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This brief presents an ultra-low-power sub-1V voltage reference circuit using a self-cascode technique to improve power supply rejection ratio (PSRR) for battery-powered applications. The proposed voltage reference circuit has been fabricated in 22 nm fully-depleted silicon-on-insulator (FDSOI) CMOS technology, and it occupies an active area of 0.0104 $\text {mm}^{{2}}$ . The measured average output voltage $\text {V}_{\text {REF}}$ from 12 samples at room temperature is 598 mV with a standard deviation of 0.37%. The $\text {V}_{\text {REF}}$ shows measured average temperature coefficient $\text {TC}_{\text {avg}}$ of 61 $\text {ppm/}^{\circ }\text {C}$ over the temperature range of −40°C to 120°C, line sensitivity of 0.12%/V from 1.2V to 1.8V supply voltages, and measured PSRR of 66 dB at 10 Hz. A total power consumption is 45.6nW from a 1.2V supply voltage.

Superior mesenteric artery (SMA) syndrome is the compression of the third portion of the duodenum between the abdominal aorta and the superior mesenteric artery. Although multifactorial, the most frequent cause of SMA syndrome is significant weight loss and cachexia often induced by catabolic stress. SMA syndrome resulting from scoliosis surgery is caused by a reduction of the aortomesenteric angle and distance. Risk factors include rapid weight loss, malnutrition, and a rapid reduction in the mesenteric fat pad and are the most common causes of a decrease in the aortomesenteric angle and distance. Surgically lengthening the vertebral column can also lead to a reduction of the aortomesenteric distance, therefore, has been identified as a risk factor unique to spinal surgery. Despite a reported decline in SMA syndrome cases due to improved surgical techniques, duodenal compression is still a risk and remains a life-threatening complication of scoliosis surgery. This article is a cumulative review of the evidence of being underweight or having a low body mass index as risk factors for developing SMA syndrome following surgical scoliosis instrumentation and correction.

In medical infections such as blood sepsis and in food quality control, fast and accurate bacteria analysis is required. Using magnetic nanoparticles (MNPs) for bacterial capture and concentration is very promising for rapid analysis. When MNPs are functionalized with the proper surface chemistry, they have the ability to bind to bacteria and aid in the removal and concentration of bacteria from a sample for further analysis. This study introduces a novel approach for bacterial concentration using polydopamine (pDA), a highly adhesive polymer often purported to create antibacterial and antibiofouling coatings on medical devices. Although pDA has been generally studied for its ability to coat surfaces and reduce biofilm growth, we have found that when coated on magnetic nanoclusters (MNCs), more specifically iron oxide nanoclusters, it effectively binds to and can remove from suspension some types of bacteria. This study investigated the binding of pDA-coated MNCs (pDA-MNCs) to various Gram-negative and Gram-positive bacteria, including Staphylococcus aureus, Staphylococcus epidermidis, Pseudomonas aeruginosa, and several E. colistrains. MNCs were successfully coated with pDA, and these functionalized MNCs bound a wide variety of bacterial strains. The efficiency of removing bacteria from a suspension can range from 0.99 for S. aureusto 0.01 for an E. colistrain. Such strong capture and differential capture have important applications in collecting bacteria from dilute samples found in medical diagnostics, food and water quality monitoring, and other industries.

ABSTRACTIn this work, the limits of using spatially structured heating combined with subsequent photothermal super resolution reconstruction for the thermographic detection and resolution of internal defects are investigated. The approach is based on the application of modern high-power laser projector technology, which is used to repeatedly project varying spatially structured 2D pixel patterns to photothermally heat the object under test. After processing the generated thermographic data using nonlinear convex optimisation in conjunction with exploiting the joint-sparse nature of the defect signals within the individual measurements, a high-resolution 2D-sparse defect/inhomogeneity map is obtained. The main focus of the investigation is set on the influence of the number of individual measurements on the achievable reconstruction quality. Using numerical simulations based on an analytical representation of the forward solution to the underlying inverse problem, the convergence rate over performed measurements of the achievable reconstruction quality is determined. Finally, all findings are experimentally validated by reconstructing a set of internal defects in an additively manufactured sample. In this work, it is shown that for a variety of different defect separation distances, the projection of 50 different pixel patterns allows for a good trade-off between experimental complexity and reconstruction quality.

