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This case study looks both backwards and forwards at real and potential incidents and risks created by the use of various levels of self-driving vehicles. The case provides background on autonomous vehicle technology, the legal and risk management frameworks involved, and a variety of scenarios for students to consider. The scenarios provide the foundation for discussion of autonomous vehicle introductions and operations, as well as considerations for how other new technologies may be launched.

Abstract PIK3CA-related overgrowth spectrum (PROS) disorders are caused by somatic mosaic variants that result in constitutive activation of the phosphatidylinositol-3-kinase/AKT/mTOR pathway. Promising responses to molecularly targeted therapy have been reported, although identification of an appropriate agent can be hampered by the mosaic nature and corresponding low variant allele frequency of the causal variant. Moreover, our understanding of the molecular consequences of these variants—for example how they affect gene expression profiles—remains limited. Here we describe in vitro expansion of a human capillary malformation followed by molecular characterization using exome sequencing, single cell gene expression, and targeted long-read single cell RNA-sequencing in a patient with clinical features consistent with Megalencephaly-Capillary Malformation Syndrome (MCAP, a PROS condition). These approaches identified a targetable PIK3CA variant with expression restricted to PAX3+ fibroblast and undifferentiated keratinocyte populations. This study highlights the innovative combination of next-generation single cell sequencing methods to better understand unique transcriptomic profiles and cell types associated with MCAP, revealing molecular intricacies of this genetic syndrome.

Abstract Short, disturbed, and irregular sleep may contribute to blunted nocturnal blood pressure (BP) dipping, a predictor of cardiovascular disease. Black women (BLW) demonstrate less BP dipping and poorer sleep health than White women (WHW). However, it remains unclear whether device‐estimated sleep health metrics mediate the relation between race and BP dipping in young women. We hypothesized that the relation between race and BP dipping would be partly mediated by sleep health metrics of sleep duration, sleep efficiency, and sleep regularity. Participants (20 BLW, 17 WHW) were 18–29 years old, normotensive, nonobese, and without evidence of sleep disorders. Systolic and diastolic BP dipping were derived from 24‐h ambulatory BP monitoring. Habitual sleep duration and sleep efficiency were estimated via 14 days of wrist actigraphy. Sleep duration regularity was calculated as the standard deviation (SD) of nightly sleep duration (SDSD). Sleep timing regularity metrics were calculated as the SD of sleep onset and sleep midpoint (SMSD). Mediation analysis tested the mediating effect of each sleep metric on the relation between race and BP dipping. BLW experienced less systolic (P = .02) and diastolic (P = .01) BP dipping. Sleep duration (P = .14) was not different between groups. BLW had lower sleep efficiency (P .38). In conclusion, mediation pathways of sleep health metrics do not explain racial differences in nocturnal BP dipping between young BLW and WHW.

In mid-July 2020, the social media site Twitter had over 100 of its most prominent user accounts start to tweet requests to send Bitcoin to specified Bitcoin wallets. The requests promised that the Bitcoin senders would receive their money back doubled, as a gesture of charity amidst the COVID-19 pandemic. The attack appears to have been carried out by a small group of hackers, leveraging social engineering to get access to internal Twitter support tools. These tools allowed the hackers to gain full control of the high-profile user accounts and post messages on their behalf. The attack provides many paths for investigation into the prevention, response, and impacts of cybersecurity breaches.

The rapid emergence of the novel coronavirus and its impact on human behavior provoked dramatic increases in human usage of a variety of systems. These increases had the potential to stress the scalability of the systems, testing whether the system owners had designed and built those systems to cope with sudden changes in demand. This case invites students to study a variety of different types of systems, and to analyze the means by which they can or did achieve scalability, and efficiently serve their customers.

