Translational design for limited resource settings as demonstrated by Vent-Lock, a 3D-printed ventilator multiplexer

BACKGROUND: Mechanical ventilators are essential to patients who become critically ill with acute respiratory distress syndrome (ARDS), and shortages have been reported due to the novel severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). METHODS: We utilized 3D printing (3DP) technology to rapidly prototype and test critical components for a novel ventilator multiplexer system, Vent-Lock, to split one ventilator or anesthesia gas machine between two patients. FloRest, a novel 3DP flow restrictor, provides clinicians control of tidal volumes and positive end expiratory pressure (PEEP), using the 3DP manometer adaptor to monitor pressures. We tested the ventilator splitter circuit in simulation centers between artificial lungs and used an anesthesia gas machine to successfully ventilate two swine. RESULTS: As one of the first studies to demonstrate splitting one anesthesia gas machine between two swine, we present proof-of-concept of a de novo, closed, multiplexing system, with flow restriction for potential individualized patient therapy. CONCLUSIONS: While possible, due to the complexity, need for experienced operators, and associated risks, ventilator multiplexing should only be reserved for urgent situations with no other alternatives. Our report underscores the initial design and engineering considerations required for rapid medical device prototyping via 3D printing in limited resource environments, including considerations for design, material selection, production, and distribution. We note that optimization of engineering may minimize 3D printing production risks but may not address the inherent risks of the device or change its indications. Thus, our case report provides insights to inform future rapid prototyping of medical devices

Recognizing the vulnerable: Perspectives, attitudes, and interests of women with uterine factor infertility towards uterus allotransplantation

BACKGROUND: Uterine allotransplantation (UTx) is a novel therapy to allow women with uterine factor infertility (UFI) to bear their own children. To date, over 60 UTx have been performed, resulting in 15 live births. Our study investigates the attitudes, perspectives, and interests of women with UFI towards UTx. METHODS: Anonymous questionnaires were distributed electronically to women diagnosed with UFI at Johns Hopkins Hospital between the years 2003 and 2018. RESULTS: Thirty-one women with UFI were identified, resulting in 10 completed surveys. The average age was 31.7 ± 6.31 years, and the average age of diagnosis was 20 years (range 14-31); all 10 surveyed women had congenital UFI. Of note, 80% of women agreed that UTx should be an option for women with UFI, and 90% would consider receiving a UTx. The majority of the nine (90%) women who had previously heard of UTx learned about it from the news (5, 50%). When asked to rank the risks related to UTx in order of personal importance, only two women ranked themselves most important; the other woman ranked fetus and donor as more important. All women had health insurance (70% had private insurance), and 90% believed that UTx should be covered by health insurance. CONCLUSIONS: We surveyed women with UFI and found that the majority are willing to have UTx, despite the associated risks of the procedure. Taking into consideration the responses for ranking the importance of risks of the procedure, women with UFI should be considered a vulnerable population, requiring special considerations for UTx informed consents

Promiscuous binding of extracellular peptides to cell surface class I MHC protein

Algorithms derived from measurements of short-peptide (8–10 mers) binding to class I MHC proteins suggest that the binding groove of a class I MHC protein, such as K[superscript b], can bind well over 1 million different peptides with significant affinity (<500 nM), a level of ligand-binding promiscuity approaching the level of heat shock protein binding of unfolded proteins. MHC proteins can, nevertheless, discriminate between similar peptides and bind many of them with high (nanomolar) affinity. Some insights into this high-promiscuity/high-affinity behavior and its impact on immunodominant peptides in T-cell responses to some infections and vaccination are suggested by results obtained here from testing a model developed to predict the number of cell surface peptide–MHC complexes that form on cells exposed to extracellular (exogenous) peptides.Massachusetts Institute of Technology. Undergraduate Research Opportunities Progra

Heterogeneity and emergent behaviour in the vascular endothelium

The endothelium is the single layer of cells lining all blood vessels, and it is a remarkable cardiovascular control centre. Each endothelial cell has only a small number (on average six) of interconnected neighbours. Yet this arrangement produces a large repertoire of behaviours, capable of controlling numerous cardiovascular functions in a flexible and dynamic way. The endothelium regulates the delivery of nutrients and removal of waste by regulating blood flow and vascular permeability. The endothelium regulates blood clotting, responses to infection and inflammation, the formation of new blood vessels, and remodelling of the blood vessel wall. To carry out these roles, the endothelium autonomously interprets a complex environment crammed with signals from hormones, neurotransmitters, pericytes, smooth muscle cells, various blood cells, viral or bacterial infection and proinflammatory cytokines. It is generally assumed that the endothelium responds to these instructions with coordinated responses in a homogeneous population of endothelial cells. Here, we highlight evidence that shows that neighbouring endothelial cells are highly heterogeneous and display different sensitivities to various activators. Cells with various sensitivities process different extracellular signals into distinct streams of information in parallel, like a vast switchboard. Communication occurs among cells and new ‘emergent’ signals are generated that are non-linear composites of the inputs. Emergent signals cannot be predicted or deduced from the properties of individual cells. Heterogeneity and emergent behaviour bestow capabilities on the endothelial collective that far exceed those of individual cells. The implications of heterogeneity and emergent behaviour for understanding vascular disease and drug discovery are discussed

