The impact of stroke and bleeding on mortality and quality of life during the first year after TAVI: A POPular TAVI subanalysis.

BACKGROUND: Bleeding and stroke are frequent complications after transcatheter aortic valve implantation (TAVI). The mortality risk associated with these events has been reported before, but data regarding their impact on health-related quality of life (QoL) is limited. AIM: To evaluate the impact of bleeding and stroke occurring within 30 days after TAVI, on mortality and QoL during the first year after TAVI. METHODS: POPular TAVI was a randomized clinical trial that evaluated the addition of clopidogrel to aspirin or oral anticoagulation in patients undergoing TAVI. Besides clinical outcomes, QoL was assessed using the Short Form-12 and EuroQoL Five Dimensions questionnaires before, and at 3, 6, and 12 months after TAVI. RESULTS: Major or life-threatening bleeding occurred in 81 patients (8.3%) and was associated with an increased risk of death (hazard ratio [HR] 1.95 [95% confidence interval (CI) 1.00-3.79]); minor bleeding occurred in 104 patients (10.6%) and was not associated with mortality (HR 0.75 [95% CI 0.30-1.89]). Stroke occurred in 35 patients (3.6%) and was associated with an increased risk of death (HR 2.90 [95% CI 1.23-6.83]). Mean mental component summary (MCS-12) scores over time were lower in patients with major or life-threatening bleeding (p = 0.01), and similar in patients with minor bleeding, compared to patients without bleeding; mean physical component summary (PCS-12) scores, EQ-5D index, and visual analog scale (VAS) were similar between those patients. Mean MCS-12 scores were lower in patients with stroke (p = 0.01), mean PCS-12, EQ-5D index, and VAS were similar compared to patients without stroke. CONCLUSION: Major or life-threatening bleeding and stroke were associated with an increased risk of death and decreased mental QoL in the first year after TAVI.

Modeling fisheries and carbon sequestration ecosystem services under deep uncertainty in the ocean twilight zone.

Mesopelagic fishes are a vital component of the biological carbon pump and are, to date, largely unexploited. In recent years, there has been an increased interest in harvesting the mesopelagic zone to produce fish feed for aquaculture. However, great uncertainties exist in how the mesopelagic zone interacts with the climate and food webs, presenting a dilemma for policy. Here, we investigate the consequences of potential policies relating to mesopelagic harvest quotas with a dynamic social-ecological modeling approach, combining system dynamics and global sensitivity analyses informed by participatory modeling. Our analyses reveal that, in simulations of mesopelagic fishing scenarios, uncertainties about mesopelagic fish population dynamics have the most pronounced influence on potential outcomes. The analysis also shows that prioritizing the development of the fishing industry over environmental protection would lead to a significantly higher social cost of climate change to society. Given the large uncertainties and the potential large impacts on oceanic carbon sequestration, a precautionary approach to developing mesopelagic fisheries is warranted.

Continuation versus Interruption of Oral Anticoagulation during TAVI.

BACKGROUND: One third of patients undergoing transcatheter aortic-valve implantation (TAVI) have an indication for oral anticoagulation owing to concomitant diseases. Interruption of oral anticoagulation during TAVI may decrease the risk of bleeding, whereas continuation may decrease the risk of thromboembolism. METHODS: We conducted an international, open-label, randomized, noninferiority trial involving patients who were receiving oral anticoagulants and were planning to undergo TAVI. Patients were randomly assigned in a 1:1 ratio to periprocedural continuation or interruption of oral anticoagulation. The primary outcome was a composite of death from cardiovascular causes, stroke from any cause, myocardial infarction, major vascular complications, or major bleeding within 30 days after TAVI. RESULTS: A total of 858 patients were included in the modified intention-to-treat population: 431 were assigned to continuation and 427 to interruption of oral anticoagulation. A primary-outcome event occurred in 71 patients (16.5%) in the continuation group and in 63 (14.8%) in the interruption group (risk difference, 1.7 percentage points; 95% confidence interval [CI], -3.1 to 6.6; P = 0.18 for noninferiority). Thromboembolic events occurred in 38 patients (8.8%) in the continuation group and in 35 (8.2%) in the interruption group (risk difference, 0.6 percentage points; 95% CI, -3.1 to 4.4). Bleeding occurred in 134 patients (31.1%) in the continuation group and in 91 (21.3%) in the interruption group (risk difference, 9.8 percentage points; 95% CI, 3.9 to 15.6). CONCLUSIONS: In patients undergoing TAVI with a concomitant indication for oral anticoagulation, periprocedural continuation was not noninferior to interruption of oral anticoagulation during TAVI with respect to the incidence of a composite of death from cardiovascular causes, stroke, myocardial infarction, major vascular complications, or major bleeding at 30 days. (Funded by the Netherlands Organization for Health Research and Development and the St. Antonius Research Fund; POPular PAUSE TAVI ClinicalTrials.gov number, NCT04437303.).

