy, whereas prospective, randomized trials will be needed to confirm the efficacyof adjuvantmitotane treatment (2).However, the rarity of ACC precluded organization of a randomized trial either in an adjuvantsettingor inpatientswithadvancedACC(3).Nonetheless, mitotane has been used for treating patients with ACC since the 1960s and is the only drug approved for ACC by the U.S. Food and Drug Administration and the European Medicines Evaluation Agency (4). In this scenario, a study including all consecutive patients treated postoperatively with mitotane in some centers and all consecutive patients left untreated after operation in other centers is thebestway toobtainexplorativedataon theefficacyofadjuvant mitotane, provided that the two groups are comparable. In our study, in fact, mitotane was recommended on the basis of the treatmentpolicyof thecenter, independentof thecharacteristicsofeither the tumorsor thepatients, and this is amajoradvantageminimizing selection bias as compared with other studies that had less clear treatment assignments (5). The major criticism of Huang and Fojo (1) is that we did not demonstrate any benefit on overall survival (OS) for patients treated adjuvantly. However, this is not correct because the hazard ratio of death of the German cohort of nontreated patients was nonsignificantly higher than mitotane-treated patients in univariate analysis, but the difference became significant in multivariate analysis after adjusting for imbalances in prognostic factors (the German cohort included more patients with stage I and II ACC than the Italian cohort of mitotane-treated patients). Even when we accept that the effect of adjuvant mitotane on OS was less impressive than on RFS, we disagree that prolonging a disease-free status is not a clinically meaningful objective even without extending significantly duration of life. In addition, there is a long-standing debate on the most appropriate endpoint for adjuvant trials, and both OS and RFS have been suggested. Analysis of RFS has the advantage of needing a shorter follow-up and being directly related to the treatment tested. The most important disadvantage of RFS is its close relationship to the frequency and quality of evaluation. Bias in follow-up or ascertainment of outcome in observational retrospective series is well recognized, and we have acknowledged this potential limit of our study. However, the follow-up procedures were highly comparable among the different centers and included imaging evaluation of the chest and abdomen every 6 months until disease progression or the end of the study period (2). Even if survival has to be considered as the reference end-point, it may not be a direct result of the study drug because it may be strongly influenced by subsequent treatments and oncologists are increasingly considering RFS as a valid surrogate for OS (6). However, this relationship has never been demonstrated specifically in ACC patients. Another criticism is derived from an ill-conceived reanalysis of our data. Huang and Fojo (1) aimed at demonstrating that the time interval between ACC recurrence and death is higher in patients treated adjuvantly than patients left untreated after surgery. Thus, they assumed important differences in tumor biology of the different cohorts. This conclusion comes from subtracting median time to recurrence from median survival observed in th
Characteristic studies on the biochars produced by hydro-thermal and steam gasification of canola hull and canola meal fuel pellets
Biochars, based on their production process and biomass precursor, can have a broad range of structural, compositional, chemical, and physical properties. These properties are important for identifying the biochar performance and stability in further applications. Non-food biomass has a great potential to produce biochars. Two inherent agricultural biomasses from Canadian prairies including canola hull and canola meal were used for the production of fuel pellets. This study provides information on the specific features of biochars produced by steam and hydro-thermal gasification of these fuel pellets compared with those of well-known pyrolysis biochars. For steam gasification, the steam to biomass ratio (SBR=0.31, 0.47, and 0.62) and gasification temperature (T=650, 750 and 850 oC) were used as the main process parameters. In contrast, for hydro-thermal (supercritical water) gasification, the effects of gasification temperature (T= 350, 450, 550, and 650 oC) were studied on the biochar properties at a constant pressure, feed concentration and reaction time. Different characterization techniques were used to study the physical, chemical, and structural characteristics of biochar products.
Characterization results, for steam-gasified biochars confirmed development of aromatic carbon structure and formation of composite char. XRD spectra for biochars produced through steam gasification showed no retention of biochemical features from the parent precursors in the biochars prepared in different levels of operating conditions. FTIR spectra confirmed the rearrangement of biomass structure at the early stages of steam gasification for all used operating conditions. Elemental analysis and Van Krevelen plot showed that for pellets, the H/C and O/C atomic ratios were in the range of biomass material. However, after gasification, the these atomic ratios for biochars were in the range of them for coal material, especially lignite coal. SEM analysis showed that steam-gasified biochars had much more cracked surface as compared with hydro-thermally prepared biochars. This observation was consistent with the results of porous characteristics for biochars which showed low BET surface area (\u3c11 \u3em2/g) for hydro-thermally produced biochars but it was much larger (\u3e 400 m2/g) for steam-gasified biochars. XRD results for hydro-thermally prepared biochars at 350 oC showed the presence of cellulose I and cellulose II in the material structure, but the related peaks were not observed for the biochar prepared at hydro-thermal gasification temperature of 650 oC. For prepared biochars prepared at the highest temperature of hydro-thermal gasification, Raman analysis showed a large change in ID/IG ratio compared with that for biochar prepared at temperature of 350 oC confirming a drastic structural change in biochar structure. Results from other characterization techniques such as XRD, ICP-MS, and thermogravimetric analysis will be also discussed in the presentation.
The degradation of biochars was progressive with the rise in hydro-thermal gasification temperature from 350 to 650°C. Hydro-thermally produced biochars showed characteristics of transition char at low temperature (350 oC as gasification temperature) and properties of amorphous char at high temperature (≥550 oC). For steam-gasified biochars, higher BET surface area indicated the development of composite char. It is noteworthy that characterization results showed that the steam-gasified biochars did not have the compact aromatic structure of turbostratic char and their aromatic structure is not developed as biochars produced via pyrolysis. However, properties of steam-gasified biochars showed their great potential for industrial applications such as adsorptive and/or catalytic applications. In addition, both types of biochars due to their mineral contents can be tested for agricultural applications(soil amendment and productivity)
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