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Pharmacodynamic Model-Based Safety Management of Eribulin-Induced Myelosuppression in Patients With Breast Cancer
No full textBACKGROUND: Neutropenia is a major dose-limiting toxicity of cancer chemotherapy. Semimechanistic mathematical models have been applied to describe the time course of neutrophil counts. The objectives of this study were to develop a mathematical model describing changes in neutrophil counts during eribulin treatment, to apply the empirical Bayes method to predict the probability of developing neutropenia ≥ grade 3 during eribulin treatment in each patient, and to propose the implementation of this mathematical tool in clinical practice for individual safety management. METHODS: The present model analysis and subsequent external evaluation were performed using the data of 481 patients with breast cancer, previously obtained from a postmarketing surveillance (training set) and a phase 2 clinical study (validation set). The model we previously reported (Kawamura et al 2018) was modified to improve its predictive capability. The individual time course of neutrophil changes during the treatment period was predicted by the empirical Bayes method using the observed neutrophil counts at baseline and the first measurement after the first eribulin dose. To evaluate the predictability of this method, the predicted neutrophil counts were compared with those of the observed values. RESULTS: The developed model provided good individual predictions, as indicated by the goodness-of-fit plots between the predicted and observed neutrophil counts, especially for a lower neutrophil count range. Days required to reach the nadir after the dose were also well-predicted. The sensitivity, specificity, and accuracy of the prediction of neutropenia grade ≥3 were 76%, 53%, and 71%, respectively. CONCLUSIONS: We developed a mathematical method for predicting and managing the risk of neutropenia during eribulin treatment. This method is generally applicable to other cases of chemotherapy-induced neutropenia and can be a new practical tool for individual safety management
Upgrading Cellulose Networks: Conquering Limitations in Fiber Foams
Get PDFThe battle to create structural materials with low environmental impact demands the investiture of two champions: porous structures and cellulose substrates. The dominant solutions when constructing strong lightweight materials are plastic and metallic foams, while currently, cellulose fiber foams suffer from challenges which hamper their development. Cellulose foams are structurally promising, but are sensitive to humidity and fire, and often have an inferior mechanical performance compared to their plastic and metallic counterparts. In addition, standard foaming techniques for cellulose fiber foams use synthetic sodium dodecyl sulfate (SDS), a surfactant which weakens critical fiber-to-fiber contacts. In this work, two approaches were employed as solutions to strengthen cellulose foams: cross-linking of cellulose fibers, and controlling pore structure formation. Phytic acid (PA), a bio-based polyphosphate, was cross-linked to cellulose fibers with the goal of improving fiber-fiber bonding and generating flame-retardancy in SDS-based cellulose foams. Controlling pore structure formation was separately achieved by dispersing tert-butanol (TBA), a water miscible amphiphile, into cellulose-water suspensions. Addition of TBA induced the formation of hierarchical structures which vastly increased the surface area and mechanical performance of dried foams. The functionalities produced by the two presented solutions expand the potential applications for cellulose foams, and serve to encourage the development of these materials as lightweight competitors in the transportation, construction and packaging sectors
A burst storm from the repeating FRB 20200120E in an M81 globular cluster
No full textThe repeating fast radio burst (FRB) source FRB 20200120E is exceptional because of its proximity and association with a globular cluster. Here we report 60 bursts detected with the Effelsberg telescope at 1.4 GHz. We observe large variations in the burst rate, and report the first FRB 20200120E \u27burst storm\u27, where the source suddenly became active and 53 bursts (fluence ≥0.04 Jy ms) occurred within only 40 min. We find no strict periodicity in the burst arrival times, nor any evidence for periodicity in the source\u27s activity between observations. The burst storm shows a steep energy distribution (power-law index α = 2.39 \ub1 0.12) and a bimodal wait-time distribution, with log-normal means of 0.94+0.07−0.06 s and 23.61+3.06−2.71 s. We attribute these wait-time distribution peaks to a characteristic event time-scale and pseudo-Poisson burst rate, respectively. The secondary wait-time peak at ∼1 s is ∼50
7 longer than the ∼24 ms time-scale seen for both FRB 20121102A and FRB 20201124A - potentially indicating a larger emission region, or slower burst propagation. FRB 20200120E shows order-of-magnitude lower burst durations and luminosities compared with FRB 20121102A and FRB 20201124A. Lastly, in contrast to FRB 20121102A, which has observed dispersion measure (DM) variations of ΔDM > 1 pc cm−3 on month-to-year time-scales, we determine that FRB 20200120E\u27s DM has remained stable (ΔDM < 0.15 pc cm−3) over >10 months. Overall, the observational characteristics of FRB 20200120E deviate quantitatively from other active repeaters, but it is unclear whether it is qualitatively a different type of source
Automated Loading and Unloading Operations: A Systematic Review
No full textPurposeMaterial handling has witnessed changes with automations occurring in the transport sector.The increasing implementation of autonomous trucks lays questions on the loading andunloading operations that the conventional truck driver used to perform. Loading and unloadingoperations interface warehouses and transportation. Conventionally characterised by themanual operating nature causing inefficiencies and discontinuities, automated loading andunloading (ALUL) benefit by enhancing workflows, improves performance, and reduceslosses. Despite these benefits, research on ALUL is minimal. This article i) details focus ofALUL systems in research, ii) indicates adopted evaluation indicators and iii) highlights keyenablers and impediments witnessed during implementation.MethodologyDevelopments are assessed by carrying out a systematic literature review including publishedliterature, technical articles etc. Review is initiated by identifying appropriate keywords,coupled with Boolean operators, to retrieve literature from scientific databases.FindingsResearch on LUL reveal a classified research