A Mysterious Island in the Digital Age: Technology and Musical Life in Ulleungdo, South Korea

This paper contributes to the growing body of ethnomusicological research about music-making on small islands, focusing on the remote South Korean island of Ulleungdo (literally, ‘Mysterious Island’). Historically, a number of factors have conspired to present serious obstacles to the Ulleungdo islanders' musical aspirations. However, since the early 1990s, enterprising amateurs have managed to generate and maintain a variety of musical activities in spite of these obstacles: church ensembles, karaoke, saxophone clubs, and more. Paralleling other island music studies, this paper seeks to show how the condition of being an Ulleungdo islander—entailing a complex of varied experiences, values, and relationships—has informed music-making over the years. However, here, the discussion remains firmly focused upon the islanders' use of technology since an acute reliance on technology has come to permeate Ulleungdo's musical life, with certain electronic devices commonly regarded as essential facilitators of musical expression. Drawing from the islanders' own testimonies, studies of Ulleungdo's cultural history, and works addressing technology's applications within and effects upon local communities, the authors explore how and why this condition of musical techno-reliance developed, how it is manifest in the present-day, and its broader implications for the island's music culture and identity

Disrupted endothelial cell heterogeneity and network organization impair vascular function in prediabetic obesity

Background: Obesity is a major risk factor for diabetes and cardiovascular diseases such as hypertension, heart failure, and stroke. Impaired endothelial function occurs in the earliest stages of obesity and underlies vascular alterations that give rise to cardiovascular disease. However, the mechanisms that link weight gain to endothelial dysfunction are ill-defined. Increasing evidence suggests that endothelial cells are not a population of uniform cells but are highly heterogeneous and are organized as a communicating multicellular network that controls vascular function. Purpose: To investigate the hypothesis that disrupted endothelial heterogeneity and network-level organization contribute to impaired vascular reactivity in obesity. Methods and Results: To study obesity-related vascular function without complications associated with diabetes, a state of prediabetic obesity was induced in rats. Small artery diameter recordings confirmed nitric-oxide mediated vasodilator responses were dependent on increases in endothelial calcium levels and were impaired in obese animals. Single-photon imaging revealed a linear relationship between blood vessel relaxation and population-wide calcium responses. Obesity did not alter the slope of this relationship, but impaired calcium responses in the endothelial cell network. The network comprised structural and functional components. The structural architecture, a hexagonal lattice network of connected cells, was unchanged in obesity. The functional network contained sub-populations of clustered specialized agonist-sensing cells from which signals were communicated through the network. In obesity there were fewer but larger clusters of sensory cells and communication path lengths between clusters increased. Communication between neighboring cells was unaltered in obesity. Altered network organization resulted in impaired, population-level calcium signaling and deficient endothelial control of vascular tone. Conclusions: The distribution of cells in the endothelial network is critical in determining overall vascular response. Altered cell heterogeneity and arrangement in obesity decreases endothelial function and provides a novel framework for understanding compromised endothelial function in cardiovascular disease

Contributions of mean and shape of blood pressure distribution to worldwide trends and variations in raised blood pressure: A pooled analysis of 1018 population-based measurement studies with 88.6 million participants

© The Author(s) 2018. Background: Change in the prevalence of raised blood pressure could be due to both shifts in the entire distribution of blood pressure (representing the combined effects of public health interventions and secular trends) and changes in its high-blood-pressure tail (representing successful clinical interventions to control blood pressure in the hypertensive population). Our aim was to quantify the contributions of these two phenomena to the worldwide trends in the prevalence of raised blood pressure. Methods: We pooled 1018 population-based studies with blood pressure measurements on 88.6 million participants from 1985 to 2016. We first calculated mean systolic blood pressure (SBP), mean diastolic blood pressure (DBP) and prevalence of raised blood pressure by sex and 10-year age group from 20-29 years to 70-79 years in each study, taking into account complex survey design and survey sample weights, where relevant. We used a linear mixed effect model to quantify the association between (probittransformed) prevalence of raised blood pressure and age-group- and sex-specific mean blood pressure. We calculated the contributions of change in mean SBP and DBP, and of change in the prevalence-mean association, to the change in prevalence of raised blood pressure. Results: In 2005-16, at the same level of population mean SBP and DBP, men and women in South Asia and in Central Asia, the Middle East and North Africa would have the highest prevalence of raised blood pressure, and men and women in the highincome Asia Pacific and high-income Western regions would have the lowest. In most region-sex-age groups where the prevalence of raised blood pressure declined, one half or more of the decline was due to the decline in mean blood pressure. Where prevalence of raised blood pressure has increased, the change was entirely driven by increasing mean blood pressure, offset partly by the change in the prevalence-mean association. Conclusions: Change in mean blood pressure is the main driver of the worldwide change in the prevalence of raised blood pressure, but change in the high-blood-pressure tail of the distribution has also contributed to the change in prevalence, especially in older age groups

