Data-Driven Predictive Control With Improved Performance Using Segmented Trajectories

A class of data-driven control methods has recently emerged based on Willems’ fundamental lemma. Such methods can ease the modeling burden in control design but can be sensitive to disturbances acting on the system under control. In this article, we propose a restructuring of the problem to incorporate segmented prediction trajectories. The proposed segmentation leads to reduced tracking error for longer prediction horizons in the presence of unmeasured disturbance and noise when compared with an unsegmented formulation. The performance characteristics are illustrated in a set-point tracking case study in which the segmented formulation enables more consistent performance over a wide range of prediction horizons. The method is then applied to a building energy management problem using a detailed simulation environment. The case studies show that good tracking performance is achieved for a range of horizon choices, whereas performance degrades with longer horizons without segmentation

Clinical and exploratory biomarker findings from the MODUL trial (Cohorts 1, 3 and 4) of biomarker-driven maintenance therapy for metastatic colorectal cancer

Biomarkers; Colorectal cancer; Maintenance therapyBiomarcadors; Càncer colorectal; Teràpia de mantenimentBiomarcadores; Cáncer colorrectal; Terapia de mantenimientoPurpose MODUL is an adaptable, signal-seeking trial of biomarker-driven maintenance therapy following first-line induction treatment in patients with metastatic colorectal cancer (mCRC). We report findings from Cohorts 1 (BRAFmut), 3 (human epidermal growth factor 2 [HER2]+) and 4 (HER2‒/high microsatellite instability, HER2‒/microsatellite stable [MSS]/BRAFwt or HER2‒/MSS/BRAFmut/RASmut). Methods Patients with unresectable, previously untreated mCRC without disease progression following standard induction treatment (5-fluorouracil/leucovorin [5-FU/LV] plus oxaliplatin plus bevacizumab) were randomly assigned to control (fluoropyrimidine plus bevacizumab) or cohort-specific experimental maintenance therapy (Cohort 1: vemurafenib plus cetuximab plus 5-FU/LV; Cohort 3: capecitabine plus trastuzumab plus pertuzumab; Cohort 4: cobimetinib plus atezolizumab). The primary efficacy end-point was progression-free survival (PFS). Results Cohorts 1, 3 and 4 did not reach target sample size because of early study closure. In Cohort 1 (n = 60), PFS did not differ between treatment arms (hazard ratio, 0.95; 95% confidence intervals 0.50–1.82; P = 0.872). However, Cohort 1 exploratory biomarker data showed preferential selection for mitogen-activated protein kinase (MAPK) pathway mutations (mainly KRAS, NRAS, MAP2K1 or BRAF) in the experimental arm but not the control arm. In Cohort 3 (n = 5), PFS ranged from 3.6 to 14.7 months versus 4.0 to 5.4 months in the experimental and control arms, respectively. In Cohort 4 (n = 99), PFS was shorter in the experimental arm (hazard ratio, 1.44; 95% confidence intervals 0.90–2.29; P = 0.128). Conclusions Vemurafenib plus cetuximab plus 5-FU/LV warrants further investigation as first-line maintenance treatment for BRAFmut mCRC. MAPK-pathway emergent genomic alterations may offer novel therapeutic opportunities in BRAFmut mCRC. Cobimetinib plus atezolizumab had an unfavourable benefit:risk ratio in HER2‒/MSS/BRAFwt mCRC. New strategies are required to increase the susceptibility of MSS mCRC to immunotherapy.This work was supported by F. Hoffmann-La Roche Ltd

MODUL cohort 2: an adaptable, randomized, signal-seeking trial of fluoropyrimidine plus bevacizumab with or without atezolizumab maintenance therapy for BRAFwt metastatic colorectal cancer

