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PURPOSE: Despite advances in systemic therapy, outcomes of patients with gastric cancer (GC) peritoneal carcinomatosis (PC) remain poor, in part because of poor penetrance of systemic therapy into peritoneal metastasis due to the plasma-peritoneal barrier and anarchic intra-tumoral circulation. Hence, regional treatment approach with administration of chemotherapy directly into the peritoneal cavity (intraperitoneal, IP) under various conditions, combined with or without cytoreductive surgery (CRS) has remained an area of significant research interest. The purpose of this review is to provide high-level evidence for regional treatment approaches in the management of GCPC with limited peritoneal disease. METHODS: A review of the current literature and ongoing clinical trials for regional IP therapies for GCPC was performed. Studies included in this review comprise of phase III randomized controlled trials, non-randomized phase II studies, high-impact retrospective studies, and active ongoing clinical trials for each available IP modality. RESULTS: The three common IP approaches are heated intraperitoneal chemotherapy (HIPEC), normothermic intraperitoneal chemotherapy (NIPEC) and more recently introduced, pressurized intraperitoneal aerosolized chemotherapy (PIPAC). These IP approaches have been combined with systemic therapy and/or CRS with varying degrees of promising results, demonstrating evidence of improvements in survival rates and peritoneal disease control. Patient selection, optimization of systemic therapy, and completeness of cytoreduction have emerged as major factors influencing the design of contemporary and ongoing trials. CONCLUSION: IP chemotherapy has a clear role in the management of patients with GCPC, and when combined with CRS in appropriately selected patients has the potential to significantly improve survival. Ongoing and upcoming IP therapy clinical trials hold great promise to shape the treatment paradigm for GCPC.

Unreinforced masonry structures, constituting a significant portion of the global building stock, hold substantial cultural and architectural value in many countries. Often home to a considerable population in developing nations, these structures have faced severe damage from recent large-scale earthquakes. Consequently, retrofitting these structures has emerged as a critical global concern demanding immediate attention. This thesis focuses on the pivotal investigation of how incorporating bed joint reinforcement and employing glass fiber composites influences the behavior of masonry walls under seismic loads. The research aims to contribute valuable insights to the ongoing discussion on enhancing the seismic resilience of these structures through innovative reinforcement techniques.In this study, a simplified 3D micro modeling approach has been developed to assess the behavior of masonry walls under earthquake conditions. This model comprehensively considers most of the crucial factors influencing wall behavior and is solved with general-purpose finite element software. To simulate the nonlinear behavior of concrete, the study utilizes the Concrete Damage Plasticity model provided by Abaqus. The traction–separation behavior of the cohesive element is incorporated to model the mortar joints. The 3D finite element model adopted in this study utilizes solid elements (C3D8R) to define the blocks.In summary, the evaluation of different reinforcement techniques for masonry walls reveals distinct outcomes. The implementation of bed joint reinforcement results in stress concentration primarily occurring at the bottom of the wall, leading to an undesirable failure mode. Similarly, using adhesive, the onset of plastic equivalent strains commences at the toe and stretches towards the opposite toe, yielding an unfavorable pattern. On the other hand, the employment of vertical fibers demonstrates effectiveness in uniformly dispersing the plastic equivalent strains throughout th

The critical behavior of the order-disorder phase transition in the buckled dimer structure of the Si(001) surface is investigated both theoretically by means of first-principles calculations and experimentally by spot profile analysis low-energy electron diffraction (SPA-LEED). We use density functional theory (DFT) with three different functionals commonly used for Si to determine the coupling constants of an effective lattice Hamiltonian describing the dimer interactions. Experimentally, the phase transition from the low-temperature c(4×2)- to the high-temperature p(2×1)-reconstructed surface is followed through the intensity and width of the superstructure spots within the temperature range 78–400K. Near the critical temperature Tc = 190.6K, we observe universal critical behavior of spot intensities and correlation lengths, which falls into the universality class of the two-dimensional (2D) Ising model. From the ratio of correlation lengths along and across the dimer rows we determine effective nearest-neighbor couplings of an anisotropic 2D Ising model, J = (−24.9 ± 0.9stat ± 1.3sys )meV and J⊥ = (−0.8 ± 0.1stat )meV.We find that the experimentally determined coupling constants of the Ising model can be reconciled with those of the more complex lattice Hamiltonian from DFT when the critical behavior is of primary interest. The anisotropy of the interactions derived from the experimental data via the 2D Ising model is best matched by DFT calculations using the PBEsol functional. The trends in the calculated anisotropy are consistent with the surface stress anisotropy predicted by the DFT functionals, pointing towards the role of surface stress reduction as a driving force for establishing the c(4×2)-reconstructed ground state.

Unreinforced masonry structures, constituting a significant portion of the global building stock, hold substantial cultural and architectural value in many countries. Often home to a considerable population in developing nations, these structures have faced severe damage from recent large-scale earthquakes. Consequently, retrofitting these structures has emerged as a critical global concern demanding immediate attention. This thesis focuses on the pivotal investigation of how incorporating bed joint reinforcement and employing glass fiber composites influences the behavior of masonry walls under seismic loads. The research aims to contribute valuable insights to the ongoing discussion on enhancing the seismic resilience of these structures through innovative reinforcement techniques.In this study, a simplified 3D micro modeling approach has been developed to assess the behavior of masonry walls under earthquake conditions. This model comprehensively considers most of the crucial factors influencing wall behavior and is solved with general-purpose finite element software. To simulate the nonlinear behavior of concrete, the study utilizes the Concrete Damage Plasticity model provided by Abaqus. The traction–separation behavior of the cohesive element is incorporated to model the mortar joints. The 3D finite element model adopted in this study utilizes solid elements (C3D8R) to define the blocks.In summary, the evaluation of different reinforcement techniques for masonry walls reveals distinct outcomes. The implementation of bed joint reinforcement results in stress concentration primarily occurring at the bottom of the wall, leading to an undesirable failure mode. Similarly, using adhesive, the onset of plastic equivalent strains commences at the toe and stretches towards the opposite toe, yielding an unfavorable pattern. On the other hand, the employment of vertical fibers demonstrates effectiveness in uniformly dispersing the plastic equivalent strains throughout th

Printed circuit boards (PCBs) are an integral part of electronic systems. Hence, verifying their physical integrity in the presence of supply chain attacks (e.g., tampering and counterfeiting) is of utmost importance. Recently, tamper detection techniques grounded in impedance characterization of PCB's Power Delivery Network (PDN) have gained prominence due to their global detection coverage, non-invasive, and low-cost nature. Similar to other physical verification methods, these techniques rely on the existence of a physical golden sample for signature comparisons. However, having access to a physical golden sample for golden signature extraction is not feasible in many real-world scenarios. In this work, we assess the feasibility of eliminating a physical golden sample and replacing it with a simulated golden signature obtained by the PCB design files. By performing extensive simulation and measurements on an in-house designed PCB, we demonstrate how the parasitic impedance of the PCB components plays a major role in reaching a successful verification. Based on the obtained results and using statistical metrics, we show that we can mitigate the discrepancy between collected signatures from simulation and measurements.

Physical side-channel attacks can compromise the security of integrated circuits. Most physical side-channel attacks (e.g., power or electromagnetic) exploit the dynamic behavior of a chip, typically manifesting as changes in current consumption or voltage fluctuations where algorithmic countermeasures, such as masking, can effectively mitigate them. However, as demonstrated recently, these mitigation techniques are not entirely effective against backscattered side-channel attacks such as impedance analysis. In the case of an impedance attack, an adversary exploits the data-dependent impedance variations of the chip power delivery network (PDN) to extract secret information. In this work, we introduce RandOhm, which exploits a moving target defense (MTD) strategy based on the partial reconfiguration (PR) feature of mainstream FPGAs and programmable SoCs to defend against impedance side-channel attacks. We demonstrate that the information leakage through the PDN impedance could be significantly reduced via runtime reconfiguration of the secret-sensitive parts of the circuitry. Hence, by constantly randomizing the placement and routing of the circuit, one can decorrelate the data-dependent computation from the impedance value. Moreover, in contrast to existing PR-based countermeasures, RandOhm deploys open-source bitstream manipulation tools on programmable SoCs to speed up the randomization and provide real-time protection. To validate our claims, we apply RandOhm to AES ciphers realized on 28-nm FPGAs. We analyze the resiliency of our approach by performing non-profiled and profiled impedance analysis attacks and investigate the overhead of our mitigation in terms of delay and performance.