Strongly Inhibited Spontaneous Emission of PbS Quantum Dots Covalently Bound to 3D Silicon Photonic Band Gap Crystals.

We present an optical study of the spontaneous emission of lead sulfide (PbS) nanocrystal quantum dots in 3D photonic band gap crystals made from silicon. The nanocrystals emit in the near-infrared range to be compatible with 3D silicon nanophotonics. The nanocrystals are covalently bound to polymer brush layers that are grafted from the Si-air interfaces inside the nanostructure by using surface-initiated atom transfer radical polymerization. The presence and position of the quantum dots were previously characterized by synchrotron X-ray fluorescence tomography. We report both continuous wave emission spectra and time-resolved, time-correlated single photon counting. In time-resolved measurements, we observe that the total emission rate greatly increases when the quantum dots are transferred from suspension to the silicon nanostructures, likely due to quenching (or increased nonradiative decay) that is tentatively attributed to the presence of Cu catalysts during the synthesis. In this regime, continuous wave emission spectra are known to be proportional to the radiative rate and thus to the local density of states. In spectra normalized to those taken on flat silicon outside the crystals, we observe a broad and deep stop band that we attribute to a 3D photonic band gap with a relative bandwidth of up to 26%. The shapes of the relative emission spectra match well with the theoretical density of states spectra calculated with plane-wave expansion. The observed inhibition is 4-30 times, similar to previously reported record inhibitions, yet for coincidental reasons. Our results are relevant to applications in photochemistry, sensing, photovoltaics, and efficient miniature light sources.

HIV immunological non-responders are characterized by extensive immunosenescence and impaired lymphocyte cytokine production capacity.

Introduction: Immunological non-responders (INR) are people living with HIV (PLHIV) who fail to fully restore CD4+ T-cell counts despite complete viral suppression with antiretroviral therapy (ART). INR are at higher risk for non-HIV related morbidity and mortality. Previous research suggest persistent qualitative defects. Methods: The 2000HIV study (clinical trials NTC03994835) enrolled 1895 PLHIV, divided in a discovery and validation cohort. PLHIV with CD4 T-cell count <350 cells/mm3 after ≥2 years of suppressive ART were defined as INR and were compared to immunological responders (IR) with CD4 T-cell count >500 cells/mm3. Logistic and rank based regression were used to analyze clinical data, extensive innate and adaptive immunophenotyping, and ex vivo monocyte and lymphocyte cytokine production after stimulation with various stimuli. Results: The discovery cohort consisted of 62 INR and 1224 IR, the validation cohort of 26 INR and 243 IR. INR were older, had more advanced HIV disease before starting ART and had more frequently a history of non-AIDS related malignancy. INR had lower absolute CD4+ T-cell numbers in all subsets. Activated (HLA-DR+, CD38+) and exhausted (PD1+) subpopulations were proportionally increased in CD4 T-cells. Monocyte and granulocyte immunophenotypes were comparable. INR lymphocytes produced less IL-22, IFN-γ, IL-10 and IL-17 to stimuli. In contrast, monocyte cytokine production did not differ. The proportions of CD4+CD38+HLA-DR+ and CD4+PD1+ subpopulations showed an inversed correlation to lymphocyte cytokine production. Conclusions: INR compared to IR have hyperactivated and exhausted CD4+ T-cells in combination with lymphocyte functional impairment, while innate immune responses were comparable. Our data provide a rationale to consider the use of anti-PD1 therapy in INR.

The pursuit for markers of disease progression in behavioral variant frontotemporal dementia: a scoping review to optimize outcome measures for clinical trials.

