An inwardly rectifying K+ channel is required for patterning.

Mutations that disrupt function of the human inwardly rectifying potassium channel KIR2.1 are associated with the craniofacial and digital defects of Andersen-Tawil Syndrome, but the contribution of Kir channels to development is undefined. Deletion of mouse Kir2.1 also causes cleft palate and digital defects. These defects are strikingly similar to phenotypes that result from disrupted TGFβ/BMP signaling. We use Drosophila melanogaster to show that a Kir2.1 homolog, Irk2, affects development by disrupting BMP signaling. Phenotypes of irk2 deficient lines, a mutant irk2 allele, irk2 siRNA and expression of a dominant-negative Irk2 subunit (Irk2DN) all demonstrate that Irk2 function is necessary for development of the adult wing. Compromised Irk2 function causes wing-patterning defects similar to those found when signaling through a Drosophila BMP homolog, Decapentaplegic (Dpp), is disrupted. To determine whether Irk2 plays a role in the Dpp pathway, we generated flies in which both Irk2 and Dpp functions are reduced. Irk2DN phenotypes are enhanced by decreased Dpp signaling. In wild-type flies, Dpp signaling can be detected in stripes along the anterior/posterior boundary of the larval imaginal wing disc. Reducing function of Irk2 with siRNA, an irk2 deletion, or expression of Irk2DN reduces the Dpp signal in the wing disc. As Irk channels contribute to Dpp signaling in flies, a similar role for Kir2.1 in BMP signaling may explain the morphological defects of Andersen-Tawil Syndrome and the Kir2.1 knockout mouse

The (im)possibility of being a breastfeeding working mother: experiences of Ecuadorian healthcare providers

Background: Throughout the twentieth century, public health agencies and expert healthcare professionals have recognized breastfeeding as the most nutritious and appropriate option for feeding infants. The Ecuadorian government, in line with international guidelines, has therefore developed laws and initiatives to improve the initiation and maintenance of breastfeeding, especially among working mothers. However, breastfeeding rates in Ecuador are low.// Methods: A qualitative methodology following social constructionist approaches was applied to explore the breastfeeding experiences of Ecuadorian women who are both mothers and healthcare professionals. Using snowball sampling, 60 healthcare professionals who breastfed their babies: 20 nurses, 20 physicians, and 20 nutritionists, took part in research interviews lasting between 30 and 92 minutes. All participants are currently offering telehealth or face-to-face consultation to their patients in Ecuador. Since Ecuador is a multicultural country, efforts were made to include participants from different regions of the country. Data gathering employed virtual semi-structured interviews including Photovoice. The interviews were carried out in Spanish, following a semi-structured topic guide. The data analysis employed constant comparative methods.// Results: The analysis produced three overarching themes: Integrating breastfeeding in life and work; Establishing space for breastfeeding at work; Negotiations and tensions. The first theme: Integrating breastfeeding in life and work addresses participants' corporeal and emotional experiences when breastfeeding. This theme also includes the participants' experiences of how they integrated their maternal identity and adapted their breastfeeding bodies to their daily routines. The second theme: Establishing space for breastfeeding at work includes the challenges that some women encounter when incorporating and seeking to combine breastfeeding in their professional identities. The third theme: Negotiations and tensions covers how this group of female healthcare professionals had to negotiate the time and space to continue breastfeeding their children while working

The (im)possibility of being a breastfeeding working mother: experiences of Ecuadorian healthcare providers

BackgroundThroughout the twentieth century, public health agencies and expert healthcare professionals have recognized breastfeeding as the most nutritious and appropriate option for feeding infants. The Ecuadorian government, in line with international guidelines, has therefore developed laws and initiatives to improve the initiation and maintenance of breastfeeding, especially among working mothers. However, breastfeeding rates in Ecuador are low.MethodsA qualitative methodology following social constructionist approaches was applied to explore the breastfeeding experiences of Ecuadorian women who are both mothers and healthcare professionals. Using snowball sampling, 60 healthcare professionals who breastfed their babies: 20 nurses, 20 physicians, and 20 nutritionists, took part in research interviews lasting between 30 and 92 minutes. All participants are currently offering telehealth or face-to-face consultation to their patients in Ecuador. Since Ecuador is a multicultural country, efforts were made to include participants from different regions of the country. Data gathering employed virtual semi-structured interviews including Photovoice. The interviews were carried out in Spanish, following a semi-structured topic guide. The data analysis employed constant comparative methods.ResultsThe analysis produced three overarching themes: Integrating breastfeeding in life and work; Establishing space for breastfeeding at work; Negotiations and tensions. The first theme: Integrating breastfeeding in life and work addresses participants' corporeal and emotional experiences when breastfeeding. This theme also includes the participants' experiences of how they integrated their maternal identity and adapted their breastfeeding bodies to their daily routines. The second theme: Establishing space for breastfeeding at work includes the challenges that some women encounter when incorporating and seeking to combine breastfeeding in their professional identities. The third theme: Negotiations and tensions covers how this group of female healthcare professionals had to negotiate the time and space to continue breastfeeding their children while working

An electron Talbot interferometer

The Talbot effect, in which a wave imprinted with transverse periodicity reconstructs itself at regular intervals, is a diffraction phenomenon that occurs in many physical systems. Here we present the first observation of the Talbot effect for electron de Broglie waves behind a nanofabricated transmission grating. This was thought to be difficult because of Coulomb interactions between electrons and nanostructure gratings, yet we were able to map out the entire near-field interference pattern, the "Talbot carpet", behind a grating. We did this using a Talbot interferometer, in which Talbot interference fringes from one grating are moire'-filtered by a 2nd grating. This arrangement has served for optical, X-ray, and atom interferometry, but never before for electrons. Talbot interferometers are particularly sensitive to distortions of the incident wavefronts, and to illustrate this we used our Talbot interferometer to measure the wavefront curvature of a weakly focused electron beam. Here we report how this wavefront curvature demagnified the Talbot revivals, and we discuss applications for electron Talbot interferometers.Comment: 5 pages, 5 figures, updated version with abstrac