Heart failure has a poor prognosis and no curative treatment exists. Clinical trials are investigating gene- and cell-based therapies to improve cardiac function. The safe and efficient delivery of these therapies to solid organs is challenging. Herein, we demonstrate the feasibility of using an endovascular intramyocardial delivery approach to safely administer mRNA drug products and perform cell transplantation procedures in swine. Using a trans-vessel wall (TW) device, we delivered chemically modified mRNAs (modRNA) and mRNA-enhanced mesenchymal stromal cells expressing vascular endothelial growth factor A (VEGF-A) directly to the heart. We monitored and mapped the cellular distribution, protein expression, and safety tolerability of such an approach. The delivery of modRNA-enhanced cells via the TW device with different flow rates and cell concentrations marginally affect cell viability and protein expression in situ. Implanted cells were found within the myocardium for at least 3 days following administration, without the use of immunomodulation and minimal impact on tissue integrity. Finally, we could increase the protein expression of VEGF-A over 500-fold in the heart using a cell-mediated modRNA delivery system compared with modRNA delivered in saline solution. Ultimately, this method paves the way for future research to pioneer new treatments for cardiac disease.

Abstract Cardiogenic growth factors play important roles in heart development. Placental growth factor (PLGF) has previously been reported to have angiogenic effects; however, its potential role in cardiogenesis has not yet been determined. We analyze single-cell RNA-sequencing data derived from human and primate embryonic hearts and find PLGF shows a biphasic expression pattern, as it is expressed specifically on ISL1+ second heart field progenitors at an earlier stage and on vascular smooth muscle cells (SMCs) and endothelial cells (ECs) at later stages. Using chemically modified mRNAs (modRNAs), we generate a panel of cardiogenic growth factors and test their effects on enhancing cardiomyocyte (CM) and EC induction during different stages of human embryonic stem cell (hESC) differentiations. We discover that only the application of PLGF modRNA at early time points of hESC-CM differentiation can increase both CM and EC production. Conversely, genetic deletion of PLGF reduces generation of CMs, SMCs and ECs in vitro. We also confirm in vivo beneficial effects of PLGF modRNA for development of human heart progenitor-derived cardiac muscle grafts on murine kidney capsules. Further, we identify the previously unrecognized PLGF-related transcriptional networks driven by EOMES and SOX17. These results shed light on the dual cardiomyogenic and vasculogenic effects of PLGF during heart development.

Pulmonary tuberculosis is an infectious disease that is still a public health problem in the world. The study aims to determine the level of independence of tuberculosis patients and families before and after the provision of health education. The research design used in this study is a pre-experimental method with one group pretest-postest design. The population of this study was all families who had family members suffering from Pulmonary Tuberculosis and were undergoing treatment ≤ 2 months, the sampling method used was purposive sampling. The results showed the effect of health education on family independence in caring for patients with Pulmonary Tuberculosis DOTS program, with a value of p = 0.005 which means p < α (0.05). It can be concluded that there is an influence of health education on the level of family independence in caring for tuberculosis patients. The results of this study, it is expected that the public health center will socialize the implementation of home care nursing, for tuberculosis patients to always take medication regularly, and future researchers are expected to use different research methods, tests, and variables as well as large samples

Breast milk is breast milk, one of the foods that cover all elements of the baby's physical, psychological, social, and spiritual needs at the beginning of the baby's life. The study aims to determine the factors associated with exclusive breastfeeding. This type of quantitative research uses analytical surveys with cross-sectional methods. The sample size in this study was 42 respondents who fit the inclusion and exclusion criteria. The results showed that there is a relationship between knowledge and exclusive breastfeeding with a value of p = 0.016, there is a relationship between education and exclusive breastfeeding with a value of p = 0.030, there is a relationship between work and exclusive breastfeeding with a value of p = 0.000 there is a relationship between motivation and exclusive breastfeeding with a value of p = 0.032 this shows that the value of p < α = 0.05. It can be concluded that there is a relationship between knowledge, education, work, and motivation with exclusive breastfeeding. Suggestions for mothers who are breastfeeding can increase awareness to provide exclusive breastfeeding to their babies considering the role and function of breast milk from various aspects, such as aspects of maternal immunity and health, and working mothers are expected to pay more attention to exclusive breastfeeding to their babies, this is so that babies can meet the nutritional needs and growth of infant development Mothers with higher and low education must continue to breastfeed their babies and stay motivated to find out the nutritional needs of infants.