The critical behavior of the order-disorder phase transition in the buckled dimer structure of the Si(001) surface is investigated both theoretically by means of first-principles calculations and experimentally by spot profile analysis low-energy electron diffraction (SPA-LEED). We use density functional theory (DFT) with three different functionals commonly used for Si to determine the coupling constants of an effective lattice Hamiltonian describing the dimer interactions. Experimentally, the phase transition from the low-temperature c(4×2)- to the high-temperature p(2×1)-reconstructed surface is followed through the intensity and width of the superstructure spots within the temperature range 78–400K. Near the critical temperature Tc = 190.6K, we observe universal critical behavior of spot intensities and correlation lengths, which falls into the universality class of the two-dimensional (2D) Ising model. From the ratio of correlation lengths along and across the dimer rows we determine effective nearest-neighbor couplings of an anisotropic 2D Ising model, J = (−24.9 ± 0.9stat ± 1.3sys )meV and J⊥ = (−0.8 ± 0.1stat )meV.We find that the experimentally determined coupling constants of the Ising model can be reconciled with those of the more complex lattice Hamiltonian from DFT when the critical behavior is of primary interest. The anisotropy of the interactions derived from the experimental data via the 2D Ising model is best matched by DFT calculations using the PBEsol functional. The trends in the calculated anisotropy are consistent with the surface stress anisotropy predicted by the DFT functionals, pointing towards the role of surface stress reduction as a driving force for establishing the c(4×2)-reconstructed ground state.

The critical behavior of the order-disorder phase transition in the buckled dimer structure of the Si(001) surface is investigated both theoretically by means of first-principles calculations and experimentally by spot profile analysis low-energy electron diffraction (SPA-LEED). We use density functional theory (DFT) with three different functionals commonly used for Si to determine the coupling constants of an effective lattice Hamiltonian describing the dimer interactions. Experimentally, the phase transition from the low-temperature c(4×2)- to the high-temperature p(2×1)-reconstructed surface is followed through the intensity and width of the superstructure spots within the temperature range 78–400K. Near the critical temperature Tc = 190.6K, we observe universal critical behavior of spot intensities and correlation lengths, which falls into the universality class of the two-dimensional (2D) Ising model. From the ratio of correlation lengths along and across the dimer rows we determine effective nearest-neighbor couplings of an anisotropic 2D Ising model, J = (−24.9 ± 0.9stat ± 1.3sys )meV and J⊥ = (−0.8 ± 0.1stat )meV.We find that the experimentally determined coupling constants of the Ising model can be reconciled with those of the more complex lattice Hamiltonian from DFT when the critical behavior is of primary interest. The anisotropy of the interactions derived from the experimental data via the 2D Ising model is best matched by DFT calculations using the PBEsol functional. The trends in the calculated anisotropy are consistent with the surface stress anisotropy predicted by the DFT functionals, pointing towards the role of surface stress reduction as a driving force for establishing the c(4×2)-reconstructed ground state.

Syftet med studien är att analysera hur personalomsättningen inom en specifik avdelning i akutvården påverkar personalens upplevelser av samhörighet. Målet är att bilda en nyanserad förståelse för de faktorer som påverkar samhörigheter och identifiera eventuella utmaningar som kan uppstå på grund av den höga personalomsättningen. Arbetet är en kvalitativ studie där vi utfört totalt sju semistrukturerade intervjuer med nuvarande och tidigare anställda samt en chef på avdelningen. Vi har kompletterat de kvalitativa metoderna med kvantitativ data i form av statistik över avdelningens personalomsättning för de senaste fem åren. Två tydliga grupperingar av personalen har bildats inom avdelningen - en bestående av långvariga anställda och en bestående av nyanställda. Den höga personalomsättningen inom avdelningen påverkar inte samhörigheten som förväntat då studien avslöjar att det i själva verket existerar en relativt god samhörighet inom vardera gruppering, men att samhörigheten mellan grupperna är i princip obefintlig. Faktorer som skiftarbete och gemensamma utmaningar främjar samhörigheten, medan faktorer som avgränsade arbetsområden och generationsskillnader utgör hinder för samhörigheten.

Driven by a need for ever increasing chip performance and inclusion of innovative features, a growing number of semiconductor companies are opting for all-inclusive System-on-Chip (SoC) architectures. Although Moore's Law has been able to keep up with the demand for more complex logic, manufacturing large dies still poses a challenge. Increasingly the solution adopted to minimize the impact of silicon defects on manufacturing yield has been to split a design into multiple smaller dies called chiplets which are then brought together on a silicon interposer. Advanced 2.5D and 3D packaging techniques that enable this kind of integration also promise increased power efficiency and opportunities for heterogeneous integration. However, despite their advantages, chiplets are not without issues. Apart from manufacturing challenges that come with new packaging techniques, disaggregating a design into multiple logically and physically separate dies introduces new threats, including the possibility of tampering with and probing exposed data lines. In this paper we evaluate the exposure of chiplets to probing by applying laser contactless probing techniques to a chiplet-based AMD/Xilinx VU9P FPGA. First, we identify and map interposer wire drivers and show that probing them is easier compared to probing internal nodes. Lastly, we demonstrate that delay-based sensors, which can be used to protect against physical probes, are insufficient to protect against laser probing as the delay change due to laser probing is only 0.792ps even at 100\% laser power.

The security of integrated circuits (ICs) can be broken by sophisticated physical attacks relying on failure analysis methods. Optical probing is one of the most prominent examples of such attacks, which can be accomplished in a matter of days, even with limited knowledge of the IC under attack. Unfortunately, few countermeasures are proposed in the literature, and none has been fabricated and tested in practice. These countermeasures usually require changing the standard cell libraries and, thus, are incompatible with digital and programmable platforms, such as field programmable gate arrays (FPGAs). In this work, we shift our attention from preventing the attack to detecting and responding to it. We introduce LaserEscape, the first fully digital and FPGA-compatible countermeasure to detect and mitigate optical probing attacks. LaserEscape incorporates digital delay-based sensors to reliably detect the physical alteration on the fabric caused by laser beam irradiations in real time. Furthermore, as a response to the attack, LaserEscape deploys real-time hiding approaches using randomized hardware reconfigurability. It realizes 1) moving target defense (MTD) to physically move the sensitive circuity under attack out of the probing field of focus to protect secret keys and 2) polymorphism to logically obfuscate the functionality of the targeted circuit to counter function extraction and reverse engineering attempts. We demonstrate the effectiveness and resiliency of our approach by performing optical probing attacks on protected and unprotected designs on a 28-nm FPGA. Our results show that optical probing attacks can be reliably detected and mitigated without interrupting the chip's operation.

Background: The extent to which health care systems have adapted to the COVID-19 pandemic to provide necessary cardiac diagnostic services is unknown. Objectives: The aim of this study was to determine the impact of the pandemic on cardiac testing practices, volumes and types of diagnostic services, and perceived psychological stress to health care providers worldwide. Methods: The International Atomic Energy Agency conducted a worldwide survey assessing alterations from baseline in cardiovascular diagnostic care at the pandemic's onset and 1 year later. Multivariable regression was used to determine factors associated with procedure volume recovery. Results: Surveys were submitted from 669 centers in 107 countries. Worldwide reduction in cardiac procedure volumes of 64% from March 2019 to April 2020 recovered by April 2021 in high- and upper middle-income countries (recovery rates of 108% and 99%) but remained depressed in lower middle- and low-income countries (46% and 30% recovery). Although stress testing was used 12% less frequently in 2021 than in 2019, coronary computed tomographic angiography was used 14% more, a trend also seen for other advanced cardiac imaging modalities (positron emission tomography and magnetic resonance; 22%-25% increases). Pandemic-related psychological stress was estimated to have affected nearly 40% of staff, impacting patient care at 78% of sites. In multivariable regression, only lower-income status and physicians’ psychological stress were significant in predicting recovery of cardiac testing. Conclusions: Cardiac diagnostic testing has yet to recover to prepandemic levels in lower-income countries. Worldwide, the decrease in standard stress testing is offset by greater use of advanced cardiac imaging modalities. Pandemic-related psychological stress among providers is widespread and associated with poor recovery of cardiac testing.