Knowledge, attitudes, and practices towards COVID-19 among Venezuelans during the 2020 epidemic:An online cross-sectional survey

BACKGROUND: COVID-19 threatens health systems worldwide, but Venezuela's system is particularly vulnerable. To prevent the spread of COVID-19, individuals must adopt preventive behaviors. However, to encourage behavior change, we must first understand current knowledge, attitudes, and practices (KAPs) that inform response to this health threat. METHODS: We explored KAPs among Venezuelans using a cross-sectional, internet-based questionnaire. The questionnaire explored individuals' knowledge about COVID-19; their attitudes toward the world's and the Venezuelan authorities' abilities to control it; and their self-reported practices. We also collected demographic data. Binomial logistic regression analyses were used to predict the adoption of preventive behaviors based on demographic variables, individual knowledge level, and individual attitudes. RESULTS: 3122 individuals completed the questionnaire. Participants had a high level of knowledge about COVID-19. They expressed high levels of optimism that the world would eventually control COVID-19, but they were very pessimistic about the public authorities in Venezuela. Most participants adopted preventive practices. Binomial regression suggests younger people, less educated people, and manual laborers hold lower levels of knowledge, and these groups, as well as men, were less likely to adopt preventive practices. Knowledge, by itself, had no association with optimism and little association with self-reported practices. CONCLUSIONS: As other KAP studies in Latin America found, knowledge is not sufficient to prompt behavior change. Venezuelans' pessimism about their own country's ability should be explored in greater depth. Health promotion in Venezuela may wish to target the most at risk groups: men, younger people, less educated people, and manual laborers

Why are nonlinear fits so challenging?

Fitting model parameters to experimental data is a common yet often challenging task, especially if the model contains many parameters. Typically, algorithms get lost in regions of parameter space in which the model is unresponsive to changes in parameters, and one is left to make adjustments by hand. We explain this difficulty by interpreting the fitting process as a generalized interpretation procedure. By considering the manifold of all model predictions in data space, we find that cross sections have a hierarchy of widths and are typically very narrow. Algorithms become stuck as they move near the boundaries. We observe that the model manifold, in addition to being tightly bounded, has low extrinsic curvature, leading to the use of geodesics in the fitting process. We improve the convergence of the Levenberg-Marquardt algorithm by adding the geodesic acceleration to the usual Levenberg-Marquardt step.Comment: 4 pages, 4 figure

The geometry of nonlinear least squares with applications to sloppy models and optimization

Parameter estimation by nonlinear least squares minimization is a common problem with an elegant geometric interpretation: the possible parameter values of a model induce a manifold in the space of data predictions. The minimization problem is then to find the point on the manifold closest to the data. We show that the model manifolds of a large class of models, known as sloppy models, have many universal features; they are characterized by a geometric series of widths, extrinsic curvatures, and parameter-effects curvatures. A number of common difficulties in optimizing least squares problems are due to this common structure. First, algorithms tend to run into the boundaries of the model manifold, causing parameters to diverge or become unphysical. We introduce the model graph as an extension of the model manifold to remedy this problem. We argue that appropriate priors can remove the boundaries and improve convergence rates. We show that typical fits will have many evaporated parameters. Second, bare model parameters are usually ill-suited to describing model behavior; cost contours in parameter space tend to form hierarchies of plateaus and canyons. Geometrically, we understand this inconvenient parametrization as an extremely skewed coordinate basis and show that it induces a large parameter-effects curvature on the manifold. Using coordinates based on geodesic motion, these narrow canyons are transformed in many cases into a single quadratic, isotropic basin. We interpret the modified Gauss-Newton and Levenberg-Marquardt fitting algorithms as an Euler approximation to geodesic motion in these natural coordinates on the model manifold and the model graph respectively. By adding a geodesic acceleration adjustment to these algorithms, we alleviate the difficulties from parameter-effects curvature, improving both efficiency and success rates at finding good fits.Comment: 40 pages, 29 Figure

COVID-19 Vaccine Hesitancy in Three Latin American Countries:Reasons Given for Not Becoming Vaccinated in Colombia, Ecuador, and Venezuela

Although vaccines have been developed to prevent COVID-19, vaccine hesitancy is a significant barrier for vaccination programs. Most research on COVID-19 vaccine hesitancy has blamed misinformation and misstated concerns about effectiveness, safety, and side effects of these vaccines. The preponderance of these studies has been performed in the Global North. Although Latin American has been substantially and negatively impacted by COVID-19, few studies have examined COVID-19 vaccine hesitancy there. We explored reasons volunteered for COVID-19 vaccine hesitancy from a sample of 1,173 Colombians, Ecuadorians, and Venezuelans. Overall, COVID-19 vaccine hesitancy in these three countries is higher than desirable, but most people who are COVID-19 vaccine hesitant offered one reason or fewer. The reasons offered are diverse, including myths and exaggerations, but also individual-level contraindications for vaccination and structural barriers. Because of the diversity of reasons, single-issue mass campaigns are unlikely to bring about large shifts in COVID-19 vaccine hesitancy in Colombia, Ecuador, and Venezuela. Our data suggest that interpersonal communication, particularly in Ecuador, and addressing structural concerns, particularly in Venezuela, are likely to have the greatest impact on vaccine uptake