Combined Scheduling Research Articles

Solution of short term integrated hydrothermal-solar-wind scheduling using sine cosine algorithm

The combined scheduling of hydro, thermal and hybrid energy (i.e., wind and solar) is attracting more and more attention nowadays. This paper explores the contribution of renewable energy sources in the traditional hydrothermal scheduling problem in order to overcome the prevailing issues like high generation cost and more emissive particles of fuel. This paper presents a new wind-solar based generation scheduling model that reduces the aforementioned issues. The proposed hydrothermal-solar-wind scheduling (HTSWS) model is very effective. It can reduce the price rate of generation and different emissive particles of fuel of the traditional scheduling model. A solution approach i.e., robust sine cosine algorithm (SCA) is employed to determine the minimum generation cost and fuel emission based best generating schedule for traditional scheduling problem. The same approach has been carried out in the context of the suggested HTSWS problems. The different control parameters of the SCA have been properly utilized to balance the exploration and the exploitation phases. These parameters lead to determination of the near-optimal global solution. The results show that the combined application of renewable sources and hydrothermal units benefit both economic and emission goals of the utility houses with operating costs and pollutant emissions falling by 10% and 64%, respectively. Here, another two powerful algorithms (i.e., backtracking search algorithm and whale algorithm) have also been applied to determine the minimum values of generation cost, emission, and combined generation cost-emission. Effectiveness and robustness of the proposed algorithm have been presented by comparing the SCA based results with other established latest algorithms for the considered problems.

Abstract P2-14-15: Timing of the immunization defines immune signature of a peptide cancer vaccine combined with Neoadjuvant chemotherapy in HR+ breast cancer patients

Abstract Background: We have developed P10s-PADRE, a carbohydrate-mimetic-based peptide, cancer vaccine and demonstrated its safety and immunogenicity in a Phase I clinical trial performed in stage IV breast cancer patients. HR+/HER2- breast cancer is the most common form of breast cancer diagnosed in the United States. These patients face a persistent risk of distant recurrence long after completion of their treatment and new strategies to activate anti-tumor immune responses can improve outcomes of standard therapies. The current study was performed to examine the feasibility, safety and immunogenicity of adding P10s-PADRE to standard-of-care chemotherapy in HR+/HER2− early-stage breast cancer patients. Methods: Five combination schedules were designed based on the timing of immunizations relative to a standard-of-care neoadjuvant chemotherapy regimen. Induction of on-treatment antibody and cellular responses, including T-cells, natural killer (NK) cells, and cytokines was determined. Tumor-infiltrating lymphocytes were quantified in core and surgical biopsies. The data were used to define the treatment effect in general and the vaccine contribution in particular. Results: Combination of P10s-PADRE with chemotherapy was safe and immunogenic. Antibody response was superior in a particular combination schedule, called schedule C, where 3 weekly immunizations preceded the first dose of chemotherapy. We observed that the schedule C, relative to other schedules, displayed an increase in CD16 expression on NK cells, a drop in serum IFN-γ, and an increase in quantity of stromal TILs in residual tumors. Subjects demonstrated a significant reduction in the size of their primary tumor and three subjects achieved pCR. Conclusions: The timing of the immunization relative to the chemotherapy seems to define the type and strength of the immune responses elicited. A particular combination schedule, schedule C, appears promising and the results warrant the conduct of randomized phase II trials. Citation Format: Issam Makhoul, Saddam M Ibrahim, Muhammad Abu-Rmaileh, Fariba Jousheghany, Eric Siegel, Lora J Rogers, John J Lee, Sergio Pina-Oviedo, Ginell R Post, Thaddeus Beck, Thomas Kieber-Emmons, Behjatolah Monzavi-Karbassi. Timing of the immunization defines immune signature of a peptide cancer vaccine combined with Neoadjuvant chemotherapy in HR+ breast cancer patients [abstract]. In: Proceedings of the 2021 San Antonio Breast Cancer Symposium; 2021 Dec 7-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2022;82(4 Suppl):Abstract nr P2-14-15.

Avacopan, a selective C5a receptor antagonist, for anti-neutrophil cytoplasmic antibody-associated vasculitis.