In the world of mobile applications, there is no lack of frameworks and languages to use for development. One of the most used frameworks is React Native, which builds on React for web browsers. The React Native framework allows the developer to write the application in JavaScript, and run the application on iOS or Android devices. As the market for mobile applications expands, the time it takes to develop an application is under pressure, and a framework allowing for one codebase for two applications can save time and money. Deedster is a company that provides a mobile application where the user can learn about climate change and perform small tasks, deeds, that give a positive impact on the environment. A common request from the users is the automatization of completion of deeds. This thesis creates two implementations of a QR-code scanning application for completion of deeds, one with Swift and one with React Native, and compares the experiences during development and the results of the implementation. The evaluation uses both a quantitative and a qualitative analysis. The produced application fulfilled most of the requirements, including the scanning of a QR-code to open the application, an authentication process and the completion of a deed with confirmation for the user. The execution times for the two implementations did not differ largely, but the measurements of the application launch time proved flawed in design due to the difference in measurement technique between the two implementations. When it came to the development process, the React Native framework provided major difficulties with configuration and dependencies, resulting in difficulties when locating the source of errors. The launching process for the Swift application required some manual configurations that proved difficult such as creating certificates, while the React Native implementation used Expo to convert the project to a launchable file format which created all required files for the de, För applikationsutveckling för mobiler finns det en uppsjö av språk och ramverk för att underlätta utvecklingsprocessen. Ett av de vanligaste ramverken är React Native som bygger på React för webbläsare. React Native-ramverket låter utvecklare skriva koden i JavaScript, men köra applikationen på både iOS- och Android-enheter. I takt med att marknaden för mobilapplikationer växer, sätts det högre press på kortare utvecklingsfaser och snabbare lansering. För att underlätta processen och spara tid och pengar kan React Native vara en bra lösning. Deedster är ett företag som erbjuder en mobilapplikation där användaren kan lära sig om klimatförändringar och utföra små uppdrag, deeds, som ger en positiv påverkan på klimatet. En vanlig förfrågan från användare är ett sätt att automatisera avklarandet av deeds. Den här uppsatsen skapar två implementationer av en applikation som scannar en QR-kod för att markera en deed som avklarad. Den ena byggs med Swift och den andra med React Native och syftar till att jämföra utvecklingsprocessen och den resulterande applikationen. Evalueringen sker med både en kvalitativ och en kvantitativ analys. Den färdiga applikationen uppfyllde de flesta kraven som Deedster ställt, inklusive att appen öppnas genom att scanna en QR-kod, en användare kan autentisera sig, klicka för att markera en deed som klar och få bekräftelse från appen om att det är klart. Exekveringstiderna för de två implementationerna varierade inte märkbart, men mätningarna för starttiden för applikationerna visade sig bristfällig då mättekniken för de två apparna inte blev jämförbar. Gällande utvecklingsprocessen resulterade användandet av React Native i stora problem med konfigurationer och versionskompatibilitet vilket gjorde felsökning svårt. Lanseringsprocessen för Swift-appen krävde en del manuell konfigurering med till exempel certifikat, medan React Native implementationen använde Expo för att konvertera React Native-projektet till ett lanserbart filformat som skapad

As the core component of all organs, the extracellular matrix (ECM) is an interlocking macromolecular meshwork of proteins, glycoproteins, and proteoglycans that provides mechanical support to cells and tissues. In cancer, the ECM can be remodelled in response to environmental cues, and it controls a plethora of cellular functions, including metabolism, cell polarity, migration, and proliferation, to sustain and support oncogenesis. The biophysical and biochemical properties of the ECM, such as its structural arrangement and being a reservoir for bioactive molecules, control several intra- and intercellular signalling pathways and induce cytoskeletal changes that alter cell shapes, behaviour, and viability. Desmoplasia is a major component of solid tumours. The abnormal deposition and composition of the tumour matrix lead to biochemical and biomechanical alterations that determine disease development and resistance to treatment. This review summarises the complex roles of ECM in cancer and highlights the possible therapeutic targets and how to potentially remodel the dysregulated ECM in the future. Furthering our understanding of the ECM in cancer is important as the modification of the ECM will probably become an important tool in the characterisation of individual tumours and personalised treatment options.

UNLABELLED: Acute myeloid leukemia (AML) is fueled by leukemic stem cells (LSC) whose determinants are challenging to discern from hematopoietic stem cells (HSC) or uncover by approaches focused on general cell properties. We have identified a set of RNA-binding proteins (RBP) selectively enriched in human AML LSCs. Using an in vivo two-step CRISPR-Cas9 screen to assay stem cell functionality, we found 32 RBPs essential for LSCs in MLL-AF9;NrasG12D AML. Loss-of-function approaches targeting key hit RBP ELAVL1 compromised LSC-driven in vivo leukemic reconstitution, and selectively depleted primitive malignant versus healthy cells. Integrative multiomics revealed differentiation, splicing, and mitochondrial metabolism as key features defining the leukemic ELAVL1-mRNA interactome with mitochondrial import protein, TOMM34, being a direct ELAVL1-stabilized target whose repression impairs AML propagation. Altogether, using a stem cell-adapted in vivo CRISPR screen, this work demonstrates pervasive reliance on RBPs as regulators of LSCs and highlights their potential as therapeutic targets in AML. SIGNIFICANCE: LSC-targeted therapies remain a significant unmet need in AML. We developed a stem-cell-adapted in vivo CRISPR screen to identify key LSC drivers. We uncover widespread RNA-binding protein dependencies in LSCs, including ELAVL1, which we identify as a novel therapeutic vulnerability through its regulation of mitochondrial metabolism. This article is highlighted in the In This Issue feature, p. 171.

In the world of mobile applications, there is no lack of frameworks and languages to use for development. One of the most used frameworks is React Native, which builds on React for web browsers. The React Native framework allows the developer to write the application in JavaScript, and run the application on iOS or Android devices. As the market for mobile applications expands, the time it takes to develop an application is under pressure, and a framework allowing for one codebase for two applications can save time and money. Deedster is a company that provides a mobile application where the user can learn about climate change and perform small tasks, deeds, that give a positive impact on the environment. A common request from the users is the automatization of completion of deeds. This thesis creates two implementations of a QR-code scanning application for completion of deeds, one with Swift and one with React Native, and compares the experiences during development and the results of the implementation. The evaluation uses both a quantitative and a qualitative analysis. The produced application fulfilled most of the requirements, including the scanning of a QR-code to open the application, an authentication process and the completion of a deed with confirmation for the user. The execution times for the two implementations did not differ largely, but the measurements of the application launch time proved flawed in design due to the difference in measurement technique between the two implementations. When it came to the development process, the React Native framework provided major difficulties with configuration and dependencies, resulting in difficulties when locating the source of errors. The launching process for the Swift application required some manual configurations that proved difficult such as creating certificates, while the React Native implementation used Expo to convert the project to a launchable file format which created all required files for the de, För applikationsutveckling för mobiler finns det en uppsjö av språk och ramverk för att underlätta utvecklingsprocessen. Ett av de vanligaste ramverken är React Native som bygger på React för webbläsare. React Native-ramverket låter utvecklare skriva koden i JavaScript, men köra applikationen på både iOS- och Android-enheter. I takt med att marknaden för mobilapplikationer växer, sätts det högre press på kortare utvecklingsfaser och snabbare lansering. För att underlätta processen och spara tid och pengar kan React Native vara en bra lösning. Deedster är ett företag som erbjuder en mobilapplikation där användaren kan lära sig om klimatförändringar och utföra små uppdrag, deeds, som ger en positiv påverkan på klimatet. En vanlig förfrågan från användare är ett sätt att automatisera avklarandet av deeds. Den här uppsatsen skapar två implementationer av en applikation som scannar en QR-kod för att markera en deed som avklarad. Den ena byggs med Swift och den andra med React Native och syftar till att jämföra utvecklingsprocessen och den resulterande applikationen. Evalueringen sker med både en kvalitativ och en kvantitativ analys. Den färdiga applikationen uppfyllde de flesta kraven som Deedster ställt, inklusive att appen öppnas genom att scanna en QR-kod, en användare kan autentisera sig, klicka för att markera en deed som klar och få bekräftelse från appen om att det är klart. Exekveringstiderna för de två implementationerna varierade inte märkbart, men mätningarna för starttiden för applikationerna visade sig bristfällig då mättekniken för de två apparna inte blev jämförbar. Gällande utvecklingsprocessen resulterade användandet av React Native i stora problem med konfigurationer och versionskompatibilitet vilket gjorde felsökning svårt. Lanseringsprocessen för Swift-appen krävde en del manuell konfigurering med till exempel certifikat, medan React Native implementationen använde Expo för att konvertera React Native-projektet till ett lanserbart filformat som skapad