Behavioral variant frontotemporal dementia (bvFTD) is a neurodegenerative disorder characterized by diverse and prominent changes in behavior and personality. One of the greatest challenges in bvFTD is to capture, measure and predict its disease progression, due to clinical, pathological and genetic heterogeneity. Availability of reliable outcome measures is pivotal for future clinical trials and disease monitoring. Detection of change should be objective, clinically meaningful and easily assessed, preferably associated with a biological process. The purpose of this scoping review is to examine the status of longitudinal studies in bvFTD, evaluate current assessment tools and propose potential progression markers. A systematic literature search (in PubMed and Embase.com) was performed. Literature on disease trajectories and longitudinal validity of frequently-used measures was organized in five domains: global functioning, behavior, (social) cognition, neuroimaging and fluid biomarkers. Evaluating current longitudinal data, we propose an adaptive battery, combining a set of sensitive clinical, neuroimaging and fluid markers, adjusted for genetic and sporadic variants, for adequate detection of disease progression in bvFTD.

Lead-based paint detection using perovskite fluorescence and X-ray fluorescence.

BACKGROUND: Ingestion of flakes of Pb-based paint by infants remains a global health hazard with life-long consequences. Pb-based paint was banned for residential use in the US and Western Europe decades ago but is still sold in many countries. This study evaluates the performance of a new kit for detecting exposed Pb-based paint relying on the formation of Pb-halide perovskite that fluoresces bright green under a UV flashlight after spraying a non-toxic reagent. RESULTS: Tests with the Lumetallix kit were conducted in parallel with X-fluorescence and inductively-coupled plasma atomic emission analysis upon acid digestion using paint currently sold in Côte d'Ivoire and samples of older US paint. Comparison of the three different methods indicates a detection limit for the Lumetallix kit of approximately 500 mg kg-1 (ppm) Pb in paint, with a sensitivity of 95 % and selectivity of 94 % relative to that threshold (n = 76). This detection limit is an order of magnitude below the US definition of Pb-based paint of 0.5 % (5,000 ppm) Pb by weight. SIGNIFICANCE: Because the kit is easy to use, exposed paint posing a risk could reliably be screened at scale by the general public. Any follow-up for confirmation and mitigation based on XRF measurements will need to consider that Pb-based paint covered with low-Pb paint will not respond to the kit but will be detected by XRF through the overpainted layer.

Cardiometabolic Differences in People Living with HIV Receiving Integrase Strand Transfer Inhibitors Compared to Non-nucleoside Reverse Transcriptase Inhibitors: Implications for Current ART Strategies.

In people living with HIV (PLHIV), integrase strand transfer inhibitors (INSTIs) are part of the first-line combination antiretroviral therapy (cART), while non-nucleoside reverse transcriptase inhibitor (NNRTI)-based regimens are alternatives. Distinct cART regimens may variably influence the risk for non-AIDS comorbidities. We aimed to compare the metabolome and lipidome of INSTI and NNRTI-based regimens. The 2000HIV study includes asymptomatic PLHIV (n = 1646) on long-term cART, separated into a discovery cohort with 730 INSTI and 617 NNRTI users, and a validation cohort encompassing 209 INSTI and 90 NNRTI users. Baseline plasma samples from INSTI and NNRTI users were compared using mass spectrometry-based untargeted metabolomic (n = 500) analysis. Perturbed metabolic pathways were identified using MetaboAnalyst software. Subsequently, nuclear magnetic resonance spectroscopy was used for targeted lipoprotein and lipid (n = 141) analysis. Metabolome homogeneity was observed between the different types of INSTI and NNRTI. In contrast, higher and lower levels of 59 and 45 metabolites, respectively, were found in the INSTI group compared to NNRTI users, of which 77.9% (81/104) had consistent directionality in the validation cohort. Annotated metabolites belonged mainly to 'lipid and lipid-like molecules', 'organic acids and derivatives' and 'organoheterocyclic compounds'. In pathway analysis, perturbed 'vitamin B1 (thiamin) metabolism', 'de novo fatty acid biosynthesis', 'bile acid biosynthesis' and 'pentose phosphate pathway' were detected, among others. Lipoprotein and lipid levels in NNRTIs were heterogeneous and could not be compared as a group. INSTIs compared to individual NNRTI types showed that HDL cholesterol was lower in INSTIs compared to nevirapine but higher in INSTIs compared to doravirine. In addition, LDL size was lower in INSTIs and nevirapine compared to doravirine. NNRTIs show more heterogeneous cardiometabolic effects than INSTIs, which hampers the comparison between these two classes of drugs. Targeted lipoproteomic and lipid NMR spectroscopy showed that INSTI use was associated with a more unfavorable lipid profile compared to nevirapine, which was shifted to a more favorable profile for INSTI when substituting nevirapine for doravirine, with evidently higher fold changes. The cardiovascular disease risk profile seems more favorable in INSTIs compared to NNRTIs in untargeted metabolomic analysis using mass-spectrometry.