Avacopan, an orally administered C5a receptor antagonist, has been approved for the treatment of microscopic polyangiitis (MPA) and granulomatosis with polyangiitis (GPA) in Japan and the USA. In ADVOCATE Phase III clinical trial, patients with active MPA or GPA received either 30 mg avacopan twice daily or prednisone on a tapering schedule in combination with rituximab or cyclophosphamide (followed by azathioprine). The trial met its two primary endpoints: avacopan showed non-inferiority to prednisone for achieving remission at Week 26 (avacopan, 72.3%; prednisone, 70.1%; p < .001 for non-inferiority and p = .24 for superiority) and superiority for maintaining remission at Week 52 (65.7% for avacopan, 54.9% prednisone, p < .001 for non-inferiority and p = .007 for superiority). Of several key secondary endpoints tested, the glucocorticoid toxicity index (GTI)-cumulative worsening score and GTI-aggregate improvement score were significantly lower in the avacopan group than in the prednisone group at both Weeks 26 and 52. Serious adverse events related and unrelated to the worsening vasculitis were reported at 10.2% and 37.3% in the avacopan group and at 14.0% and 39.0% in the prednisone group, respectively. Avacopan has set the stage for the semi-glucocorticoid-free or glucocorticoid-free treatment of MPA and GPA.

Evolutionary analysis of replicator dynamics about anti-cancer combination therapy.

The emergence and growth of drug-resistant cancer cell subpopulations during anti-cancer treatment is a major challenge for cancer therapies. Combination therapies are usually applied for overcoming drug resistance. In the present paper, we explored the evolution outcome of tumor cell populations under different combination schedules of chemotherapy and p53 vaccine, by construction of replicator dynamical model for sensitive cells, chemotherapy-resistant cells and p53 vaccine-resistant cells. The local asymptotic stability analysis of the evolutionary stable points revealed that cancer population could evolve to the population with single subpopulation, or coexistence of sensitive cells and p53 vaccine-resistant cells, or coexistence of chemotherapy-resistant cells and p53 vaccine-resistant cells under different monotherapy or combination schedules. The design of adaptive therapy schedules that maintain the subpopulations under control is also demonstrated by sequential and periodic application of combination treatment strategies based on the evolutionary velocity and evolutionary absorbing regions. Applying a new replicator dynamical model, we further explored the supportive effects of sensitive cancer cells on targeted therapy-resistant cells revealed in mice experiments. It was shown that the supportive effects of sensitive cells could drive the evolution of cell population from sensitive cells to coexistence of sensitive cells and one type of targeted therapy-resistant cells.

Resilience Optimization of Wide-Area Control in Smart Distribution Grids

Large-scale power distribution networks rely on the wide-area control (WAC) function to conduct daily grid operations. Grid control is even more critical during extreme events as the WAC function is required to orchestrate the response to contingencies and enhance the power system resilience through failure localization, isolation, and service restoration. Both power and telecommunication domains are involved in control applications, giving rise to multiple cyber-physical interdependencies. This paper proposes a resilience-based optimization of the distribution service restoration (DSR) by coordinating strategies of crew dispatch and manual/remote switches operation. The telecommunication service and underlying infrastructure are identified as main enablers of the co-optimization as all considered resilience strategies communicate with the control center that collects crisis management information. Therefore, the availability of telecom points in terms of power supply is examined in this work. Failure propagation in the coupled power-telecom network is highlighted, and differences in failure propagation between overhead and underground power lines are explored. The proposed approach is formulated as a mixed-integer linear programming (MILP) model, evaluated under a multi-feeder interdependent power-telecom test network. Results show that combined scheduling of resilience strategies as well as prioritization of power supply to telecom points-of-interest, yield an enhanced recovery strategy.

Vaccine effectiveness against SARS-CoV-2 infection, hospitalization, and death when combining a first dose ChAdOx1 vaccine with a subsequent mRNA vaccine in Denmark: A nationwide population-based cohort study.