Background In colorectal cancer, the effects of immune checkpoint inhibitors are mostly limited to patients with deficient mismatch repair tumors, characterized by a high grade infiltration of CD8+T cells. Interventions aimed at increasing intratumoral CD8+T-cell infiltration in proficient mismatch repair tumors are lacking. Methods We conducted a proof of concept phase 1/2 clinical trial, where patients with non-metastasizing sigmoid or rectal cancer, scheduled for curative intended surgery, were treated with an endoscopic intratumorally administered neoadjuvant influenza vaccine. Blood and tumor samples were collected before the injection and at the time of surgery. The primary outcome was safety of the intervention. Evaluation of pathological tumor regression grade, immunohistochemistry, flow cytometry of blood, tissue bulk transcriptional analyses, and spatial protein profiling of tumor regions were all secondary outcomes. Results A total of 10 patients were included in the trial. Median patient age was 70 years (range 54-78), with 30% women. All patients had proficient mismatch repair Union of International Cancer Control stage I-III tumors. No endoscopic safety events occurred, with all patients undergoing curative surgery as scheduled (median 9 days after intervention). Increased CD8+T-cell tumor infiltration was evident after vaccination (median 73 vs 315 cells/mm 2, p<0.05), along with significant downregulation of messenger RNA gene expression related to neutrophils and upregulation of transcripts encoding cytotoxic functions. Spatial protein analysis showed significant local upregulation of programmed death-ligand 1 (PD-L1) (adjusted p value<0.05) and downregulation of FOXP3 (adjusted p value<0.05). Conclusions Neoadjuvant intratumoral influenza vaccine treatment in this cohort was demonstrated to be safe and feasible, and to induce CD8+T-cell infiltration and upregulation of PD-L1 proficient mismatch repair sigmoid and rectal tumors. Definiti

Background In colorectal cancer, the effects of immune checkpoint inhibitors are mostly limited to patients with deficient mismatch repair tumors, characterized by a high grade infiltration of CD8+T cells. Interventions aimed at increasing intratumoral CD8+T-cell infiltration in proficient mismatch repair tumors are lacking.Methods We conducted a proof of concept phase 1/2 clinical trial, where patients with non-metastasizing sigmoid or rectal cancer, scheduled for curative intended surgery, were treated with an endoscopic intratumorally administered neoadjuvant influenza vaccine. Blood and tumor samples were collected before the injection and at the time of surgery. The primary outcome was safety of the intervention. Evaluation of pathological tumor regression grade, immunohistochemistry, flow cytometry of blood, tissue bulk transcriptional analyses, and spatial protein profiling of tumor regions were all secondary outcomes.Results A total of 10 patients were included in the trial. Median patient age was 70 years (range 54–78), with 30% women. All patients had proficient mismatch repair Union of International Cancer Control stage I–III tumors. No endoscopic safety events occurred, with all patients undergoing curative surgery as scheduled (median 9 days after intervention). Increased CD8+T-cell tumor infiltration was evident after vaccination (median 73 vs 315 cells/mm2, p<0.05), along with significant downregulation of messenger RNA gene expression related to neutrophils and upregulation of transcripts encoding cytotoxic functions. Spatial protein analysis showed significant local upregulation of programmed death-ligand 1 (PD-L1) (adjusted p value<0.05) and downregulation of FOXP3 (adjusted p value<0.05).Conclusions Neoadjuvant intratumoral influenza vaccine treatment in this cohort was demonstrated to be safe and feasible, and to induce CD8+T-cell infil

Solar and stellar magnetic patches (i.e., magnetic fluxes that reach the surface from the interior) are believed to be the primary sources of a star's atmospheric conditions. Hence, detecting and identifying these features (also known as magnetic elements) are among the essential topics in the community. Here, we apply the complex network approach to recognize the solar magnetic patches. For this purpose, we use the line-of-sight magnetograms provided by the Helioseismic and Magnetic Imager on board the Solar Dynamic Observatory. We construct the magnetic network following a specific visibility graph condition between pairs of pixels with opposite polarities and search for possible links between these regions. The complex network approach also provides the ability to rank the patches based on their connectivity (i.e., degree of nodes) and importance (i.e., PageRank). The use of the developed algorithm in the identification of magnetic patches is examined by tracking the features in consecutive frames, as well as making a comparison with the other approaches to identification. We find that this method could conveniently identify features regardless of their sizes. For small-scale (one or two pixels) features, we estimate the average of 8% false-positive and 1% false-negative errors.

The increase in the number of counterfeit and recycled microelectronic chips in recent years has created significant security and safety concerns in various applications. Hence, detecting such counterfeit chips in electronic systems is critical before deployment in the field. Unfortunately, the conventional verification tools using physical inspection and side-channel methods are costly, unscalable, error-prone, and often incompatible with legacy systems. This paper introduces a generic non-invasive and low-cost counterfeit chip detection based on characterizing the impedance of the system's power delivery network (PDN). Our method relies on the fact that the impedance of the counterfeit and recycled chips differs from the genuine ones. To sense such impedance variations confidently, we deploy scattering parameters, frequently used for impedance characterization of RF/microwave circuits. Our proposed approach can directly be applied to soldered chips on the system's PCB and does not require any modifications on the legacy systems. To validate our claims, we perform extensive measurements on genuine and aged samples from two families of STMicroelectronics chips to assess the effectiveness of the proposed approach.

Carbon dioxide storage is one of the main long-term strategies for reducing carbon dioxide emissions in the atmosphere. A clear example is Norway's Longship project. If these projects should succeed, the transport of huge volumes of carbon dioxide from the emissions source to the injection points may become a complex challenge. In this work, we propose the production of sodium-based organic carbonates that could be transported to storage sites and be reconverted to CO2. Solid carbonates can be transported in considerably lower volumes than gases or pressurized liquids. Sodium-based carbonates are insoluble in most of the organic solvents and will therefore precipitate in contrast to in aqueous solutions. Particularly, here we focus on sodium hydroxide-ethanol mixtures as solvents for precipitating sodium ethyl carbonate and sodium bicarbonate. Previous works on this approach used limited sodium hydroxide concentrations, which are insufficient to prove the effectiveness of the proposed process. In this paper, we studied higher sodium hydroxide concentrations in sodium hydroxide-ethanol mixtures than previously reported in the literature. To this end, we use the following strategy: (1) In-line monitoring of the formation of carbonates using an in-line FTIR; (2) In-line measurements of the weight increase, which correspond directly to the captured carbon dioxide and reveal the absorption capacity; (3) Characterization of the solids with X-ray diffraction and scanning electron microscope. Our FTIR results confirmed that both sodium ethyl carbonate and sodium bicarbonate were formed, which agrees with X-ray diffraction and scanning electron microscope. With this reactor design, the absorption capacities reached approximately 80–93% of the theoretical values (4.8–13.3 g/L respectively). We hypothesize that full conversion is hampered because the gas might take preferential paths due to gel formation during the experiments.