Recent neural models of code, such as OpenAI Codex and AlphaCode, have demonstrated remarkable proficiency at code generation due to the underlying attention mechanism. However, it often remains unclear how the models actually process code, and to what extent their reasoning and the way their attention mechanism scans the code matches the patterns of developers. A poor understanding of the model reasoning process limits the way in which current neural models are leveraged today, so far mostly for their raw prediction. To fill this gap, this work studies how the processed attention signal of three open large language models - CodeGen, InCoder and GPT-J - agrees with how developers look at and explore code when each answers the same sensemaking questions about code. Furthermore, we contribute an open-source eye-tracking dataset comprising 92 manually-labeled sessions from 25 developers engaged in sensemaking tasks. We empirically evaluate five heuristics that do not use the attention and ten attention-based post-processing approaches of the attention signal of CodeGen against our ground truth of developers exploring code, including the novel concept of follow-up attention which exhibits the highest agreement between model and human attention. Our follow-up attention method can predict the next line a developer will look at with 47% accuracy. This outperforms the baseline prediction accuracy of 42.3%, which uses the session history of other developers to recommend the next line. These results demonstrate the potential of leveraging the attention signal of pre-trained models for effective code exploration.

Cardiovascular clinical trials continue to under-represent children, older adults, females and people from ethnic minority groups relative to population disease distribution. Here we describe strategies to foster trial representativeness, with proposed actions at the levels of trial funding, design, conduct and dissemination. In particular, trial representativeness may be increased through broad recruitment strategies and site selection criteria that reflect the diversity of patients in the catchment area, as well as limiting unjustified exclusion criteria and using pragmatic designs that minimize research burden on patients (including embedded and decentralized trials). Trial communications ought to be culturally appropriate; engaging diverse people with lived experience in the co-design of some trial elements may foster this. The demographics of trialists themselves are associated with participant demographics; therefore, trial leadership must be actively diversified. Funding bodies and journals increasingly require the reporting of sociodemographic characteristics of trial participants, and regulatory bodies now provide guidance on increasing trial diversity; these steps may increase the momentum towards change. Although this Perspective focuses on the cardiovascular trial context, many of these strategies could be applied to other fields.

Point-of-care (POC) high-sensitivity cardiac troponin (hs-cTn) assays have been shown to provide similar analytical precision despite substantially shorter turnaround times compared with laboratory-based hs-cTn assays. We applied the previously developed machine learning based personalised Artificial Intelligence in Suspected Myocardial Infarction Study (ARTEMIS) algorithm, which can predict the individual probability of myocardial infarction, with a single POC hs-cTn measurement, and compared its diagnostic performance with standard-of-care pathways for rapid rule-out of myocardial infarction.

Nicotinamide adenine dinucleotide, in its oxidized (NAD+) and reduced (NADH) forms, is a reduction–oxidation (redox) co-factor and substrate for signalling enzymes that have essential roles in metabolism. The recognition that NAD+levels fall in response to stress and can be readily replenished through supplementation has fostered great interest in the potential benefits of increasing or restoring NAD+levels in humans to prevent or delay diseases and degenerative processes. However, much about the biology of NAD+and related molecules remains poorly understood. In this Review, we discuss the current knowledge of NAD+metabolism, including limitations of, assumptions about and unappreciated factors that might influence the success or contribute to risks of NAD+supplementation. We highlight several ongoing controversies in the field, and discuss the role of the microbiome in modulating the availability of NAD+precursors such as nicotinamide riboside (NR) and nicotinamide mononucleotide (NMN), the presence of multiple cellular compartments that have distinct pools of NAD+and NADH, and non-canonical NAD+and NADH degradation pathways. We conclude that a substantial investment in understanding the fundamental biology of NAD+, its detection and its metabolites in specific cells and cellular compartments is needed to support current translational efforts to safely boost NAD+levels in humans.