The recommendations in several countries to stop using the ChAdOx1 vaccine has led to vaccine programs combining different Coronavirus Disease 2019 (COVID-19) vaccine types, which necessitates knowledge on vaccine effectiveness (VE) of heterologous vaccine schedules. The aim of this Danish nationwide population-based cohort study was therefore to estimate the VE against Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) infection and COVID-19-related hospitalization and death following the first dose of the ChAdOx1 vaccine and the combination of the ChAdOx1/mRNA vaccines. All individuals alive in or immigrating to Denmark from 9 February 2021 to 23 June 2021 were identified in the Danish Civil Registration System. Information on exposure, outcomes, and covariates was obtained from Danish national registries. Poisson and Cox regression models were used to calculate crude and adjusted VE, respectively, along with 95% confidence intervals (CIs) against SARS-CoV-2 infection and COVID-19-related hospitalization or death comparing vaccinated versus unvaccinated individuals. The VE estimates were adjusted for calendar time as underlying time and for sex, age, comorbidity, country of origin, and hospital admission. The analyses included 5,542,079 individuals (97.6% of the total Danish population). A total of 144,360 individuals were vaccinated with the ChAdOx1 vaccine as the first dose, and of these, 136,551 individuals received an mRNA vaccine as the second dose. A total of 1,691,464 person-years and 83,034 SARS-CoV-2 infections were included. The individuals vaccinated with the first dose of the ChAdOx1 vaccine dose had a median age of 45 years. The study population was characterized by an equal distribution of males and females; 6.7% and 9.2% originated from high-income and other countries, respectively. The VE against SARS-CoV-2 infection when combining the ChAdOx1 and an mRNA vaccine was 88% (95% CI: 83; 92) 14 days after the second dose and onwards. There were no COVID-19-related hospitalizations or deaths among the individuals vaccinated with the combined vaccine schedule during the study period. Study limitations including unmeasured confounders such as risk behavior and increasing overall vaccine coverage in the general population creating herd immunity are important to take into consideration when interpreting the results. In this study, we observed a large reduction in the risk of SARS-CoV-2 infection when combining the ChAdOx1 and an mRNA vaccine, compared with unvaccinated individuals.

Description of multimodal transport networks by means of graph models

The main objective of organising multimodal transport is to meet the public’s demand for transport services as much as possible while making the most efficient use of rolling stock. In order to determine the efficiency of a transport system the paper proposes that it should be viewed as a collection of different local transport systems. The issue of organising multimodal transport is related to many aspects of passenger services and rail transport operations (forecasting passenger flows, developing combined train schedules, features of the TH (transfer hub) and station complexes, etc.). The article details the way multimodal passenger chains are represented in the form of graphical models. The goals of using the constructed graphs are defined: solving problems of visualisation and analysis of multimodal transport chains as well as solving the complex problem of optimising the scheduling and planning of vehicle stops at passenger transfer points. It has been shown that the main requirements for organising this type of passenger transport are to minimise the total travel time of vehicles in order to reduce management costs for operators and to maximise the number of passengers carried in order to better meet passenger demand.

Pneumococcal Immunization Strategies for High-Risk Pediatric Populations Worldwide: One Size Does Not Fit All.

Despite the significant reduction in pneumococcal disease due to pneumococcal vaccines, protection of vulnerable high-risk individuals, especially pediatric populations, remains a great challenge. In an effort to maximize the protection of high-risk children against pneumococcal disease, a combined schedule that includes both conjugate and polysaccharide vaccines is recommended by several countries in the developed world. On the other hand, middle- and low-income countries do not have in place established policies for pneumococcal immunization of children at risk. Pneumococcal conjugate vaccines, despite their benefits, have several limitations, mainly associated with serotype replacement and the wide range of serotype coverage worldwide. In addition, PPV23-impaired immunogenicity and the hyporesponsiveness effect among populations at risk have been well-documented. Therefore, the added value of continuing to include PPV23 in vaccination schedules for high-risk individuals in the years to come remains to be determined by monitoring whether the replacing/remaining serotypes causing IPD are covered by PPV23 to determine whether its benefits outweigh its limitations. In this review, we aim to describe serotype distribution and vaccine efficacy data on pneumococcal disease in the pre- and post-PCV implementation era among high-risk children in both developed and developing countries, assessing the optimization of current recommendations for their vaccination against pneumococcal disease.

FMixFN: A Fast Big Data-Oriented Genomic Selection Model Based on an Iterative Conditional Expectation algorithm.