Cell metabolism is characterised by the highly coordinated conversion of nutrients into energy and biomass. In solid cancers, hypoxia, nutrient deficiencies, and tumour vasculature are incompatible with accelerated anabolic growth and require a rewiring of cancer cell metabolism. Driver gene mutations direct malignant cells away from oxidation to maximise energy production and biosynthesis while tumour-secreted factors degrade peripheral tissues to fuel disease progression and initiate metastasis. As it is vital to understand cancer cell metabolism and survival mechanisms, this review discusses the metabolic switch and current drug targets and clinical trials. In the future, metabolic markers may be included when phenotyping individual tumours to improve the therapeutic opportunities for personalised therapy.

As the core component of all organs, the extracellular matrix (ECM) is an interlocking macromolecular meshwork of proteins, glycoproteins, and proteoglycans that provides mechanical support to cells and tissues. In cancer, the ECM can be remodelled in response to environmental cues, and it controls a plethora of cellular functions, including metabolism, cell polarity, migration, and proliferation, to sustain and support oncogenesis. The biophysical and biochemical properties of the ECM, such as its structural arrangement and being a reservoir for bioactive molecules, control several intra- and intercellular signalling pathways and induce cytoskeletal changes that alter cell shapes, behaviour, and viability. Desmoplasia is a major component of solid tumours. The abnormal deposition and composition of the tumour matrix lead to biochemical and biomechanical alterations that determine disease development and resistance to treatment. This review summarises the complex roles of ECM in cancer and highlights the possible therapeutic targets and how to potentially remodel the dysregulated ECM in the future. Furthering our understanding of the ECM in cancer is important as the modification of the ECM will probably become an important tool in the characterisation of individual tumours and personalised treatment options.

Cell metabolism is characterised by the highly coordinated conversion of nutrients into energy and biomass. In solid cancers, hypoxia, nutrient deficiencies, and tumour vasculature are incompatible with accelerated anabolic growth and require a rewiring of cancer cell metabolism. Driver gene mutations direct malignant cells away from oxidation to maximise energy production and biosynthesis while tumour-secreted factors degrade peripheral tissues to fuel disease progression and initiate metastasis. As it is vital to understand cancer cell metabolism and survival mechanisms, this review discusses the metabolic switch and current drug targets and clinical trials. In the future, metabolic markers may be included when phenotyping individual tumours to improve the therapeutic opportunities for personalised therapy.

Background In colorectal cancer, the effects of immune checkpoint inhibitors are mostly limited to patients with deficient mismatch repair tumors, characterized by a high grade infiltration of CD8+T cells. Interventions aimed at increasing intratumoral CD8+T-cell infiltration in proficient mismatch repair tumors are lacking. Methods We conducted a proof of concept phase 1/2 clinical trial, where patients with non-metastasizing sigmoid or rectal cancer, scheduled for curative intended surgery, were treated with an endoscopic intratumorally administered neoadjuvant influenza vaccine. Blood and tumor samples were collected before the injection and at the time of surgery. The primary outcome was safety of the intervention. Evaluation of pathological tumor regression grade, immunohistochemistry, flow cytometry of blood, tissue bulk transcriptional analyses, and spatial protein profiling of tumor regions were all secondary outcomes. Results A total of 10 patients were included in the trial. Median patient age was 70 years (range 54-78), with 30% women. All patients had proficient mismatch repair Union of International Cancer Control stage I-III tumors. No endoscopic safety events occurred, with all patients undergoing curative surgery as scheduled (median 9 days after intervention). Increased CD8+T-cell tumor infiltration was evident after vaccination (median 73 vs 315 cells/mm 2, p<0.05), along with significant downregulation of messenger RNA gene expression related to neutrophils and upregulation of transcripts encoding cytotoxic functions. Spatial protein analysis showed significant local upregulation of programmed death-ligand 1 (PD-L1) (adjusted p value<0.05) and downregulation of FOXP3 (adjusted p value<0.05). Conclusions Neoadjuvant intratumoral influenza vaccine treatment in this cohort was demonstrated to be safe and feasible, and to induce CD8+T-cell infiltration and upregulation of PD-L1 proficient mismatch repair sigmoid and rectal tumors. Definiti

The COVID-19 pandemic has forced many people to limit their social activities, which has resulted in a rise in mental illnesses, particularly depression. To diagnose these illnesses with accuracy and speed, and prevent severe outcomes such as suicide, the use of machine learning has become increasingly important. Additionally, to provide precise and understandable diagnoses for better treatment, AI scientists and researchers must develop interpretable AI-based solutions. This article provides an overview of relevant articles in the field of machine learning and interpretable AI, which helps to understand the advantages and disadvantages of using AI in psychiatry disorder detection applications., Comment: 12 pages

The threats of physical side-channel attacks and their countermeasures have been widely researched. Most physical side-channel attacks rely on the unavoidable influence of computation or storage on current consumption or voltage drop on a chip. Such data-dependent influence can be exploited by, for instance, power or electromagnetic analysis. In this work, we introduce a novel non-invasive physical side-channel attack, which exploits the data-dependent changes in the impedance of the chip. Our attack relies on the fact that the temporarily stored contents in registers alter the physical characteristics of the circuit, which results in changes in the die's impedance. To sense such impedance variations, we deploy a well-known RF/microwave method called scattering parameter analysis, in which we inject sine wave signals with high frequencies into the system's power distribution network (PDN) and measure the echo of the signals. We demonstrate that according to the content bits and physical location of a register, the reflected signal is modulated differently at various frequency points enabling the simultaneous and independent probing of individual registers. Such side-channel leakage challenges the $t$-probing security model assumption used in masking, which is a prominent side-channel countermeasure. To validate our claims, we mount non-profiled and profiled impedance analysis attacks on hardware implementations of unprotected and high-order masked AES. We show that in the case of the profiled attack, only a single trace is required to recover the secret key. Finally, we discuss how a specific class of hiding countermeasures might be effective against impedance leakage.

During the COVID-19 pandemic, European states have taken numerous measures to prevent the spread of the coronavirus. Several states have introduced various forms of compulsory vaccination against COVID-19. While vaccines are one of the most effective tools for protecting people against COVID-19, it raises the question to which extent states may justifiably make vaccination schemes compulsory in the pursuit of public health. This paper, therefore, analyses the compatibility between compulsory vaccination and the right to respect for private life as set out in Article 8 of the Convention for the Protection of Human Rights and Fundamental Freedoms (the ECHR). As of today, the European Court of Human Rights (the ECtHR) has not decided whether vaccine mandates are compatible with the right to respect for private life. An interference in the right to respect for private life must be in accordance with the law and fulfil one of the legitimate aims that are set out in Article 8.2 of the ECHR. An interference also needs to be necessary in a democratic society in order to achieve that legitimate aim. The protection of health as well as the protection of the rights and freedoms of others are two of the legitimate aims stipulated in Article 8 of the ECHR that are relevant in relation to the introduction of compulsory vaccination in society. In assessing whether an interference is necessary in a democratic society, the states enjoy a certain margin of appreciation. However, their assessment remains subject to review by the ECtHR. The principle of proportionality is an important part in assessing whether the interference has been necessary in a democratic society or not. The interference in question must remain proportionate to the legitimate aim pursued. In this paper, the compatibility between compulsory COVID-19 vaccination and the right to respect for private life is examined primarily by analysing prior case law of the ECtHR concerning vaccination and other medical interven