focus on perception systems, manipulators, andgeneral solution type. Operating time was identified to be a commonly evaluated performanceparameter despite research revealing diverse parameters. The review highlights i) variableloading and unloading methods with changing good types. ii) Complexities in identifying andmanipulating goods. iii) Frequent human involvement, and iv) high implementation costs andassociated infrastructural modifications to influence implementation despite many enablerssupporting the implementation of this technology. Despite the above issues, commercialsolutions with varied degrees of automation are available and are listed in this article.Practical implicationsALUL systems are described comprehensively providing a detailed representation of existingknowledge regarding ALUL, making selection easier for interested industries and guiding themthrough the transformation process.OriginalityResearch aids in determining function-specific systems enabling a detailed understanding ofALUL systems
Surgical treatments for postamputation pain: study protocol for an international, double-blind, randomised controlled trial
Get PDFBACKGROUND: Painful conditions such as residual limb pain (RLP) and phantom limb pain (PLP) can manifest after amputation. The mechanisms underlying such postamputation pains are diverse and should be addressed accordingly. Different surgical treatment methods have shown potential for alleviating RLP due to neuroma formation\ua0-\ua0commonly known as neuroma pain\ua0-\ua0and to a lesser degree PLP. Two reconstructive surgical interventions, namely targeted muscle reinnervation (TMR) and regenerative peripheral nerve interface (RPNI), are gaining popularity in postamputation pain treatment with promising results. However, these two methods have not been directly compared in a randomised controlled trial (RCT). Here, we present a study protocol for an international, double-blind, RCT to assess the effectiveness of TMR, RPNI, and a non-reconstructive procedure called neuroma transposition (active control) in alleviating RLP, neuroma pain, and PLP. METHODS: One hundred ten upper and lower limb amputees suffering from RLP will be recruited and assigned randomly to one of the surgical interventions (TMR, RPNI, or neuroma transposition) in an equal allocation ratio. Complete evaluations will be performed during a baseline period prior to the surgical intervention, and follow-ups will be conducted in short term (1, 3, 6, and 12\ua0months post-surgery) and in long term (2 and 4\ua0years post-surgery). After the 12-month follow-up, the study will be unblinded for the evaluator and the participants. If the participant is unsatisfied with the outcome of the treatment at that time, further treatment including one of the other procedures will be discussed in consultation with the clinical investigator at that site. DISCUSSION: A double-blind RCT is necessary for the establishment of evidence-based procedures, hence the motivation for this work. In addition, studies on pain are challenging due to the subjectivity of the experience and the lack of objective evaluation methods. Here, we mitigate this problem by including different pain evaluation methods known to have clinical relevance. We plan to analyse the primary variable, mean change in NRS (0-10) between baseline and the 12-month follow-up, using the intention-to-treat (ITT) approach to minimise bias and keep the advantage of randomisation. The secondary outcomes will be analysed on both ITT and per-protocol (PP). An adherence protocol (PP population) analysis will be used for estimating a more realistic effect of treatment. TRIAL REGISTRATION: ClincialTrials.gov NCT05009394
Response to "Letter to the Editor Concerning \u27Simultaneous, Single-Particle Measurements of Size and Loading Give Insights into the Structure of Drug-Delivery Nanoparticles\u27"
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Sensory Design in the Birth Environment: Learning from Existing Case Studies
Get PDFStudies have shown how built environments for hospitals can influence psychological and physiological conditions and status for childbearing women. Sensory attributes of birth spaces can enhance comfort, feelings of wellbeing, and, to some extent, clinical outcomes. Recently, some case studies of multisensory rooms for the birth environment have been developed based on, e.g., Snoezelen room examples. The aim of this research is to develop an overview of how sensory aspects for birth environments are designed, used, and tested in current and recent studies. Case studies were selected according to sensory aspect significance, observing space factors, and relationship with the experience and comfort of users (women, partners, midwives). All case studies were analysed to collect information about the design and validation process. The collected data were organised in categories and compared for the selected case studies. Main findings were summarised in tables with the aim of underlining how sensory design processes and projects can positively influence comfort for birthing. Conclusions about how to bring forward the issue of sensory design so that it can be used and applied to support childbearing women is discussed
Efficient low-loaded ternary Pd-In2O3-Al2O3 catalysts for methanol production
Get PDFPd-In2O3 catalysts are among the most promising alternatives to Cu-ZnO-Al2O3 for synthesis of CH3OH from CO2. However, the intrinsic activity and stability of In2O3 per unit mass should be increased to reduce the content of this scarcely available element and to enhance the catalyst lifetime. Herein, we propose and demonstrate a strategy for obtaining highly dispersed Pd and In2O3 nanoparticles onto an Al2O3 matrix by a one-step coprecipitation followed by calcination and activation. The activity of this catalyst is comparable with that of a Pd-In2O3 catalyst (0.52 vs 0.55 gMeOH h−1 gcat-1 at 300 \ub0C, 30 bar, 40,800 mL h−1 gcat-1) but the In2O3 loading decreases from 98 to 12 wt% while improving the long-term stability by threefold at 30 bar. In the new Pd-In2O3-Al2O3 system, the intrinsic activity of In2O3 is highly increased both in terms of STY normalized to In specific surface area and In2O3 mass (4.32 vs 0.56 g gMeOH h−1 gIn2O3-1 of a Pd- In2O3 catalyst operating at 300 \ub0C, 30 bar, 40,800 mL h−1 gcat-1).The combination of ex situ and in situ catalyst characterizations during reduction provides insights into the interaction between Pd and In and with the support. The enhanced activity is likely related to the close proximity of Pd and In2O3, wherein the H2 splitting activity of Pd promotes, in combination with CO2 activation over highly dispersed In2O3 particles, facile formation of CH3OH