Genomic selection is an approach to select elite breeding stock based on the use of dense genetic markers and that has led to the development of various models to derive a predictive equation. However, the current genomic selection software faces several issues such as low prediction accuracy, low computational efficiency, or an inability to handle large-scale sample data. We report the development of a genomic prediction model named FMixFN with four zero-mean normal distributions as the prior distributions to optimize the predictive ability and computing efficiency. The variance of the prior distributions in our model is precisely determined based on an F2 population, and genomic estimated breeding values (GEBV) can be obtained accurately and quickly in combination with an iterative conditional expectation algorithm. We demonstrated that FMixFN improves computational efficiency and predictive ability compared to other methods, such as GBLUP, SSgblup, MIX, BayesR, BayesA, and BayesB. Most importantly, FMixFN may handle large-scale sample data, and thus should be able to meet the needs of large breeding companies or combined breeding schedules. Our study developed a Bayes genomic selection model called FMixFN, which combines stable predictive ability and high computational efficiency, and is a big data-oriented genomic selection model that has potential in the future. The FMixFN method can be freely accessed at https://zenodo.org/record/5560913 (DOI: 10.5281/zenodo.5560913).

Use of Azacitidine or Decitabine for the Up-Front Setting in Acute Myeloid Leukaemia: A Systematic Review and Meta-Analysis.

Simple SummaryAzacitidine and decitabine have been increasingly used for the treatment of acute myeloid leukaemia in older patients. The choice between azacitidine and decitabine depends mostly on the experience and preference of the attending physician, since they have not been compared directly in a randomised clinical trial. In this study, we identified the best treatment regimen for each drug and compare the efficacy of decitabine and azacitidine monotherapy in newly diagnosed acute myeloid leukaemia. We found no significant differences regarding 1-year mortality and overall survival for azacitidine and decitabine (roughly 9 months). Moreover, there were no significant differences in the efficacy of 5-day versus 10-day schedules of decitabine. However, patients treated with the shortened 5-day azacitidine scheme showed worsened outcomes compared to the standard 7-day regimen. Hopefully, our results might be helpful for the design of azacitidine/decitabine-based combination schedules to be tested in future trials.Irruption of decitabine and azacitidine has led to profound changes in the upfront management of older acute myeloid leukaemia (AML). However, they have not been directly compared in a randomised clinical trial. In addition, there are no studies comparing the optimal treatment schedule of each drug in AML. A systematic review and meta-analysis on the efficacy of decitabine and azacitidine monotherapy in newly diagnosed AML was conducted. Randomised controlled trials and retrospective studies were included. A total of 2743 patients from 23 cohorts were analysed (10 cohorts of azacitidine and 13 of decitabine). Similar response rates were observed for azacitidine (38%, 95% CI: 30–47%) compared to decitabine (40%, 95% CI: 32–48%) (p = 0.825). Overall survival (OS) between azacitidine (10.04 months, 95% CI: 8.36–11.72) and decitabine (8.79 months, 95% CI: 7.62–9.96) was also similar (p = 0.386). Patients treated with azacitidine showed a lower median OS when azacitidine was administered for 5 days (6.28 months, 95% CI: 4.23–8.32) compared to the standard 7-day schedule (10.83 months, 95% CI: 9.07–12.59, p = 0.002). Among patients treated with decitabine, response rates and OS were not significantly different between 5-day and 10-day decitabine regimens. Despite heterogeneity between studies, we found no differences in response rates and OS in AML patients treated with azacitidine or decitabine.

High-Dose Carfilzomib Recaptures Response in Relapsed/Refractory Multiple Myeloma Resistant to Low-Dose Carfilzomib By Co-Inhibiting β2 Subunit of Proteasome Complex: The First in Human Evidence