Contributing to health system resilience during pandemics via purchasing and supply strategies: an exploratory system dynamics approach.

BACKGROUND: Health systems worldwide struggled to obtain sufficient personal protective equipment (PPE) and ventilators during the COVID-19 pandemic due to global supply chain disruptions. Our study's aim was to create a proof-of-concept model that would simulate the effects of supply strategies under various scenarios, to ultimately help decision-makers decide on alternative supply strategies for future similar health system related crises. METHODS: We developed a system dynamics model that linked a disease transmission model structure (susceptible, exposed, infectious, recovered (SEIR)) with a model for the availability of critical supplies in hospitals; thereby connecting care demand (patients' critical care in hospitals), with care supply (available critical equipment and supplies). To inform the model structure, we used data on critical decisions and events taking place surrounding purchase, supply, and availability of PPE and ventilators during the first phase of the COVID-19 pandemic within the English national health system. We used exploratory modelling and analysis to assess the effects of uncertainties on different supply strategies in the English health system under different scenarios. Strategies analysed were: (i) purchasing from the world market or (ii) through direct tender, (iii) stockpiling, (iv) domestic production, (v) supporting innovative supply strategies, or (vi) loaning ventilators from the private sector. RESULTS: We found through our exploratory analysis that a long-lasting shortage in PPE and ventilators is likely to be apparent in various scenarios. When considering the worst-case scenario, our proof-of-concept model shows that purchasing PPE and ventilators from the world market or through direct tender have the greatest influence on reducing supply shortages, compared to producing domestically or through supporting innovative supply strategies. However, these supply strategies are affected most by delays in their shipment time or set-up. CONCLUSION: We demonstrated that using a system dynamics and exploratory modelling approach can be helpful in identifying the purchasing and supply chain strategies that contribute to the preparedness and responsiveness of health systems during crises. Our results suggest that to improve health systems' resilience during pandemics or similar resource-constrained situations, purchasing and supply chain decision-makers can develop crisis frameworks that propose a plan of action and consequently accelerate and improve procurement processes and other governance processes during health-related crises; implement diverse supplier frameworks; and (re)consider stockpiling. This proof-of-concept model demonstrates the importance of including critical supply chain strategies as part of the preparedness and response activities to contribute to health system resilience.

Light-controlled morphological development of self-organizing bioinspired nanocomposites.

Nature's intricate biominerals inspire fundamental questions on self-organization and guide innovations towards functional materials. While advances in synthetic self-organization have enabled many levels of control, generating complex shapes remains difficult. Specifically, controlling morphologies during formation at the single micro/nanostructure level is the key challenge. Here, we steer the self-organization of barium carbonate nanocrystals and amorphous silica into complex nanocomposite morphologies by photogeneration of carbon dioxide (CO2) under ultraviolet (UV) light. Using modulations in the UV light intensity, we select the growth mode of the self-organization process inwards or outwards to form helical and coral-like morphologies respectively. The spatiotemporal control over CO2 photogeneration allows formation of different morphologies on pre-assigned locations, switching between different growth modes-to form for instance a coral on top of a helix or vice versa, and subtle sculpting and patterning of the nanocomposites during formation. These findings advance the understanding of these versatile self-organization processes and offer new prospects for tailored designs of functional materials using photochemically driven self-organization.

Postoperative Myocardial Injury and Inflammatory Biomarkers in Patients Undergoing Vascular Surgery: A Subanalysis of the Platelet Reactivity and Postoperative Myocardial Injury after Major Vascular Surgery (PROMISE) Study.