KIF1A-associated neurological disorder (KAND) is a neurodegenerative and often lethal ultrarare disease with a wide phenotypic spectrum associated with largely heterozygous de novo missense variants in KIF1A. Antisense oligonucleotide treatments represent a promising approach for personalized treatments in ultrarare diseases. Here we report the case of one patient with a severe form of KAND characterized by refractory spells of behavioral arrest and carrying a p.Pro305Leu variant in KIF1A, who was treated with intrathecal injections of an allele-specific antisense oligonucleotide specifically designed to degrade the mRNA from the pathogenic allele. The first intrathecal administration was complicated by an epidural cerebrospinal fluid collection, which resolved spontaneously. Otherwise, the antisense oligonucleotide was safe and well tolerated over the 9-month treatment. Most outcome measures, including severity of the spells of behavioral arrest, number of falls and quality of life, improved. There was little change in the 6-min Walk Test distance, but qualitative changes in gait resulting in meaningful reductions in falls and increasing independence were observed. Cognitive performance was stable and did not degenerate over time. Our findings provide preliminary insights on the safety and efficacy of an allele-specific antisense oligonucleotide as a possible treatment for KAND.

In the age of the digital revolution and high global competitive pressure, it is essential for companies to identify and strategically exploit automation potentials. The Automation Potential Matrix evaluates the suitability for automation and the expected business benefits. Through this holistic analysis approach, groundbreaking strategic decisions for production can be made in a very short time, while simultaneously avoiding the most significant mistakes in the selection of the form of automation.

Palladium(II) hexafluoroacetylacetonate (Pd(Hfacac)2) is known to form adducts of bases, such as lutidine (2,6-dimethylpyridine). When treated with approximately 3 equiv of lutidine, Pd(Hfacac)2yields a 1:1 complex as reported in the literature, Pd(O,O-Hfacac)(C-Hfacac)(lutidine), 1. However, when the amount of excess lutidine is increased, a new complex, 2, is formed. A single-crystal X-ray structure of 2proves it is a rare example of a dimeric palladium complex containing two Pd(Hfacac)(lutidine) fragments bridged by a dianionic trifluoroacetonate ligand, μ-CHC(O)CF3. The formation of 2is accompanied by a white precipitate determined to be a mixture of trans-Pd(O2CCF3)2(lutidine)2(3), confirming the fate of the missing trifluoroacetate fragment from the cleavage of the Hfacac ligand, and [lutidinium][Hfacac] (4). Subsequent experiments revealed the determinative role that water played in this reaction. The mechanism of cleavage of the Hfacac ligand was explored by DFT methods.

The goal of proteomics experiments is to identify proteins to observe changes in cellular processes and diseases. One challenge in proteomics is the removal of contaminants following protein extraction, which can limit protein identifications. Single-pot, solid-phase-enhanced sample preparation (SP3) is a cleanup technique in which proteins are captured on carboxylate-modified particles through a proposed hydrophilic-interaction-liquid-chromatography (HILIC)-like mechanism. Recent results have suggested that proteins are captured in SP3 due to a protein-aggregation mechanism. Solvent precipitation, single-pot, solid-phase-enhanced sample preparation (SP4) is a newer cleanup technique that employs protein aggregation to capture proteins without modified particles. We hypothesize that differences in capture mechanisms of SP3 and SP4 affect which proteins are identified by each cleanup technique. Herein, we assess the proteins identified and enriched using SP3 versus SP4 for MCF7 subcellular fractions and correlate protein capture in each method to protein hydrophobicity. Our results indicate that SP3 captures more hydrophilic proteins through a combination of HILIC-like and protein-aggregation mechanisms, while SP4 captures more hydrophobic proteins through a protein-aggregation mechanism. Ultimately, we demonstrate that protein-capture mechanisms are distinct, and the selection of a cleanup technique that yields high proteome coverage is dependent on protein-sample hydrophobicity. Data has been deposited into MassIVE (MSV000094130) and ProteomeXchange (PXD049965).