Atezolizumab; Bevacizumab; Metastatic colorectal cancerAtezolizumab; Bevacizumab; Cáncer colorrectal metastásicoAtezolizumab; Bevacizumab; Càncer colorectal metastàticBackground MODUL is an adaptable, signal-seeking trial designed to test novel agents in predefined patient subgroups in first-line metastatic colorectal cancer (mCRC). Patients and methods Patients with measurable, unresectable, previously untreated mCRC received induction with ≤8 cycles of FOLFOX + bevacizumab followed by randomization to maintenance treatment comprising control [fluoropyrimidine (FP)/bevacizumab: 5-fluorouracil 1600-2400 mg/m2 46-h intravenous (i.v.) infusion day 1 q2 weeks plus leucovorin 400 mg/m2 2-h infusion i.v. day 1 q2 weeks or capecitabine 1000 mg/m2 b.i.d. orally days 1-14 every 21 days; bevacizumab 5 mg/kg 15-30-min i.v. infusion q2 weeks] or experimental treatment in one of four biomarker-driven cohorts. In patients with BRAF wild-type (BRAFwt) tumors (cohort 2), experimental treatment was FP/bevacizumab + atezolizumab (800 mg 60-min i.v. infusion q2 weeks). Primary efficacy endpoint was progression-free survival (PFS; intent-to-treat population). Enrollment is complete; efficacy and safety findings from cohort 2 are presented. Results Four hundred and forty-five patients with BRAFwt mCRC were randomized (2 : 1) to maintenance in cohort 2. At a median follow-up of 10.5 months, PFS outcome hypothesis was not met [hazard ratio (HR) 0.92; 95% confidence interval (CI) 0.72-1.17; P = 0.48]; overall survival (OS) was immature. At a median follow-up of 20.3 months (2-year survival follow-up), PFS benefit was also not met (HR 0.95; 95% CI 0.77-1.18; P = 0.666); OS HR with nearly two-thirds of patients with events was 0.83 (95% CI 0.65-1.05; P = 0.117). No new safety signals were identified. The most common grade ≥3 treatment-emergent adverse events (TEAEs) for experimental versus control arms were hypertension (6.1% versus 4.2%), diarrhea (3.1% versus 2.1%), and palmar-plantar erythrodysesthesia syndrome (1.0% versus 2.5%). Four patients experienced TEAEs with fatal outcome, two were study treatment-related: hepatic failure (experimental arm) and large intestine perforation (control arm; bevacizumab-related). Conclusions Adding atezolizumab to FP/bevacizumab as first-line maintenance treatment after FOLFOX + bevacizumab induction for BRAFwt mCRC did not improve efficacy outcomes.This work was supported by F. Hoffmann-La Roche Ltd (no grant number). The sponsor was involved in the study design and was responsible for the overall study management (monitoring), drug supply, data management, statistical analysis, and drug safety process. The Trial Master Files are maintained electronically by the sponsor. The sponsor was involved in the writing of this report, alongside the authors, all of whom had access to the raw data. The corresponding author had full access to all of the data and the final responsibility for submitting the article for publication on behalf of all authors

Predictive control co-design for enhancing flexibility in residential housing with battery degradation

Buildings are responsible for about a quarter of global energy-related CO2 emissions. Consequently, the decarbonisation of the housing stock is essential in achieving net-zero carbon emissions. Global decarbonisation targets can be achieved through increased efficiency in using energy generated by intermittent resources. The paper presents a co-design framework for simultaneous optimal design and operation of residential buildings using Model Predictive Control (MPC). The framework is capable of explicitly taking into account operational constraints and pushing the system to its efficiency and performance limits in an integrated fashion. The optimality criterion minimises system cost considering time-varying electricity prices and battery degradation. A case study illustrates the potential of co-design in enhancing flexibility and self-sufficiency of a system operating under different conditions. Specifically, numerical results from a low-fidelity model show substantial carbon emission reduction and bill savings compared to an a-priori sizing approach

Analysis of surface waves generated on subwavelength-structured silver films

Using transmission electron microscopy (TEM) to analyse the physical-chemical surface properties of subwavlength structured silver films and finite-difference time-domain (FDTD) numerical simulations of the optical response of these structures to plane-wave excitation, we report on the origin and nature of the persistent surface waves generated by a single slit-groove motif and recently measured by far-field optical interferometry. The surface analysis shows that the silver films are free of detectable oxide or sulfide contaminants, and the numerical simulations show very good agreement with the results previously reported.Comment: 9 Figure

Counting niches: Abundance- by- trait patterns reveal niche partitioning in a Neotropical forest

Tropical forests challenge us to understand biodiversity, as numerous seemingly similar species persist on only a handful of shared resources. Recent ecological theory posits that biodiversity is sustained by a combination of species differences reducing interspecific competition and species similarities increasing time to competitive exclusion. Together, these mechanisms counterintuitively predict that competing species should cluster by traits, in contrast with traditional expectations of trait overdispersion. Here, we show for the first time that trees in a tropical forest exhibit a clustering pattern. In a 50- ha plot on Barro Colorado Island in Panama, species abundances exhibit clusters in two traits connected to light capture strategy, suggesting that competition for light structures community composition. Notably, we find four clusters by maximum height, quantitatively supporting the classical grouping of Neotropical woody plants into shrubs, understory, midstory, and canopy layers.Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/155460/1/ecy3019.pdfhttps://deepblue.lib.umich.edu/bitstream/2027.42/155460/2/ecy3019-sup-0001-AppendixS1.pdfhttps://deepblue.lib.umich.edu/bitstream/2027.42/155460/3/ecy3019_am.pd