Objective: Immediate cartilage structural alterations in the acute phase after an anterior cruciate ligament (ACL) rupture may be a precursor to posttraumatic osteoarthritis (PTOA) development. Our aim was to describe changes in cartilage matrix in the subacute phase of the acutely ACL-injured knee compared to the contralateral uninjured knee. Design: Participants (n = 118) aged 15-40 years with an acute ACL injury were consecutively included in subacute phase after acute ACL-injury and underwent MRI (mean 29 days post trauma) of both knees. Mean T2 relaxation times, T2 spatial coefficient of variation and cartilage thickness were determined for different regions of the tibiofemoral cartilage. Differences between the acutely ACL-injured and uninjured knee were evaluated using Wilcoxon signed-rank test. Results: T2 relaxation time in injured knees was increased in multiple cartilage regions from both medial and lateral compartment compared to contralateral knees, mostly in medial trochlea and posterior tibia (P-value<0.001). In the same sites of injured knees, we observed significantly thinner cartilage. Moreover, injured knees presented shorter T2 relaxation time in superficial cartilage on lateral central femur and trochlea (P-value<0.001), and decreased T2 spatial coefficient of variation in lateral trochlea and load bearing regions of medial-central femoral condyle and central tibia in both compartments. Conclusion: Small but statistically significant differences were observed in the subacute phase between ACL-injured and uninjured knee in cartilage T2 relaxation time and cartilage thickness. Future longitudinal observations of the same cohort will allow for better understanding of early development of PTOA. (C) 2022 The Author(s). Published by Elsevier Ltd on behalf of Osteoarthritis Research Society International., Funding Agencies|Swedish Research Council; Swedish Research Council for Sport Science; Medical Research Council of Southeast; Jane & Aatos Erkko Foundation; ALF Grants Region Ostergotland; ALF Grants Region Skane

Objective: Immediate cartilage structural alterations in the acute phase after an anterior cruciate ligament (ACL) rupture may be a precursor to posttraumatic osteoarthritis (PTOA) development. Our aim was to describe changes in cartilage matrix in the subacute phase of the acutely ACL-injured knee compared to the contralateral uninjured knee. Design: Participants (n = 118) aged 15-40 years with an acute ACL injury were consecutively included in subacute phase after acute ACL-injury and underwent MRI (mean 29 days post trauma) of both knees. Mean T2 relaxation times, T2 spatial coefficient of variation and cartilage thickness were determined for different regions of the tibiofemoral cartilage. Differences between the acutely ACL-injured and uninjured knee were evaluated using Wilcoxon signed-rank test. Results: T2 relaxation time in injured knees was increased in multiple cartilage regions from both medial and lateral compartment compared to contralateral knees, mostly in medial trochlea and posterior tibia (P-value<0.001). In the same sites of injured knees, we observed significantly thinner cartilage. Moreover, injured knees presented shorter T2 relaxation time in superficial cartilage on lateral central femur and trochlea (P-value<0.001), and decreased T2 spatial coefficient of variation in lateral trochlea and load bearing regions of medial-central femoral condyle and central tibia in both compartments. Conclusion: Small but statistically significant differences were observed in the subacute phase between ACL-injured and uninjured knee in cartilage T2 relaxation time and cartilage thickness. Future longitudinal observations of the same cohort will allow for better understanding of early development of PTOA. (C) 2022 The Author(s). Published by Elsevier Ltd on behalf of Osteoarthritis Research Society International., Funding Agencies|Swedish Research Council; Swedish Research Council for Sport Science; Medical Research Council of Southeast; Jane & Aatos Erkko Foundation; ALF Grants Region Ostergotland; ALF Grants Region Skane

The use of automated procedures has recently become popular in the causal inference literature. Naive implementations of automatic procedures stand in contrast to the perspective advocated in Imbens and Rubin's Causal Inference. Imbens and Rubin suggest that researchers should make modelling decisions informed by subjective knowledge. We make use of simulated data to compare Imbens and Rubin's approach to naive implementations of two automatic procedures: Genetic Matching and Entropy Balancing. In addition we perform a small Monte Carlo simulation, based on one of the simulated data sets. Using the simulated data sets and the Monte Carlo simulations, we illustrate and explore benefits and drawbacks of the different approaches. We argue that there are benefits to make use of design-decisions grounded in subjective knowledge.

The heritagisation of food reveals the underlying processes by which various actors articulate a particular foodstuff as a heritage in an attempt at pursuing differing aims. Food heritage evokes images, memories, and pride, or motivates habitual consumption, and it can become a lifestyle or even a source of income. Seafood has been reconceptualized as a heritage cuisine in Qeshm Island, Iran. This qualitative case study seeks to explore how the process of food heritagization is carried out by local and external actors in this region. Drawing on the interpretivist paradigm, data was gathered through in-depth semi-structured interviews, and document analysis of literature reviews, books, magazines, and news. Inspired by the theory of food heritagization by Bessiere (2013), data was analyzed through thematic analysis. Findings demonstrated that that place attachment greatly influenced the motivations and aspirations of local community for the participation in the heritagization of local food and also development of tourism development. The reported findings are expected to contribute to the literature on food culture, specifically heritage food.

Objective: Immediate cartilage structural alterations in the acute phase after an anterior cruciate ligament (ACL) rupture may be a precursor to posttraumatic osteoarthritis (PTOA) development. Our aim was to describe changes in cartilage matrix in the subacute phase of the acutely ACL-injured knee compared to the contralateral uninjured knee. Design: Participants (n = 118) aged 15–40 years with an acute ACL injury were consecutively included in subacute phase after acute ACL-injury and underwent MRI (mean 29 days post trauma) of both knees. Mean T2 relaxation times, T2 spatial coefficient of variation and cartilage thickness were determined for different regions of the tibiofemoral cartilage. Differences between the acutely ACL-injured and uninjured knee were evaluated using Wilcoxon signed-rank test. Results: T2 relaxation time in injured knees was increased in multiple cartilage regions from both medial and lateral compartment compared to contralateral knees, mostly in medial trochlea and posterior tibia (P-value<0.001). In the same sites of injured knees, we observed significantly thinner cartilage. Moreover, injured knees presented shorter T2 relaxation time in superficial cartilage on lateral central femur and trochlea (P-value<0.001), and decreased T2 spatial coefficient of variation in lateral trochlea and load bearing regions of medial-central femoral condyle and central tibia in both compartments. Conclusions: Small but statistically significant differences were observed in the subacute phase between ACL-injured and uninjured knee in cartilage T2 relaxation time and cartilage thickness. Future longitudinal observations of the same cohort will allow for better understanding of early development of PTOA.

Objective: Immediate cartilage structural alterations in the acute phase after an anterior cruciate ligament (ACL) rupture may be a precursor to posttraumatic osteoarthritis (PTOA) development. Our aim was to describe changes in cartilage matrix in the subacute phase of the acutely ACL-injured knee compared to the contralateral uninjured knee. Design: Participants (n = 118) aged 15-40 years with an acute ACL injury were consecutively included in subacute phase after acute ACL-injury and underwent MRI (mean 29 days post trauma) of both knees. Mean T2 relaxation times, T2 spatial coefficient of variation and cartilage thickness were determined for different regions of the tibiofemoral cartilage. Differences between the acutely ACL-injured and uninjured knee were evaluated using Wilcoxon signed-rank test. Results: T2 relaxation time in injured knees was increased in multiple cartilage regions from both medial and lateral compartment compared to contralateral knees, mostly in medial trochlea and posterior tibia (P-value<0.001). In the same sites of injured knees, we observed significantly thinner cartilage. Moreover, injured knees presented shorter T2 relaxation time in superficial cartilage on lateral central femur and trochlea (P-value<0.001), and decreased T2 spatial coefficient of variation in lateral trochlea and load bearing regions of medial-central femoral condyle and central tibia in both compartments. Conclusion: Small but statistically significant differences were observed in the subacute phase between ACL-injured and uninjured knee in cartilage T2 relaxation time and cartilage thickness. Future longitudinal observations of the same cohort will allow for better understanding of early development of PTOA. (C) 2022 The Author(s). Published by Elsevier Ltd on behalf of Osteoarthritis Research Society International., Funding Agencies|Swedish Research Council; Swedish Research Council for Sport Science; Medical Research Council of Southeast; Jane & Aatos Erkko Foundation; ALF Grants Region Ostergotland; ALF Grants Region Skane