BackgroundProteasome, a complex involved in the intracellular protein degradation, consists of multiple subunits, but only three subunits have enzymatic activity to cleave and degrade proteins, namely β1, β2 and β5. Carfilzomib (CFZ), a second-generation proteasome inhibitor (PI), can induce cell death by selective and irreversible inhibition of β5 subunit of proteasome. Preclinical data suggested that high-dose CFZ could co-inhibit predominantly β2 proteasome activity, followed by β1 inhibition (Besse et al, Cell Chem Biol. 2019). Over the past few years, CFZ has become a corner stone for multiple myeloma (MM) therapy. Currently, CFZ is approved by the FDA in different dosing schedules in combination with lenalidomide or daratumumab and dexamethasone. However, the optimal CFZ dosing is still a matter of debate, with the approved dosage ranging from 20to 70mg/m 2 in different regimens. In addition, if response can be recaptured by escalating CFZ dose in patients progressing from low-dose CFZ has yet to be determined. The aim of our current study was to analyse the profile of proteasome inhibition in the respective dose cohorts and to elucidate if high-dose CFZ could recapture response in patients resistant to low-dose CFZ.MethodsWe prospectively collected clinical data and peripheral blood mononuclear cells (PBMC) of 32 patients with relapsed/refractory (RR) MM before and 1-8 hours after CFZ administration. PBMC were lysed and labelled for the activity of individual proteasome subunits using activity based proteasome probes and the proteasome subunits were separated using SDS-PAGE. The activity of constitutive and immunoproteasome β1, β2 and β5 subunits was evaluated by densitometry analysis and combination of the activity of constitutive and immunoproteasome individual subunit was used for further analysis.ResultsOverall, six, nine, twelve and five patients received CFZ at a dose of 20, 27, 36 and 56 mg/m 2, respectively. As expected, the total activity of proteasome decreased with higher doses of CFZ. Significant inhibition (median inhibition > 50%) of β5 subunit was observed already at 20 mg/m 2 dose, while β2 subunit started to be co-inhibited only at a dose of ≥27 mg/m 2. Significant co-inhibition of β2 activity was seen at 36 mg/m 2 dose, at which also β1 subunit started to be co-inhibited. Finally, at 56 mg/m 2, the activity of all active subunits was inhibited with a median inhibition of > 50%, with the strongest inhibition of the β5 subunit, followed by β2 and then β1. When we compared the patient groups low-dose CFZ (20 or 27 mg/m 2) versus high-dose CFZ (36 or 56 mg/m 2), we observed a significant difference in β2 (P=0.002) and β5 (P=0.02) subunit inhibition between the both groups. In terms of total proteasome activity, high-dose CFZ demonstrated a significantly higher proteasome inhibition in comparison with patients receiving low-dose CFZ (P=0.01). In brief, our results suggested that high-dose CFZ, in contrast to low-dose CFZ, could obtain superior proteasome inhibition by co-inhibiting β2 subunit of proteasome complex.In light of this finding, we successfully treated six RRMM patients who were resistant to low-dose CFZ with CFZ dose escalation. All six patients were heavily pretreated with 3-12 lines of therapy including daratumumab, two PIs, two immunomodulatory drugs and autologous stem cell transplant. Additionally, one and two patients received prior treatment with B-cell maturation antigen targeted bi-specific antibody and chimeric antigen receptor modified T-cell, respectively. In the last line of treatment, these six patients showed progression during CFZ based regimens with low-dose CFZ, namely 20 or 27 mg/m 2. We therefore increased the CFZ dose to 36 or 56 mg/m 2 and the doses of agents other than CFZ in the combination regimens remained the same. High-dose CFZ dose recaptured response in all six patients with four and two patients that achieved partial remission and very good partial remission, respectively, and the progression free survival ranged from 1-13 months.ConclusionIn summary, high-dose CFZ, namely ≥ 36mg/m 2, showed more effective proteasome inhibition via blocking β5 and β2 subunits, while low-dose CFZ could not achieve a sufficient inhibition of β2 subunit. We provided the first in human evidence that high-dose CFZ could recapture response in RRMM patients resistant to low-dose CFZ by co-inhibiting the β2 subunit activity of proteasome complex. [Display omitted] DisclosuresEinsele: Janssen, Celgene/BMS, Amgen, GSK, Sanofi: Consultancy, Honoraria, Research Funding.

Simultaneous scheduling of machines and tools in a multi machine FMS with alternative routing using symbiotic organisms search algorithm

This paper deals with simultaneous scheduling of machines and tools with alternate machines in a multi machine flexible manufacturing system (FMS) to minimize makespan (MS). Only one copy of each type of tools is made available due to economic restrictions and the tools are stored in a central tool magazine (CTM) that shares with and serves for several machines. The problem is to select machines from alternate machines for job-operations, allocation of tools to job-operations and job-operations’ sequencing on machines for MS minimization. This paper presents a nonlinear mixed integer programming (MIP) formulation to model the combined scheduling of machines and tools with alternate machines and a symbiotic organisms search algorithm (SOSA) built on the symbiotic interaction strategies that organisms employ to continue to exist in the ecosystem for solving the scheduling of machines and tools with alternate machines. The results have been tabulated, analyzed. It is observed that there is a reduction in MS when the alternate machines are considered for job-operation.