Velocity measurements for a solar active region fan loop from Hinode/EIS observations

The velocity pattern of a fan loop structure within a solar active region over the temperature range 0.15-1.5 MK is derived using data from the EUV Imaging Spectrometer (EIS) on board the Hinode satellite. The loop is aligned towards the observer's line-of-sight and shows downflows (redshifts) of around 15 km/s up to a temperature of 0.8 MK, but for temperatures of 1.0 MK and above the measured velocity shifts are consistent with no net flow. This velocity result applies over a projected spatial distance of 9 Mm and demonstrates that the cooler, redshifted plasma is physically disconnected from the hotter, stationary plasma. A scenario in which the fan loops consist of at least two groups of "strands" - one cooler and downflowing, the other hotter and stationary -- is suggested. The cooler strands may represent a later evolutionary stage of the hotter strands. A density diagnostic of Mg VII was used to show that the electron density at around 0.8 MK falls from 3.2 x 10^9 cm^-3 at the loop base, to 5.0 x 10^8 cm^-3 at a projected height of 15 Mm. A filling factor of 0.2 is found at temperatures close to the formation temperature of Mg VII (0.8 MK), confirming that the cooler, downflowing plasma occupies only a fraction of the apparent loop volume. The fan loop is rooted within a so-called "outflow region" that displays low intensity and blueshifts of up to 25 km/s in Fe XII 195.12 A (formed at 1.5 MK), in contrast to the loop's redshifts of 15 km/s at 0.8 MK. A new technique for obtaining an absolute wavelength calibration for the EIS instrument is presented and an instrumental effect, possibly related to a distorted point spread function, that affects velocity measurements is identified.Comment: 42 pages, 15 figures, submitted to Ap

Adapting the EQ-5D-3L for adults with mild to moderate learning disabilities

Background Approximately 1.5 million adults in the UK have a learning disability. The difference between age at death for this group and the general population is 26 years for females and 22 years for males. The NHS Long Term Plan (January 2019) recognises learning disabilities as a clinical priority area. People with a learning disability are often excluded from research by design or lack of reasonable adjustments, and self-reported health status/health-related quality of life questionnaires such as the EQ-5D are often not appropriate for this population. Here, we systematically examine the EQ-5D-3L (its wording, content, and format) using qualitative methods to inform the adaption of the measure for use with adults with mild to moderate learning disabilities. Methods Think-aloud interviews with carers/advocates of learning-disabled adults were undertaken to explore the difficulties with completing the EQ-5D-3L. Alternative wording, language, structure, and images were developed using focus groups, stakeholder reference groups, and an expert panel. Data analysis followed a framework method. Results The dimensions and levels within the EQ-5D-3L were deemed appropriate for adults with mild to moderate learning disabilities. Consensus on wording, structure, and images was reached through an iterative process, and an adapted version of the EQ-5D-3L was finalised. Conclusion The EQ-5D-3L adapted for adults with mild to moderate intellectual/learning disabilities can facilitate measurement of self-reported health status. Research is underway to assess the potential use of the adaptation for economic evaluation

Handbook for SDG-Aligned Food Companies: Four Pillar Framework Standards

The world food system is in crisis. Outright hunger, unhealthy diets and malnutrition occur parallel to food losses and waste. Farming families in poor countries suffer from extreme poverty. And food production is environmentally unsustainable and increasingly vulnerable to extreme weather events caused by climate change. A historic change of direction is needed to bring about a new era of food system sustainability. Our work aims to help companies, investors and other stakeholders move towards a more sustainable food system that is aligned with the Sustainable Development Goals. Transforming the world food system to achieve sustainability in all its dimensions is a major challenge. Achieving the Sustainable Development Goals will require managing major changes to the global food system responsibly, involving hundreds of millions of farmers and their families, global supply chains, thousands of food producing companies, diverse food production systems and local ecologies, food processing and a great diversity of food traditions and cultures. Food companies are engaged in food production, trade, processing, and consumer sales around the world. While they have distinct roles “from farm to fork,” they all share the same responsibility: to be part of the global transformation towards food system sustainability. For more on CCSI and SDSN’s work on corporate alignment with the Sustainable Development Goals, see our framework defining SDG-aligned business practices in the energy sector