During the COVID-19 pandemic, European states have taken numerous measures to prevent the spread of the coronavirus. Several states have introduced various forms of compulsory vaccination against COVID-19. While vaccines are one of the most effective tools for protecting people against COVID-19, it raises the question to which extent states may justifiably make vaccination schemes compulsory in the pursuit of public health. This paper, therefore, analyses the compatibility between compulsory vaccination and the right to respect for private life as set out in Article 8 of the Convention for the Protection of Human Rights and Fundamental Freedoms (the ECHR). As of today, the European Court of Human Rights (the ECtHR) has not decided whether vaccine mandates are compatible with the right to respect for private life. An interference in the right to respect for private life must be in accordance with the law and fulfil one of the legitimate aims that are set out in Article 8.2 of the ECHR. An interference also needs to be necessary in a democratic society in order to achieve that legitimate aim. The protection of health as well as the protection of the rights and freedoms of others are two of the legitimate aims stipulated in Article 8 of the ECHR that are relevant in relation to the introduction of compulsory vaccination in society. In assessing whether an interference is necessary in a democratic society, the states enjoy a certain margin of appreciation. However, their assessment remains subject to review by the ECtHR. The principle of proportionality is an important part in assessing whether the interference has been necessary in a democratic society or not. The interference in question must remain proportionate to the legitimate aim pursued. In this paper, the compatibility between compulsory COVID-19 vaccination and the right to respect for private life is examined primarily by analysing prior case law of the ECtHR concerning vaccination and other medical interven

The heritagisation of food reveals the underlying processes by which various actors articulate a particular foodstuff as a heritage in an attempt at pursuing differing aims. Food heritage evokes images, memories, and pride, or motivates habitual consumption, and it can become a lifestyle or even a source of income. Seafood has been reconceptualized as a heritage cuisine in Qeshm Island, Iran. This qualitative case study seeks to explore how the process of food heritagization is carried out by local and external actors in this region. Drawing on the interpretivist paradigm, data was gathered through in-depth semi-structured interviews, and document analysis of literature reviews, books, magazines, and news. Inspired by the theory of food heritagization by Bessiere (2013), data was analyzed through thematic analysis. Findings demonstrated that that place attachment greatly influenced the motivations and aspirations of local community for the participation in the heritagization of local food and also development of tourism development. The reported findings are expected to contribute to the literature on food culture, specifically heritage food.

The ability to manipulate clouds of ultra-cold atoms is crucial for modern experiments on quantum manybody systems and quantum thermodynamics as well as future metrological applications of Bose-Einstein condensate. While optical manipulation offers almost arbitrary flexibility, the precise control of the resulting dipole potentials and the mitigation of unwanted disturbances is quite involved and only heuristic algorithms with rather slow convergence rates are available up to now. This paper thus suggests the application of iterative learning control (ILC) methods to generate fine-tuned effective potentials in the presence of uncertainties and external disturbances. Therefore, the given problem is reformulated to obtain a one-dimensional tracking problem by using a quasicontinuous input mapping which can be treated by established ILC methods. Finally, the performance of the proposed concept is illustrated in a simulation scenario., Comment: To appear in Proceedings of the 61st IEEE Conference on Decision and Control (CDC)

Objective: Immediate cartilage structural alterations in the acute phase after an anterior cruciate ligament (ACL) rupture may be a precursor to posttraumatic osteoarthritis (PTOA) development. Our aim was to describe changes in cartilage matrix in the subacute phase of the acutely ACL-injured knee compared to the contralateral uninjured knee. Design: Participants (n = 118) aged 15-40 years with an acute ACL injury were consecutively included in subacute phase after acute ACL-injury and underwent MRI (mean 29 days post trauma) of both knees. Mean T2 relaxation times, T2 spatial coefficient of variation and cartilage thickness were determined for different regions of the tibiofemoral cartilage. Differences between the acutely ACL-injured and uninjured knee were evaluated using Wilcoxon signed-rank test. Results: T2 relaxation time in injured knees was increased in multiple cartilage regions from both medial and lateral compartment compared to contralateral knees, mostly in medial trochlea and posterior tibia (P-value<0.001). In the same sites of injured knees, we observed significantly thinner cartilage. Moreover, injured knees presented shorter T2 relaxation time in superficial cartilage on lateral central femur and trochlea (P-value<0.001), and decreased T2 spatial coefficient of variation in lateral trochlea and load bearing regions of medial-central femoral condyle and central tibia in both compartments. Conclusion: Small but statistically significant differences were observed in the subacute phase between ACL-injured and uninjured knee in cartilage T2 relaxation time and cartilage thickness. Future longitudinal observations of the same cohort will allow for better understanding of early development of PTOA. (C) 2022 The Author(s). Published by Elsevier Ltd on behalf of Osteoarthritis Research Society International., Funding Agencies|Swedish Research Council; Swedish Research Council for Sport Science; Medical Research Council of Southeast; Jane & Aatos Erkko Foundation; ALF Grants Region Ostergotland; ALF Grants Region Skane

Objective: Immediate cartilage structural alterations in the acute phase after an anterior cruciate ligament (ACL) rupture may be a precursor to posttraumatic osteoarthritis (PTOA) development. Our aim was to describe changes in cartilage matrix in the subacute phase of the acutely ACL-injured knee compared to the contralateral uninjured knee. Design: Participants (n = 118) aged 15-40 years with an acute ACL injury were consecutively included in subacute phase after acute ACL-injury and underwent MRI (mean 29 days post trauma) of both knees. Mean T2 relaxation times, T2 spatial coefficient of variation and cartilage thickness were determined for different regions of the tibiofemoral cartilage. Differences between the acutely ACL-injured and uninjured knee were evaluated using Wilcoxon signed-rank test. Results: T2 relaxation time in injured knees was increased in multiple cartilage regions from both medial and lateral compartment compared to contralateral knees, mostly in medial trochlea and posterior tibia (P-value<0.001). In the same sites of injured knees, we observed significantly thinner cartilage. Moreover, injured knees presented shorter T2 relaxation time in superficial cartilage on lateral central femur and trochlea (P-value<0.001), and decreased T2 spatial coefficient of variation in lateral trochlea and load bearing regions of medial-central femoral condyle and central tibia in both compartments. Conclusion: Small but statistically significant differences were observed in the subacute phase between ACL-injured and uninjured knee in cartilage T2 relaxation time and cartilage thickness. Future longitudinal observations of the same cohort will allow for better understanding of early development of PTOA. (C) 2022 The Author(s). Published by Elsevier Ltd on behalf of Osteoarthritis Research Society International., Funding Agencies|Swedish Research Council; Swedish Research Council for Sport Science; Medical Research Council of Southeast; Jane & Aatos Erkko Foundation; ALF Grants Region Ostergotland; ALF Grants Region Skane

Artificial intelligence (AI) and machine learning (ML) techniques have been increasingly used in several fields to improve performance and the level of automation. In recent years, this use has exponentially increased due to the advancement of high-performance computing and the ever increasing size of data. One of such fields is that of hardware design; specifically the design of digital and analog integrated circuits~(ICs), where AI/ ML techniques have been extensively used to address ever-increasing design complexity, aggressive time-to-market, and the growing number of ubiquitous interconnected devices (IoT). However, the security concerns and issues related to IC design have been highly overlooked. In this paper, we summarize the state-of-the-art in AL/ML for circuit design/optimization, security and engineering challenges, research in security-aware CAD/EDA, and future research directions and needs for using AI/ML for security-aware circuit design.