BACKGROUND: Postoperative myocardial injury (PMI) is associated with morbidity and mortality, but the aetiology remains unclear. We studied whether PMI is associated with perioperative systemic inflammation. The objective is the examination of the relationship between inflammatory biomarkers (Interleukin 6[IL-6], C-reactive protein [CRP]) and PMI, detected by elevated cardiac troponin (cTn), in patients undergoing elective open abdominal aortic surgery. METHODS: This prospective, single-center, observational cohort study included 54 patients undergoing elective open abdominal aortic surgery between March 2018 and April 2021. Patients were routinely treated with aspirin. IL-6 and CRP were measured preoperatively, directly after surgery, 24 hr and 48 hr postoperatively. The primary outcome was cTn release assessed by a fifth-generation high-sensitive cTn assay. Multivariable generalized linear regression models were used to evaluate the association between inflammatory biomarkers and cTn concentrations. RESULTS: Fifteen patients (27.8%) developed PMI. IL-6 directly and 24 hr postoperatively was associated with elevated cTn concentrations (1.28 [1.07-1.54], P = 0.009) and 1.75 [1.18-2.59], P = 0.006, respectively). Also, CRP directly and 24 hr postoperatively was associated with elevated cTn concentrations (1.25 [1.06-1.47], P = 0.009) and 1.61 [1.1-2.33], P = 0.013, respectively). No association was found between IL-6 or CRP and cTn concentrations when measured at 48 hr postsurgery. CONCLUSIONS: Biomarkers of inflammation are associated with elevated postoperative cTn concentrations in the early postoperative period in patients undergoing elective open abdominal aortic surgery.

Myopia management algorithm. Annexe to the article titled Update and guidance on management of myopia. European Society of Ophthalmology in cooperation with International Myopia Institute.

Myopia is becoming increasingly common in young generations all over the world, and it is predicted to become the most common cause of blindness and visual impairment in later life in the near future. Because myopia can cause serious complications and vision loss, it is critical to create and prescribe effective myopia treatment solutions that can help prevent or delay the onset and progression of myopia. The scientific understanding of myopia's causes, genetic background, environmental conditions, and various management techniques, including therapies to prevent or postpone its development and slow its progression, is rapidly expanding. However, some significant information gaps exist on this subject, making it difficult to develop an effective intervention plan. As with the creation of this present algorithm, a compromise is to work on best practices and reach consensus among a wide number of specialists. The quick rise in information regarding myopia management may be difficult for the busy eye care provider, but it necessitates a continuing need to evaluate new research and implement it into daily practice. To assist eye care providers in developing these strategies, an algorithm has been proposed that covers all aspects of myopia mitigation and management. The algorithm aims to provide practical assistance in choosing and developing an effective myopia management strategy tailored to the individual child. It incorporates the latest research findings and covers a wide range of modalities, from primary, secondary, and tertiary myopia prevention to interventions that reduce the progression of myopia.

Eye Size and Shape in Relation to Refractive Error in Children: A Magnetic Resonance Imaging Study.

Purpose: The purpose of this study was to determine the association between eye shape and volume measured with magnetic resonance imaging (MRI) and optical biometry and with spherical equivalent (SE) in children. Methods: For this study, there were 3637 10-year-old children from a population-based birth-cohort study that underwent optical biometry (IOL-master 500) and T2-weighted MRI scanning (height, width, and volume). Cycloplegic refractive error was determined by automated refraction. The MRI images of the eyes were segmented using an automated algorithm combining atlas registration with voxel classification. Associations among optical biometry, anthropometry, MRI measurements, and RE were tested using Pearson correlation. Differences between refractive error groups were tested using ANOVA. Results: The mean volume of the posterior segment was 6350 (±680) mm3. Myopic eyes (SE ≤ -0.5 diopters [D]) had 470 mm3 (P < 0.001) and 970 mm3 (P < 0.001) larger posterior segment volume than emmetropic and hyperopic eyes (SE ≥ +2.0D), respectively. The majority of eyes (77.1%) had an oblate shape, but 47.4% of myopic eyes had a prolate shape versus 3.9% of hyperopic eyes. The correlation between SE and MRI-derived posterior segment length (r -0.51, P < 0.001) was stronger than the correlation with height (r -0.30, P < 0.001) or width of the eye (r -0.10, P < 0.001). Conclusions: In this study, eye shape at 10 years of age was predominantly oblate, even in eyes with myopia. Of all MRI measurements, posterior segment length was most prominently associated with SE. Whether eye shape predicts future myopia development or progression should be investigated in longitudinal studies.