Cost-Effectiveness of the Dabrafenib Schedule in Combination With Trametinib Compared With Other Targeted Therapies, Immunotherapy, and Dacarbazine for the Treatment of Unresectable or Metastatic Melanoma With BRAFV600 Mutation in Colombia

ObjectivesAdvanced melanoma accounts for 4% of malignant skin tumors, and approximately 80% of deaths are attributed to it. The most frequent mutation of the RAF gene is BRAFV600, which has been associated with a worse prognosis. The objective of the research was to evaluate the cost-effectiveness of the combined regimen of dabrafenib plus trametinib (D + T) compared with other targeted therapies, immunotherapy, and dacarbazine for the treatment of unresectable/metastatic melanoma with BRAFV600 mutation from the perspective of the Colombian health system. MethodsA partitioned survival model with 3 states (progression-free survival, progression, and death) was used to evaluate the cost-effectiveness for a time horizon of 20 years. Owing to the perspective of the analysis, only direct medical costs were taken into account. The efficacy of the evaluated treatment and the comparators were measured in terms of overall survival and progression-free survival. All costs were expressed in Colombian pesos as of 2018, and outcomes and costs were discounted at 5% annually. Two analysis scenarios were considered, one in which only monitoring and follow-up costs were included in the progression phase and another in which costs of acquisition of possible treatment sequences were also included. ResultsIn the first scenario (without postprogression medication costs), the combined D + T regimen was a dominant alternative to vemurafenib + cobimetinib but was not a cost-effective option compared with vemurafenib, nivolumab, ipilimumab, nivolumab + ipilimumab, pembrolizumab, and dacarbazine. In the second scenario (with drug costs in postprogression), D + T was dominant compared with vemurafenib + cobimetinib and cost-effective compared with nivolumab and pembrolizumab. Compared with other schemes, the incremental cost-effectiveness ratio was above the threshold of 3 gross domestic product per capita. Probabilistic sensitivity analyses showed that a willingness-to-pay threshold of Col$56 484 300 (US$19 108) per quality-adjusted life-year would not be reached at the current price of schema in Colombia. ConclusionsThe combined scheme could be a cost-effective and even a cost-saving alternative to vemurafenib + cobimetinib, nivolumab, and pembrolizumab if the costs associated with the use of other medications are taken into account after progression to the first line of treatment. Compared with the other comparators, it produces a greater number of quality-adjusted life-years, but the incremental cost-effectiveness ratio is above that of the willingness to pay.

Renewable hydrogen and ammonia for combined heat and power systems in remote locations: Optimal design and scheduling

AbstractUsing hydrogen (H) and ammonia (NH) for renewable energy storage has the potential to enable economical power and heat supply with high renewable penetrations, especially in remote locations which are characterized by high energy costs. In this work we assess the economic competitiveness of renewable combined heat and power (CHP) systems in Mahaka HI, Nantucket MA, and Northwest Arctic Borough (NWAB) AK by optimally designing these systems for scenarios in which power and heat can be purchased over a range of historical energy prices as well as when 100% renewable supply is required. We use a combined optimal design and scheduling model which minimizes annualized net present cost by determining optimal technology selection and size simultaneously with optimal schedules for each period of a system operating horizon aggregated from full year hourly resolution data via a consecutive temporal clustering algorithm. We find that renewable generation meets at least 85% of power demands and 75% of heat demands under the lowest energy prices investigated. Higher conventional energy prices lead to increased renewable penetration which is facilitated by renewable NH as a seasonal energy storage medium, as are 100% renewable CHP systems. NH is used for power generation with heat cogeneration in all three locations, as well as directly for heating in NWAB. On an annual cost basis, NH‐enabled 100% renewable CHP is only 3% more expensive in Mahaka and NWAB than systems which can purchase energy at the lowest prices, while it is 15% more expensive in Nantucket.

800P Tailoring adjuvant treatments in high-risk early stage endometrial cancer: Clinical outcomes of sequential chemoradiation in a real-word scenario

Chemotherapy plus external beam radiotherapy (EBRT) is the current standard adjuvant therapy for patients (pts) with high-risk stage I-III endometrial cancer (EC). Despite this, the best combination schedule for chemoradiation (CR) has not been defined yet. We aimed at describing the clinical outcomes of pts with EC receiving platinum-based chemotherapy administered 2-3 cycles before and after radiotherapy as adjuvant treatment (‘sandwich’ chemoradiation, SCR).