Abstract High sodium diets (HSD) can cause vascular dysfunction, in part due to increases in reactive oxygen species (ROS). Melatonin reduces ROS in healthy and clinical populations and may improve vascular function. The purpose was to determine the effect of melatonin supplementation on vascular function and ROS during 10 days of a HSD. We hypothesized that melatonin supplementation during a HSD would improve vascular function and decrease ROS levels compared to HSD alone. Twenty‐seven participants (13 M/14 W, 26.7 ± 2.9 years, BMI: 23.6 ± 2.0 kg/m2, BP: 110 ± 9/67 ± 7 mmHg) were randomized to a 10‐day HSD (6900 mg sodium/d) supplemented with either 10 mg of melatonin (HSD + MEL) or a placebo (HSD + PL) daily. Brachial artery flow‐mediated dilation, a measure of macrovascular function, (HSD + PL: 7.1 ± 3.8%; HSD + MEL: 6.7 ± 3.4%; p = 0.59) and tissue oxygenation index (TSI) reperfusion rate, a measure of microvascular reactivity, (HSD + PL: 0.21 ± 0.06%/s; HSD + MEL: 0.21 ± 0.08%/s; p = 0.97) and TSI area under the curve (HSD + PL: 199899 ± 10,863 a.u.; HSD + MEL: 20315 ± 11,348 a.u.; p = 0.17) were similar at the end of each condition. Neither nitroxide molarity (HSD + PL: 7.8 × 10−5 ± 4.1 × 10−5 mol/L; HSD + MEL: 8.7 × 10−5 ± 5.1 × 10−5 mol/L; p = 0.55) nor free radical number (HSD + PL: 8.0 × 1015 ± 4.4 × 1015; HSD + MEL: 9.0 × 1015 ± 4.9 × 1015; p = 0.51) were different between conditions. Melatonin supplementation did not alter vascular function or ROS levels while on a HSD in this sample of young healthy normotensive adults.

Background Day‐to‐day variability in sleep patterns and eating timing may disrupt circadian rhythms and has been linked with various adverse cardiometabolic outcomes. However, the extent to which variability in sleep patterns and eating timing relate to atherosclerotic development in subclinical stages remains unclear. Methods and Results Generally healthy adults (N=62, 29.3±7.3 years, 66% female) completed 14 days of sleep and dietary assessments via wrist accelerometry and photo‐assisted diet records, respectively. Variability in sleep duration, sleep onset, eating onset (time of first caloric consumption), eating offset (time of last caloric consumption), and caloric midpoint (time at which 50% of total daily calories are consumed) were operationalized as the SD across 14 days for each variable. Separate regression models evaluated the cross‐sectional associations between sleep and eating variability metrics with end‐diastolic carotid intima‐media thickness (CIMT) measured via ultrasonography. Models adjusted for age, sex, systolic blood pressure, sleep duration, and total energy intake. Each 60‐minute increase in sleep duration SD and sleep onset SD were associated with a 0.049±0.016 mm (P=0.003) and 0.048±0.017 mm (P=0.007) greater CIMT, respectively. Variability in eating onset and offset were not associated with CIMT; however, each 60‐minute increase in caloric midpoint SD was associated with a 0.033±0.015 mm greater CIMT (P=0.029). Exploratory post hoc analyses suggested that sleep duration SD and sleep onset SD were stronger correlates of CIMT than caloric midpoint SD. Conclusions Variability in sleep patterns and eating timing are positively associated with clinically relevant increases in CIMT, a biomarker of subclinical atherosclerosis, in early adulthood.