Digitale Technologien können die Versorgungsqualität und Patient*innensicherheit in Krankenhäusern erheblich verbessern. Dennoch werden sie gerade in der direkten Patient*innenversorgung aus unterschiedlichen Gründen selten nachhaltig implementiert. Eine neue Handlungsempfehlung, basierend auf einem vom Bundesministerium für Bildung und Forschung geförderten Projekt, bietet praktische Unterstützung für die erfolgreiche Implementierung von Technologien im Bereich der Pflege. Die dabei eingesetzten Tools in Form eines Canvas und einer Pocketcard sollen helfen, den Implementierungsprozess strukturiert zu planen und potenzielle Herausforderungen frühzeitig zu erkennen und zu bewältigen. Ein Beispiel aus der Praxis zeigt, wie wichtig durchdachte Strategien und die Einbindung des gesamten Teams sind. Mit der richtigen Herangehensweise können pflegerische Abläufe in Krankenhäusern optimiert werden und somit nachhaltig von digitalen Innovationen profitieren.

In the Long-Term Care (LTC) setting, comprehensive primary care is often provided by Nurse Practitioners (NPs). NPs are uniquely positioned to meet the evolving primary care needs of LTC residents. However, caring for this population requires additional education and training due to its special considerations. To meet the learning needs of NPs entering the LTC workplace, a Certificate Program was designed to enhance primary care competencies within the LTC setting. The aim of the program is to increase knowledge, capacity, and confidence of NPs to deliver quality, evidence-based, integrated, and interprofessional primary care to LTC residents. This curriculum is anticipated to address the growing need for LTC services and improve the delivery of high-quality primary care.

Introduction: Rural residency has been associated with lower reperfusion treatment rates for acute ischemic stroke in many countries. We aimed to explore urban-rural differences in IV thrombolysis rates in a small country with universal health care, and short transport times to stroke units.Patients and methods: In this nationwide cohort study, adult ischemic stroke patients registered in the Danish Stroke Registry (DSR) between 2015 and 2020 were included. The exposure was defined by residence rurality. Data from the DSR, Statistics Denmark, and the Danish Health Data Authority, were linked on the individual level using the Civil Registration Number. Adjusted treatment rates were calculated by balancing baseline characteristics using inverse probability of treatment weights.Results: Among the included 56,175 patients, prehospital delays were shortest for patients residing in capital municipalities (median 4.7 h), and longest for large town residents (median 7.1 h). Large town residents were predominantly admitted directly to a comprehensive stroke center (98.5%), whereas 30.9% of capital residents were admitted to a hospital with no reperfusion therapy available (non-RT unit). Treatment rates were similar among all non-rural residents (18.5%–18.7%), but slightly lower among rural residents (17.2% [95% CI 16.5–17.8]). After adjusting for age, sex, immigrant status, and educational attainment, rural residents reached treatment rates comparable to capital and large town residents at 18.5% (95% CI 17.7–19.4).Discussion and conclusion: While treatment rates varied minimally by urban-rural residency, substantial differences in median prehospital delay and admission to non-RT units underscored marked urban-rural differences in potential obstacles to reperfusion therapies.

According to a 2017 article by Peters and colleagues, millions of students have already demonstrated they know the material slated to be taught that year. Consequently, grade-level standards are unlikely to be appropriately challenging for these students. In this paper, we conceptually replicated and extended this prior study. Using data from schools that administered the Renaissance Star assessment in Fall 2018 and Fall 2021, we quantified pre-COVID and mid-COVID average achievement and variance in achievement in mathematics and reading in fifth grade and estimated the grade level of instruction needed for students. Our results indicate that (a) achievement dropped during COVID-19 relative to pre-COVID, but the drop in mathematics was larger, and (b) achievement variability increased during COVID-19, but the variability in reading was slightly more pronounced. Further, our results replicated Peters et al.’s (2017) results showing that large numbers of students still performed above grade level, and substantial variability in achievement was present within schools.

In the last few decades, the Ruhr Area in Germany has undergone a structural transformation that changed the landscapes of its towns and cities. Nowadays, the remnants of heavy industry are integral parts of urban semiotics articulating the cities’ industrial “soul” and heritage. In this paper, we illustrate how an analysis of residual industrial structures opens up ways of thinking about reinvented spaces that anchor cultural memory, regional identity and nostalgia. Our analytical focus is the Winding Tower of Shaft 12, preserved at Zollverein UNESCO World Heritage Site in Essen – a landmark called the “Eiffel Tower of the Ruhr Area”. Our semiotic landscape study is inspired by the framework of multimodality. We trace the industrial Tower resemiotized and remediated into visuals and material artefacts (e.g. art, logos, objects). We show how the Tower emerges as post-industrial capital which carries on the reinvention ideas and ideals that fabricate the area’s symbolic economy, allowing people to continue consuming its authenticity. Ultimately, we demonstrate how this specific example of resemiotized industrial structures has a key multimodal role in the construction and consumption of the city (image).