One of the critical challenges in infrastructural constructions is designing and planning operations and their related resources. The complex interlinked composition of different factors and variables affecting resource productivity has made simulation a powerful approach for operational planning. The construction sector has recently seen a notable surge in applying various simulation tools to enhance further the quality of projects planning, particularly in large-scale infrastructure developments (e.g., highway construction). Due to possible cost overruns in improper resource allocation, optimizing the design and construction planning stages of megaprojects such as massive pavement projects is essential. Recent studies aimed to build a simulation-based strategy in construction designing and planning by combining various simulation approaches (e.g., discrete-event simulation, system dynamics, agent-based simulation, and hybrid simulation) to enhance the planning phase. This paper introduces an evolving real-time hybrid simulation technique regarding the projects intrinsic time-varying inputs and factors to optimize the planning of Roller Compacted Concrete (RCC) pavement projects. Several scenarios are investigated using various resource combinations to achieve the best execution method for delivering concrete to the project. An actual highway project case study validates the proposed model and its application for future projects. This studys findings exhibit the proficiencies of the simulation-based approach in resource planning of RCC pavement projects within the time and cost constraints and their related regulations.

The use of automated procedures has recently become popular in the causal inference literature. Naive implementations of automatic procedures stand in contrast to the perspective advocated in Imbens and Rubin's Causal Inference. Imbens and Rubin suggest that researchers should make modelling decisions informed by subjective knowledge. We make use of simulated data to compare Imbens and Rubin's approach to naive implementations of two automatic procedures: Genetic Matching and Entropy Balancing. In addition we perform a small Monte Carlo simulation, based on one of the simulated data sets. Using the simulated data sets and the Monte Carlo simulations, we illustrate and explore benefits and drawbacks of the different approaches. We argue that there are benefits to make use of design-decisions grounded in subjective knowledge.

Copyright © 2019 ASME. Pulsating flame jets have been widely used in open-top carbon anode baking furnaces for aluminum electrolysis. Reducing energy consumption and pollutant emissions are still major challenges in baking (heat-treatment) carbon anode blocks. It is also of immense significance to bake all the anodes uniformly irrespective of their position in the furnace. Baking homogeneity can be enhanced noticeably by optimizing anode baking operational, geometrical, and physical parameters. In the present study, CFD simulations are combined with a response surface methodology to investigate and optimize the effects of pulse pressure, pulse frequency, and mainstream inlet oxygen concentration and mainstream inlet temperature. Two-levels half fractional factorial design with a center point is employed. It is perceived that pulse combustion with short pulse time and high momentum results in significant enhancement of the anode baking furnace energy efficiency. The temperature homogeneity is also significantly improved. It is found that the oxygen concentration is statistically the most significant parameter on NOx and soot formations, followed by the fuel flow rate. For NOx formation, air inlet oxygen concentration has a strong interaction with pulse duration. Coupling CFD models with the response surface methodologies demonstrated great potential in multi-objective optimization of the anode baking process with enhanced energy efficiency and baking uniformity.

Copyright © 2018 ASME. The cost and quality of aluminum produced by the reduction process are strongly dependent on heat treated (baked) carbon anodes. A typical aluminum smelter requires more than half a million tons of carbon anodes for producing one million ton of aluminum. The anode baking process is very energy intensive, approximately requires 2GJ of energy per ton of carbon anodes. Moreover, pollutant emissions such as NOx and soot formation are of major concern in the aluminum anode baking furnace. The current study aims at developing an accurate numerical platform for predicting the combustion and emissions characteristics of an anode baking furnace. The Brookes and Moss model, and the extended Zeldovich mechanism are employed to estimate soot and NOx concentration, respectively. Considering a fire group of three burner bridges, one after the other in the fire direction, combustion and emissions features of these three firing sections are interrelated in terms of oxidizer’s concentration and temperature. In the present study, considering this interconnection, the effect of diluted oxygen concentration at elevated oxidizer’s temperature (~1200°C), which are the key features of the moderate or intense low oxygen dilution (MILD) combustion are analyzed. It is observed that by circulating some of the exhaust gases through the ABF crossovers, oxygen dilution occurs which results in higher fuel efficiency, lower pollutant emissions, and more homogeneous flow and temperature fields.

В статье приведена актуальность одежды народов Азии с декоративными элементами в стиле попурри. Рекомендуемые элементы в одежде народов Азии и их места предназначения, а также рекомендуемая цветовая палитра и геометрическая тематика. Использование видов вышивок, тканей спринтами растительной, цветочной тематикой.

В статье приведена актуальность одежды народов Азии с декоративными элементами в стиле попурри. Рекомендуемые элементы в одежде народов Азии и их места предназначения, а также рекомендуемая цветовая палитра и геометрическая тематика. Использование видов вышивок, тканей спринтами растительной, цветочной тематикой.

STUDY QUESTION: Can we identify patient characteristics that distinguish which ovulatory infertile women undergoing hysterosalpingography (HSG) benefit more or less from flushing with oil-based contrast medium compared to water-based contrast medium? SUMMARY ANSWER: In ovulatory infertile women, HSG with oil-based contrast medium resulted in higher 6-month ongoing pregnancy and live birth rates as compared to HSG with water-based contrast medium and this treatment effect was independent of characteristics of the couple. WHAT IS KNOWN ALREADY: We recently showed that in infertile women undergoing HSG, flushing with oil-based contrast medium resulted in more ongoing pregnancies than flushing with water-based contrast medium. STUDY DESIGN, SIZE, DURATION: We used data from our randomized clinical trial (RCT) in which 1,119 ovulatory infertile women undergoing HSG during fertility work-up were randomized for use of oil-based (N = 557) or water-based (N = 562) contrast medium. PARTICIPANTS/MATERIALS, SETTING, METHODS: We built logistic regression models to predict ongoing pregnancy and live birth (secondary outcome) as a function of the specific contrast, the specific marker, and marker-by-contrast-interaction. Markers considered were female age, maternal ethnicity, female smoking, body mass index (BMI), duration of infertility, infertility being primary or secondary, sperm quality, and previous appendectomy. MAIN RESULTS AND THE ROLE OF CHANCE: The 6-month ongoing pregnancy rates in the overall population were 39.7% after use of oil-based contrast versus 29.1% after use of water-based contrast medium [relative risk (RR), 1.37; 95% confidence interval (CI), 1.16-1.61; P < 0.001]. Among the studied baseline characteristics, BMI (P = 0.002) and semen volume (P = 0.02) were statistically significant prognosticators. The treatment effect of oil-based contrast was stronger in women with a BMI <=30 kg/m2 [RR, 1.54; 95% CI, 1.23-1.92; P = 0.002], and in women whose partner had

STUDY QUESTION: Can we identify patient characteristics that distinguish which ovulatory infertile women undergoing hysterosalpingography (HSG) benefit more or less from flushing with oil-based contrast medium compared to water-based contrast medium? SUMMARY ANSWER: In ovulatory infertile women, HSG with oil-based contrast medium resulted in higher 6-month ongoing pregnancy and live birth rates as compared to HSG with water-based contrast medium and this treatment effect was independent of characteristics of the couple. WHAT IS KNOWN ALREADY: We recently showed that in infertile women undergoing HSG, flushing with oil-based contrast medium resulted in more ongoing pregnancies than flushing with water-based contrast medium. STUDY DESIGN, SIZE, DURATION: We used data from our randomized clinical trial (RCT) in which 1,119 ovulatory infertile women undergoing HSG during fertility work-up were randomized for use of oil-based (N = 557) or water-based (N = 562) contrast medium. PARTICIPANTS/MATERIALS, SETTING, METHODS: We built logistic regression models to predict ongoing pregnancy and live birth (secondary outcome) as a function of the specific contrast, the specific marker, and marker-by-contrast-interaction. Markers considered were female age, maternal ethnicity, female smoking, body mass index (BMI), duration of infertility, infertility being primary or secondary, sperm quality, and previous appendectomy. MAIN RESULTS AND THE ROLE OF CHANCE: The 6-month ongoing pregnancy rates in the overall population were 39.7% after use of oil-based contrast versus 29.1% after use of water-based contrast medium [relative risk (RR), 1.37; 95% confidence interval (CI), 1.16-1.61; P < 0.001]. Among the studied baseline characteristics, BMI (P = 0.002) and semen volume (P = 0.02) were statistically significant prognosticators. The treatment effect of oil-based contrast was stronger in women with a BMI <=30 kg/m2 [RR, 1.54; 95% CI, 1.23-1.92; P = 0.002], and in women whose partner had