Introducción: el pie diabético (PD) representa una complicación con elevada morbimortalidad. En Argentina, carecemos de datos acerca de tasas de amputación y mortalidad relacionada a esta patología. Objetivos: describir las características de todos los pacientes adultos con diabetes mellitus (DM) que consultaron por PD durante 3 meses y evaluar su evolución a 6 meses. Materiales y métodos: se realizó un estudio descriptivo longitudinal con seguimiento a 6 meses. Resultados: se estudiaron 312 pacientes de 15 centros de Argentina. Durante el estudio, el porcentaje de amputación mayor total fue de 8,33% (IC 95; 5,5-11,9) (n=26) y el de amputación menor de 29,17% (IC 95%; 24,2-34,6) (n=91). En el seguimiento a 6 meses, el porcentaje de muerte fue de 4,49% (IC 95%; 2,5-7,4) (n=14), el 24,04% (IC 95%;19,3-29,2) presentaba la herida aún abierta (n=75), el 57,7% (IC 95%; 51,9-63,3) cicatrizó y 7,37% se perdió del seguimiento (n=23). De los pacientes que sufrieron una amputación mayor antes de los 6 meses (n=24), 5 fallecieron (20,8%) en contraste con el 3% de quienes no se amputaron (p=0,001). La amputación mayor se relacionó con la edad, el índice tobillo brazo (ITB), la escala de San Elián, la de SINBAD y la clasificación de WIfI, la isquemia y con algunos aspectos de la herida. Discusión: el conocimiento de datos locales permitirá mejorar la toma de decisiones en cuanto a políticas de salud relacionadas a la prevención y el tratamiento de los pacientes con PD.

Diabetic foot osteomyelitis (OM) is a diabetic foot ulcer complication. Usually, it is misdiagnosed and the treatment is delayed and inadequate. Delaying the treatment of these patients rises the risk of amputation. In this revision, current bibliography about this topic is updated and clinical practice recommendations are done, based on the publications and adapted to the characteristics of our country.

Abstract Engineering a conduction‐consistent cardiac patch has direct implications to biomedical research. However, there is difficulty in obtaining and maintaining a system that allows researchers to study physiologically relevant cardiac development, maturation, and drug screening due to the issues around inconsistent contractions of cardiomyocytes. Butterfly wings have special nanostructures arranged in parallel, which could help generate the alignment of cardiomyocytes to better mimic the natural heart tissue structure. Here, we construct a conduction‐consistent human cardiac muscle patch by assembling human induced pluripotent stem cell‐derived cardiomyocytes (hiPSC‐CMs) on graphene oxide (GO) modified butterfly wings. We also show this system functions as a versatile model to study human cardiomyogenesis by assembling human induced pluripotent stem cell‐derived cardiac progenitor cells (hiPSC‐CPCs) on the GO modified butterfly wings. The GO modified butterfly wing platform facilitated the parallel orientation of hiPSC‐CMs, enhanced relative maturation as well as improved conduction consistency of the cardiomyocytes. In addition, GO modified butterfly wings enhanced the proliferation and maturation characteristics of the hiPSC‐CPCs. In accordance with data obtained from RNA‐sequencing and gene signatures, assembling hiPSC‐CPCs on GO modified butterfly wings stimulated the differentiation of the progenitors into relatively mature hiPSC‐CMs. These characteristics and capabilities of GO modified butterfly wings make them an ideal platform for heart research and drug screening.