Height and body-mass index trajectories of school-aged children and adolescents from 1985 to 2019 in 200 countries and territories: a pooled analysis of 2181 population-based studies with 65 million participants

Summary Background Comparable global data on health and nutrition of school-aged children and adolescents are scarce. We aimed to estimate age trajectories and time trends in mean height and mean body-mass index (BMI), which measures weight gain beyond what is expected from height gain, for school-aged children and adolescents. Methods For this pooled analysis, we used a database of cardiometabolic risk factors collated by the Non-Communicable Disease Risk Factor Collaboration. We applied a Bayesian hierarchical model to estimate trends from 1985 to 2019 in mean height and mean BMI in 1-year age groups for ages 5–19 years. The model allowed for non-linear changes over time in mean height and mean BMI and for non-linear changes with age of children and adolescents, including periods of rapid growth during adolescence. Findings We pooled data from 2181 population-based studies, with measurements of height and weight in 65 million participants in 200 countries and territories. In 2019, we estimated a difference of 20 cm or higher in mean height of 19-year-old adolescents between countries with the tallest populations (the Netherlands, Montenegro, Estonia, and Bosnia and Herzegovina for boys; and the Netherlands, Montenegro, Denmark, and Iceland for girls) and those with the shortest populations (Timor-Leste, Laos, Solomon Islands, and Papua New Guinea for boys; and Guatemala, Bangladesh, Nepal, and Timor-Leste for girls). In the same year, the difference between the highest mean BMI (in Pacific island countries, Kuwait, Bahrain, The Bahamas, Chile, the USA, and New Zealand for both boys and girls and in South Africa for girls) and lowest mean BMI (in India, Bangladesh, Timor-Leste, Ethiopia, and Chad for boys and girls; and in Japan and Romania for girls) was approximately 9–10 kg/m2. In some countries, children aged 5 years started with healthier height or BMI than the global median and, in some cases, as healthy as the best performing countries, but they became progressively less healthy compared with their comparators as they grew older by not growing as tall (eg, boys in Austria and Barbados, and girls in Belgium and Puerto Rico) or gaining too much weight for their height (eg, girls and boys in Kuwait, Bahrain, Fiji, Jamaica, and Mexico; and girls in South Africa and New Zealand). In other countries, growing children overtook the height of their comparators (eg, Latvia, Czech Republic, Morocco, and Iran) or curbed their weight gain (eg, Italy, France, and Croatia) in late childhood and adolescence. When changes in both height and BMI were considered, girls in South Korea, Vietnam, Saudi Arabia, Turkey, and some central Asian countries (eg, Armenia and Azerbaijan), and boys in central and western Europe (eg, Portugal, Denmark, Poland, and Montenegro) had the healthiest changes in anthropometric status over the past 3·5 decades because, compared with children and adolescents in other countries, they had a much larger gain in height than they did in BMI. The unhealthiest changes—gaining too little height, too much weight for their height compared with children in other countries, or both—occurred in many countries in sub-Saharan Africa, New Zealand, and the USA for boys and girls; in Malaysia and some Pacific island nations for boys; and in Mexico for girls. Interpretation The height and BMI trajectories over age and time of school-aged children and adolescents are highly variable across countries, which indicates heterogeneous nutritional quality and lifelong health advantages and risks

Rising rural body-mass index is the main driver of the global obesity epidemic in adults

Body-mass index (BMI) has increased steadily in most countries in parallel with a rise in the proportion of the population who live in cities(.)(1,2) This has led to a widely reported view that urbanization is one of the most important drivers of the global rise in obesity(3-6). Here we use 2,009 population-based studies, with measurements of height and weight in more than 112 million adults, to report national, regional and global trends in mean BMI segregated by place of residence (a rural or urban area) from 1985 to 2017. We show that, contrary to the dominant paradigm, more than 55% of the global rise in mean BMI from 1985 to 2017-and more than 80% in some low- and middle-income regions-was due to increases in BMI in rural areas. This large contribution stems from the fact that, with the exception of women in sub-Saharan Africa, BMI is increasing at the same rate or faster in rural areas than in cities in low- and middle-income regions. These trends have in turn resulted in a closing-and in some countries reversal-of the gap in BMI between urban and rural areas in low- and middle-income countries, especially for women. In high-income and industrialized countries, we noted a persistently higher rural BMI, especially for women. There is an urgent need for an integrated approach to rural nutrition that enhances financial and physical access to healthy foods, to avoid replacing the rural undernutrition disadvantage in poor countries with a more general malnutrition disadvantage that entails excessive consumption of low-quality calories.Peer reviewe