AML-266: Azacitidine or Decitabine Monotherapy for the Treatment of AML: A Comparative Systematic Review and Meta-Analysis

<h3>Context:</h3> Decitabine and azacitidine have been increasingly used to treat patients with acute myeloid leukemia (AML) who are elderly or not suitable for intensive chemotherapy. Despite their widespread use, there is no consensus on their efficacy, with considerable variability between studies. <h3>Objective:</h3> Our aim was to analyze and compare the efficacy of azacitidine and decitabine for the treatment of AML in elderly patients and/or patients not suitable for intensive chemotherapy. <h3>Design:</h3> A systematic review and meta-analysis was conducted. <h3>Patients or Other Participants:</h3> Trials were selected if performed on patients not eligible for intensive chemotherapy. The meta-analysis only includes data from the azacitidine or decitabine monotherapy arms; data from experimental arms were excluded from the analysis. <h3>Interventions:</h3> The results were summarized using a point estimate and 95% confidence interval (CI) for the means of the different outcomes between studies. <h3>Main Outcome Measures:</h3> Studies had to report at least one of the following outcomes: mortality, overall survival (OS), complete remission, complete remission with incomplete hematological recovery, or partial response. <h3>Results:</h3> The search strategy revealed 681 citations before duplicates were removed. Finally, 20 articles were included after analysis of abstracts and full text. A total of 3,000 patients from 23 cohorts were analyzed (12 cohorts of azacitidine and 11 of decitabine). A trend toward lower response rates was observed for azacitidine (31%, 95%CI: 24%–37%) compared to decitabine (40%, 95%CI: 31%–49%o, p=0.081). However, there was no significant difference in OS between azacitidine (9.99 months, 95%CI: 8.17–11.82) and decitabine (8.88 months, 95%CI: 7.67–10.08, p=0.550). Lower 1-year mortality with standard 7-day 75 mg/m² azacytidine treatment was observed compared to other azacitidine schedules (51%, 95%CI: 46%-57% <i>vs</i> 72%, 95%CI: 61%-82%, p=0.001). Moreover, OS was lower when administered for 5 days (6.28 months, 95%CI: 4.23-8.32) <i>versus</i> 7 days (10.90 months, 95%CI: 8.92–12.89, p=0.002). However, there was no significant difference in response rates, mortality, and OS when comparing the 5-day <i>vs</i> 10-day decitabine regimens. <h3>Conclusions:</h3> There were no significant differences in 1-year mortality or OS for azacitidine and decitabine (roughly 9 months). These results exploring single-HMA regimens could be useful for the design and use of new HMA-based combination schedules.

Is the Combination of ADOS and ADI-R Necessary to Classify ASD? Rethinking the "Gold Standard" in Diagnosing ASD.

Diagnosing autism spectrum disorder (ASD) requires extensive clinical expertise and training as well as a focus on differential diagnoses. The diagnostic process is particularly complex given symptom overlap with other mental disorders and high rates of co-occurring physical and mental health concerns. The aim of this study was to conduct a data-driven selection of the most relevant diagnostic information collected from a behavior observation and an anamnestic interview in two clinical samples of children/younger adolescents and adolescents/adults with suspected ASD. Via random forests, the present study discovered patterns of symptoms in the diagnostic data of 2310 participants (46% ASD, 54% non-ASD, age range 4–72 years) using data from the combined Autism Diagnostic Observation Schedule (ADOS) and Autism Diagnostic Interview—Revised (ADI-R) and ADOS data alone. Classifiers built on reduced subsets of diagnostic features yield satisfactory sensitivity and specificity values. For adolescents/adults specificity values were lower compared to those for children/younger adolescents. The models including ADOS and ADI-R data were mainly built on ADOS items and in the adolescent/adult sample the classifier including only ADOS items performed even better than the classifier including information from both instruments. Results suggest that reduced subsets of ADOS and ADI-R items may suffice to effectively differentiate ASD from other mental disorders. The imbalance of ADOS and ADI-R items included in the models leads to the assumption that, particularly in adolescents and adults, the ADI-R may play a lesser role than current behavior observations.