Time Spent Outdoors Partly Accounts for the Effect of Education on Myopia.

Purpose: The purpose of this study was to investigate if education contributes to the risk of myopia because educational activities typically occur indoors or because of other factors, such as prolonged near viewing. Methods: This was a two-sample Mendelian randomization study. Participants were from the UK Biobank, Avon Longitudinal Study of Parents and Children, and Generation R. Genetic variants associated with years spent in education or time spent outdoors were used as instrumental variables. The main outcome measures were: (1) spherical equivalent refractive error attained by adulthood, and (2) risk of an early age-of-onset of spectacle wear (EAOSW), defined as an age-of-onset of 15 years or below. Results: Time spent outdoors was found to have a small genetic component (heritability 9.8%) that tracked from childhood to adulthood. A polygenic score for time outdoors was associated with children's time outdoors; a polygenic score for years spent in education was inversely associated with children's time outdoors. Accounting for the relationship between time spent outdoors and myopia in a multivariable Mendelian randomization analysis reduced the size of the causal effect of more years in education on myopia to -0.17 diopters (D) per additional year of formal education (95% confidence interval [CI] = -0.32 to -0.01) compared with the estimate from a univariable Mendelian randomization analysis of -0.27 D per year (95% CI = -0.41 to -0.13). Comparable results were obtained for the outcome EAOSW. Conclusions: Accounting for the effects of time outdoors reduced the estimated causal effect of education on myopia by 40%. These results suggest about half of the relationship between education and myopia may be mediated by children not being outdoors during schooling.

Direct Environmental Lead Detection by Photoluminescent Perovskite Formation with Nanogram Sensitivity.

Although the global ban on leaded gasoline has markedly reduced lead poisoning, many other environmental sources of lead exposure, such as paint, pipes, mines, and recycling sites remain. Existing methods to identify these sources are either costly or unreliable. We report here a new, sensitive, and inexpensive lead detection method that relies on the formation of a perovskite semiconductor. The method only requires spraying the material of interest with methylammonium bromide and observing whether photoluminesence occurs under UV light to indicate the presence of lead. The method detects as little as 1.0 ng/mm2 of lead by the naked eye and 50 pg/mm2 using a digital photo camera. We exposed more than 50 different materials to our reagent and found no false negatives or false positives. The method readily detects lead in soil, paint, glazing, cables, glass, plastics, and dust and could be widely used for testing the environment and preventing lead poisoning.

Light-driven nucleation, growth, and patterning of biorelevant crystals using resonant near-infrared laser heating.

Spatiotemporal control over crystal nucleation and growth is of fundamental interest for understanding how organisms assemble high-performance biominerals, and holds relevance for manufacturing of functional materials. Many methods have been developed towards static or global control, however gaining simultaneously dynamic and local control over crystallization remains challenging. Here, we show spatiotemporal control over crystallization of retrograde (inverse) soluble compounds induced by locally heating water using near-infrared (NIR) laser light. We modulate the NIR light intensity to start, steer, and stop crystallization of calcium carbonate and laser-write with micrometer precision. Tailoring the crystallization conditions overcomes the inherently stochastic crystallization behavior and enables positioning single crystals of vaterite, calcite, and aragonite. We demonstrate straightforward extension of these principles toward other biorelevant compounds by patterning barium-, strontium-, and calcium carbonate, as well as strontium sulfate and calcium phosphate. Since many important compounds exhibit retrograde solubility behavior, NIR-induced heating may enable light-controlled crystallization with precise spatiotemporal control.

Unsupervised machine learning to classify the confinement of waves in periodic superstructures.