The passive leg movement (PLM) technique is a non-invasive assessment of lower-limb vascular function. PLM is methodologically simple to perform and utilizes Doppler ultrasound to determine leg blood flow (LBF) through the common femoral artery at rest and in response to passive movement of the lower leg. LBF responses to PLM have been reported to be mostly nitric oxide (NO)-mediated when performed in young adults. Moreover, PLM-induced LBF responses, as well as the NO contribution to PLM-induced LBF responses, are reduced with age and in various diseased populations, demonstrating the clinical utility of this non-invasive test. However, no PLM studies to date have included children or adolescents. Since its conception in 2015, our laboratory has performed PLM on hundreds of individuals including a large cohort of children and adolescents. Thus, the purpose of this perspective article is threefold: 1) to uniquely discuss the feasibility of performing PLM in children and adolescents, 2) to report PLM-induced LBF values from our laboratory in 7–17-year-olds, and 3) to discuss considerations for making comparisons among pediatric populations. Based on our experiences performing PLM in children and adolescents (among various other age groups), it is our perspective that PLM can feasibly be performed in this population. Further, data from our laboratory may be used to provide context for typical PLM-induced LBF values that could be observed in children and adolescents, as well as across the lifespan.

Here the authors use modified RNA and VHH libraries to generate intrabodies that target dysregulated interactions between two calcium handling proteins in failing cardiomyocytes. Heart specific expression of the intrabodies in a murine heart failure model results in improved cardiac function.

Metal hydrides are serious contenders for materials‐based hydrogen storage to overcome constraints associated with compressed or liquefied H2. Their ultimate performance is usually evaluated using intrinsic material properties without considering a systems design perspective. An illustrative case with startling implications is (LiNH2+2LiH). Using models that simulate the storage system and associated fuel cell of a light‐duty vehicle (LDV), the performance of the bulk hydrides is compared with a nanoscaled version in porous carbon (PC), (LiNH2+2LiH)@(6‐nm PC). Using experimental material properties, the simulations show that (LiNH2+2LiH)@(6‐nm PC) counterintuitively has higher usable gravimetric and volumetric capacities than the bulk counterpart on a system basis despite having lower capacities on a materials‐only basis. Nanoscaling increases the thermal conductivity and lowers the desorption enthalpy, which consequently increases heat management efficiency. In a simulated drive cycle for fuel cell‐powered LDV, the fuel cell is inoperable using bulk (LiNH2+2LiH) as the storage material but completes the drive cycle using the nanoscale material. These results challenge the notion that nanoscaling incurs mass and volume penalties. Instead, the synergistic nanoporous host‐hydride interaction can favorably modulate chemical and heat transfer properties. Moreover, a co‐design approach considering application‐specific tradeoffs is essential to accurately assess a material's potential for real‐world hydrogen storage. [ABSTRACT FROM AUTHOR]

The winter storm of late 2022 caused difficulties for many US-based airlines, but none more so than Southwest Airlines. Like other airlines, Southwest canceled flights in the early stages of the storm. Their attempted recoveries failed due to procedural and technology issues. The airline was unable to cope with the magnitude of canceled flights, aircraft and crews in the wrong places, disrupted passenger plans, and luggage separated from its owners. Over the next several days, Southwest canceled tens of thousands of flights, called in thousands of additional staff to support manual operations, and flew a reduced schedule for a time before returning to normal operations. The case provides numerous scenarios for you to analyze and research, to strengthen your understanding of the underlying concepts. [ABSTRACT FROM AUTHOR]

Often, users of information systems (both automated and manual) must analyze those systems in a "black box" fashion, without being able to see the internals of how the system is supposed to work. In this case of business process outsourcing, an insurance industry customer encounters an ongoing stream of customer service issues, with both the original provider and outsourcing organization. To understand and validate what is happening with his account, the insurance customer (Edward) and his representative (Penny) must deduce the operations, business rules, and data flows of the organizations. Most importantly, have the operations of these organizations released anyone's data inappropriately? And are these same customer service issues happening to other customers, who may not be in a position to spend the time and energy needed to catch and resolve them?