Empirical testing of talent development models or contextual developmental models of giftedness is enhanced by longitudinal research that considers contextual factors as well as individual/psychological factors. Relying on findings from the longitudinal TALENT project in Flanders, we aimed to shed light on the role of social-contextual factors (i.e., relationships with teachers, peers, and parents) and psychological (i.e., motivational) factors in the developmental process of transforming high cognitive ability into high achievement levels. Also, we aimed to gain insight into which developmental processes are specific to high-ability students and which are generalizable across ability levels. The findings provided longitudinal evidence for the key role of social-contextual and motivational resources in the process of academic talent development. Overall, they call for further integration of giftedness models with general developmental theories and elaboration of the role of social-contextual factors.

In this qualitative case study, we investigated the role of an advanced math curriculum with language scaffolding on the development of geometric and visual-spatial reasoning skills in young mathematically promising English learners (MPELs). Specifically, we examined the effects of providing MPELs with challenging and supportive math curriculum to facilitate the development of mathematical potential through a geometry unit. Twenty-one MPELs were randomly assigned to either an intervention or a comparison class. The data sources included audio recordings of class sessions, documents of math tasks, field notes, and test scores. Findings revealed that in the intervention class, tasks required more cognitive demands, and students were encouraged to contribute to classroom discourse more than in the comparison class. MPELs in the intervention class demonstrated greater gains in geometric reasoning compared to their peers in the comparison class. These findings underscore the point that challenging and supportive curricula can effectively nurture the mathematical potential of underrepresented gifted students.

The study of psychosocial skills is conceptualized in the field of gifted education as part of the talent development paradigm, and most terminology associated with the study of psychosocial skills is done within the framework of the talent development megamodel. Although critically important in the development of talent, empirical research on psychosocial skills as framed within the talent development paradigm is limited in the field of gifted education and more research is needed. In this paper, I present six points to consider in conducting research on psychosocial skills associated with talent development, and in particular, academic talent development. The six points are presented with an emphasis on examining ideas behind the questions of under what conditions, when, and for whom.

Mitochondria are cellular powerhouses and are crucial for cell function. However, they are vulnerable to internal and external perturbagens that may impair mitochondrial function and eventually lead to cell death. In particular, small molecules may impact mitochondrial function, and therefore, their influence on mitochondrial homeostasis is at best assessed early on in the characterization of biologically active small molecules and drug discovery. We demonstrate that unbiased morphological profiling by means of the cell painting assay (CPA) can detect mitochondrial stress coupled with the induction of an integrated stress response. This activity is common for compounds addressing different targets, is not shared by direct inhibitors of the electron transport chain, and enables prediction of mitochondrial stress induction for small molecules that are profiled using CPA.

Giant exoplanets orbiting close to their host stars are unlikely to have formed in their present configurations1. These ‘hot Jupiter’ planets are instead thought to have migrated inward from beyond the ice line and several viable migration channels have been proposed, including eccentricity excitation through angular-momentum exchange with a third body followed by tidally driven orbital circularization2,3. The discovery of the extremely eccentric (e= 0.93) giant exoplanet HD 80606 b (ref. 4) provided observational evidence that hot Jupiters may have formed through this high-eccentricity tidal-migration pathway5. However, no similar hot-Jupiter progenitors have been found and simulations predict that one factor affecting the efficacy of this mechanism is exoplanet mass, as low-mass planets are more likely to be tidally disrupted during periastron passage6–8. Here we present spectroscopic and photometric observations of TIC 241249530 b, a high-mass, transiting warm Jupiter with an extreme orbital eccentricity of e= 0.94. The orbit of TIC 241249530 b is consistent with a history of eccentricity oscillations and a future tidal circularization trajectory. Our analysis of the mass and eccentricity distributions of the transiting-warm-Jupiter population further reveals a correlation between high mass and high eccentricity.