Differentiation of autism spectrum disorder and mood or anxiety disorder.

Autism spectrum disorder shares many symptoms with other mental health disorders, and comorbid disorders such as mood and anxiety disorders are common, making the diagnostic process challenging. We aimed to explore the diagnostic accuracy of two standard autism spectrum disorder diagnostic instruments and to identify those behavioral items that best differentiate between autism spectrum disorder and mood and anxiety disorder in a naturalistic sample of patients utilizing autism spectrum disorder specialist services. The study included data of 847 participants (5–65 years of age, n = 586 with autism spectrum disorder, n = 261 with mood and anxiety disorder) all evaluated with the Autism Diagnostic Observation Schedule in the context of the diagnostic process. Data of the Autism Diagnostic Interview–Revised were available for 428 participants (5–51 years of age, n = 367 with autism spectrum disorder, n = 61 with mood and anxiety disorder). By means of binominal logistic regressions and an ensemble feature selection, we identified a subset of items that best differentiated between autism spectrum disorder and mood and anxiety disorder. Overall, the results indicate that a combination of communicational deficits and unusual and/or inappropriate social overtures differentiates autism spectrum disorder and mood and anxiety disorder. Aspects of social cognition are also relevant. Limitations of the current study and implications for research and practice are discussed.Lay abstractSymptoms of mood and anxiety disorders overlap with symptoms of autism spectrum disorder, making the diagnostic process challenging. This study found that a combination of communicational deficits and unusual and/or inappropriate social overtures facilitates differentiation between autism spectrum disorder and mood and anxiety disorders. Furthermore, the results confirm the essential need of a behavioral observation with the Autism Diagnostic Observation Schedule in combination with a full Autism Diagnostic Interview–Revised to support diagnostic decisions.

BatRack: An open‐source multi‐sensor device for wildlife research

Abstract Bats represent a highly diverse group of mammals and are essential for ecosystem functioning. However, knowledge about their behaviour, ecology and conservation status is limited. Direct observation of marked individuals (commonly applied to birds) is not possible for bats due to their small size, rapid movement and nocturnal lifestyle, while neither popular observation methods such as camera traps nor conventional tracking technologies sufficiently capture the behaviour of individuals. The combination and networking of different sensors in a single system can overcome these limitations, but this potential has been explored only to a limited extent. We present BatRack, a multi‐sensor device that combines ultrasonic audio recordings, automatic radio telemetry and video camera recordings in a single modular unit. BatRack facilitates the individual or combined scheduling of sensors and includes a mutual triggering mode. It consists of off‐the‐shelf hardware and both its hardware blueprints and the required software have been published under an open license to allow scientists and practitioners to replicate the system. We tested the suitability of radio telemetry and audio sensors as camera triggers and evaluated the detection of individuals in video recordings compared to radio telemetry signals. Specifically, BatRack was used to monitor the individual swarming behaviour of six members of a maternity colony of Bechstein's bat. Preliminary anecdotal results indicate that swarming intensity is related to reproductive state and roost switching. BatRack allows researchers to recognize individual bats and monitor their behavioural patterns using an easily deployed and scalable system. BatRack is thus a promising approach to obtaining detailed insights into the behavioural ecology of bats.

Combining workload balance and patient priority maximisation in operating room planning through hierarchical multi-objective optimisation

Previous analysis suggested the opportunity to consider the preferences of different stakeholders (hospital, patients, doctors and nurses) through the adoption of both patient priority maximisation and workload balance as performance criteria. The aim of this paper is to develop an effective and efficient solution approach for the operating room planning and scheduling capable to take into account the patient priority maximisation and workload balance criteria at the same time. This work is inspired by the need of a deeper understanding of the quality of the solutions obtained when a combination of the two criteria leads the OR planning decisions. Starting from a hierarchical multi-objective optimisation model for the combined master surgical scheduling and surgical cases assignment problems, we develop a class of new multi-neighbourhood local search based matheuristic algorithms, whose main feature is to exploit an ad hoc neighbourhood to generate better solutions in a significant shorter running time. A broad quantitative analysis on new realistic instances proves the effectiveness and the efficiency of the proposed matheuristic algorithms as well as to evaluate the quality of the computed solution from an operating room management perspective.