The authors survey admissions coordinators about the importance of application components in admissions decisions for economics PhD programs. The survey explores the importance of difficult-to-quantify aspects such as a targeted personal statement, strength of letters of recommendation, extracurricular activities, and related work experience. The most important aspects of an application are GPAs in math and economics, letters of recommendation, and GRE quantitative score. The strength of letters of recommendation carries more weight than the prominence of the letter writer. Top-25 programs place a higher value on undergraduate program rank (for students from both domestic and international universities) and strength of letters of recommendation.

The healthy human heart has special directional arrangement of cardiomyocytes and a unique electrical conduction system, which is critical for the maintenance of effective contractions. The precise arrangement of cardiomyocytes (CMs) along with conduction consistency between CMs is essential for enhancing the physiological accuracy of in vitro cardiac model systems. Here, we prepared aligned electrospun rGO/PLCL membranes using electrospinning technology to mimic the natural heart structure. The physical, chemical and biocompatible properties of the membranes were rigorously tested. We next assembled human induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CMs) on electrospun rGO/PLCL membranes in order to construct a myocardial muscle patch. The conduction consistency of cardiomyocytes on the patches were carefully recorded. We found that cells cultivated on the electrospun rGO/PLCL fibers presented with an ordered and arranged structure, excellent mechanical properties, oxidation resistance and effective guidance. The addition of rGO was found to be beneficial for the maturation and synchronous electrical conductivity of hiPSC-CMs within the cardiac patch. This study verified the possibility of using conduction-consistent cardiac patches to enhance drug screening and disease modeling applications. Implementation of such a system could one day lead to in vivo cardiac repair applications.

Monte Carlo simulations are the foundational technique for predicting thermodynamic properties of open systems where the process of interest involves the exchange of particles. Thus, they have been used extensively to computationally evaluate the adsorption properties of nanoporous materials and are critical for the in silico identification of promising materials for a variety of gas storage and chemical separation applications. In this work we demonstrate that a well-known biasing technique, known as "flat-histogram" sampling, can be combined with temperature extrapolation of the free energy landscape to efficiently provide significantly more useful thermodynamic information than standard open ensemble MC simulations. Namely, we can accurately compute the isosteric heat of adsorption and number of particles adsorbed for various adsorbates over an extremely wide range of temperatures and pressures from a set of simulations at just one temperature. We extend this derivation of the temperature extrapolation to adsorbates with intramolecular degrees of freedom when Rosenbluth sampling is employed. Consequently, the working capacity and isosteric heat can be computed for any given combined temperature/pressure swing adsorption process for a large range of operating conditions with both rigid and deformable adsorbates. Continuous thermodynamic properties can be computed with this technique at very moderate computational cost, thereby providing a strong case for its application to the in silico identification of promising nanoporous adsorbents.

Scientific interest in two-dimensional (2D) materials, ranging from graphene and other single layer materials to atomically thin crystals, is quickly increasing for a large variety of technological applications. While in silico design approaches have made a large impact in the study of 3D crystals, algorithms designed to discover atomically thin 2D materials from their parent 3D materials are by comparison more sparse. We hypothesize that determining how to cut a 3D material in half (i.e., which Miller surface is formed) by severing a minimal number of bonds or a minimal amount of total bond energy per unit area can yield insight into preferred crystal faces. We answer this question by implementing a graph theory technique to mathematically formalize the enumeration of minimum cut surfaces of crystals. While the algorithm is generally applicable to different classes of materials, we focus on zeolitic materials due to their diverse structural topology and because 2D zeolites have promising catalytic and separation performance compared to their 3D counterparts. We report here a simple descriptor based only on structural information that predicts whether a zeolite is likely to be synthesizable in the 2D form and correctly identifies the expressed surface in known layered 2D zeolites. The discovery of this descriptor allows us to highlight other zeolites that may also be synthesized in the 2D form that have not been experimentally realized yet. Finally, our method is general since the mathematical formalism can be applied to find the minimum cut surfaces of other crystallographic materials such as metal-organic frameworks, covalent-organic frameworks, zeolitic-imidazolate frameworks, metal oxides, etc.