We propose a rigorous method to classify the dimensionality of wave confinement by utilizing unsupervised machine learning to enhance the accuracy of our recently presented scaling method [Phys. Rev. Lett.129, 176401 (2022)10.1103/PhysRevLett.129.176401]. We apply the standard k-means++ algorithm as well as our own model-based algorithm to 3D superlattices of resonant cavities embedded in a 3D inverse woodpile photonic band gap crystal with a range of design parameters. We compare their results against each other and against the direct usage of the scaling method without clustering. Since the clustering algorithms require the set of confinement dimensionalities present in the system as an input, we investigate cluster validity indices (CVIs) as a means to find these values. We conclude that the most accurate outcome is obtained by first applying direct scaling to find the correct set of confinement dimensionalities, and subsequently utilizing our model-based clustering algorithm to refine the results.

Periprocedural continuation versus interruption of oral anticoagulant drugs during transcatheter aortic valve implantation: rationale and design of the POPular PAUSE TAVI trial.

About one-third of patients undergoing transcatheter aortic valve implantation (TAVI) use oral anticoagulants (OAC), mainly due to atrial fibrillation. General guidelines advise interrupting OAC in patients with a high risk of bleeding undergoing interventions. However, preliminary observational data suggest that the continuation of OAC during TAVI is safe and may reduce the risk of periprocedural thromboembolic events. The Periprocedural Continuation Versus Interruption of Oral Anticoagulant Drugs During Transcatheter Aortic Valve Implantation (POPular PAUSE TAVI) is a multicentre, randomised clinical trial with open-label treatment and blinded endpoint assessment. Patients are randomised 1:1 to periprocedural continuation versus interruption of OAC and are stratified for vitamin K antagonist or direct oral anticoagulant use. The primary endpoint is a composite of cardiovascular mortality, all stroke, myocardial infarction, major vascular complications and type 2-4 bleeding within 30 days after TAVI, according to the Valve Academic Research Consortium-3 criteria. Secondary endpoints include separate individual and composite outcomes, quality of life and cost-effectiveness. Since continuation of OAC is associated with the ancillary benefit that it simplifies periprocedural management, the primary outcome is first analysed for non-inferiority; if non-inferiority is proven, superiority will be tested. Recruitment started in November 2020, and the trial will continue until a total of 858 patients have been included and followed for 90 days. In summary, POPular PAUSE TAVI is the first randomised clinical trial to assess the safety and efficacy of periprocedural continuation versus interruption of OAC in patients undergoing TAVI.

Enhanced secrecy in optical communication using speckle from multiple scattering layers.

We study the secrecy of an optical communication system with two scattering layers, to hide both the sender and receiver, by measuring the correlation of the intermediate speckle generated between the two layers. The binary message is modulated as spatially shaped wavefronts, and the high number of transmission modes of the scattering layers allows for many uncorrelated incident wavefronts to send the same message, making it difficult for an attacker to intercept or decode the message and thus increasing secrecy. We collect 50,000 intermediate speckle patterns and analyze their correlation distribution using the Kolmogorov-Smirnov (K-S) test. We search for further correlations using the K-Means and Hierarchical unsupervised classification algorithms. We find no correlation between the intermediate speckle and the message, suggesting a person-in-the-middle attack is not possible. This method is compatible with any digital encryption method and is applicable for codifications in optical wireless communication (OWC).

Patterning Complex Line Motifs in Thin Films Using Immersion-Controlled Reaction-Diffusion.

The discovery of self-organization principles that enable scalable routes toward complex functional materials has proven to be a persistent challenge. Here, reaction-diffusion driven, immersion-controlled patterning (R-DIP) is introduced, a self-organization strategy using immersion-controlled reaction-diffusion for targeted line patterning in thin films. By modulating immersion speeds, the movement of a reaction-diffusion front over gel films is controlled, which induces precipitation of highly uniform lines at the reaction front. A balance between the immersion speed and diffusion provides both hands-on tunability of the line spacing ( d = 10 - 300 µ m $d = 10-300 \; \umu \text{m}$ ) as well as error-correction against defects. This immersion-driven patterning strategy is widely applicable, which is demonstrated by producing line patterns of silver/silver oxide nanoparticles, silver chromate, silver dichromate, and lead carbonate. Through combinatorial stacking of different line patterns, hybrid materials with multi-dimensional patterns such as square-, diamond-, rectangle-, and triangle-shaped motifs are fabricated. The functionality potential and scalability is demonstrated by producing both wafer-scale diffraction gratings with user-defined features as well as an opto-mechanical sensor based on Moiré patterning.