Three-Dimensional Adult Cardiac Extracellular Matrix Promotes Maturation of Human Induced Pluripotent Stem Cell-Derived Cardiomyocytes

Pluripotent stem cell-derived cardiomyocytes (CMs) have great potential in the development of new therapies for cardiovascular disease. In particular, human induced pluripotent stem cells (iPSCs) may prove especially advantageous due to their pluripotency, their self-renewal potential, and their ability to create patient-specific cell lines. Unfortunately, pluripotent stem cell-derived CMs are immature, with characteristics more closely resembling fetal CMs than adult CMs, and this immaturity has limited their use in drug screening and cell-based therapies. Extracellular matrix (ECM) influences cellular behavior and maturation, as does the geometry of the environment—twodimensional (2D) versus three-dimensional (3D). We therefore tested the hypothesis that native cardiac ECM and 3D cultures might enhance the maturation of iPSC-derived CMs in vitro. We demonstrate that maturation of iPSCderived CMs was enhanced when cells were seeded into a 3D cardiac ECM scaffold, compared with 2D culture. 3D cardiac ECMpromoted increased expression of calcium-handling genes, Junctin, CaV1.2, NCX1, HCN4, SERCA2a, Triadin, and CASQ2. Consistent with this, we find that iPSC-derived CMs in 3D adult cardiac ECM show increased calcium signaling (amplitude) and kinetics (maximum upstroke and downstroke) compared with cells in 2D. Cells in 3D culture were also more responsive to caffeine, likely reflecting an increased availability of calcium in the sarcoplasmic reticulum. Taken together, these studies provide novel strategies for maturing iPSC-derived CMs that may have applications in drug screening and transplantation therapies to treat heart disease

Drift dependence of optimal trade execution strategies under transient price impact

We give a complete solution to the problem of minimizing the expected liquidity costs in presence of a general drift when the underlying market impact model has linear transient price impact with exponential resilience. It turns out that this problem is well-posed only if the drift is absolutely continuous. Optimal strategies often do not exist, and when they do, they depend strongly on the derivative of the drift. Our approach uses elements from singular stochastic control, even though the problem is essentially non-Markovian due to the transience of price impact and the lack in Markovian structure of the underlying price process. As a corollary, we give a complete solution to the minimization of a certain cost-risk criterion in our setting

Ophthalmic infections in children presenting to Angkor Hospital for Children, Siem Reap, Cambodia.

BACKGROUND: Ophthalmic infections cause significant morbidity in Cambodian children but aetiologic data are scarce. We investigated the causes of acute eye infections in 54 children presenting to the ophthalmology clinic at Angkor Hospital for Children, Siem Reap between March and October 2012. FINDINGS: The median age at presentation was 3.6 years (range 6 days - 16.0 years). Forty two patients (77.8%) were classified as having an external eye infection, ten (18.5%) as ophthalmia neonatorum, and two (3.7%) as intra-ocular infection. Organisms were identified in all ophthalmia neonatorum patients and 85.7% of patients with an external eye infection. Pathogens were not detected in either of the intra-ocular infection patients. Most commonly isolated bacteria were Staphylococcus aureus (23 isolates), coagulase-negative staphylococci (13), coliforms (7), Haemophilus influenzae/parainfluenzae (6), Streptococcus pneumoniae (4), and Neisseria gonorrhoeae (2). Chlamydia trachomatis DNA was detected in 60% of swabs taken from ophthalmia neonatorum cases. CONCLUSIONS: This small study demonstrates the wide range of pathogens associated with common eye infections in Cambodian children. The inclusion of molecular assays improved the spectrum of detectable pathogens, most notably in neonates

Elemental Mixing State of Aerosol Particles Collected in Central Amazonia during GoAmazon2014/15

Two complementary techniques, Scanning Transmission X-ray Microscopy/Near Edge Fine Structure spectroscopy (STXM/NEXAFS) and Scanning Electron Microscopy/Energy Dispersive X-ray spectroscopy (SEM/EDX), have been quantitatively combined to characterize individual atmospheric particles. This pair of techniques was applied to particle samples at three sampling sites (ATTO, ZF2, and T3) in the Amazon basin as part of the Observations and Modeling of the Green Ocean Amazon (GoAmazon2014/5) field campaign during the dry season of 2014. The combined data was subjected to k-means clustering using mass fractions of the following elements: C, N, O, Na, Mg, P, S, Cl, K, Ca, Mn, Fe, Ni, and Zn. Cluster analysis identified 12 particle types across different sampling sites and particle sizes. Samples from the remote Amazon Tall Tower Observatory (ATTO, also T0a) exhibited less cluster variety and fewer anthropogenic clusters than samples collected at the sites nearer to the Manaus metropolitan region, ZF2 (also T0t) or T3. Samples from the ZF2 site contained aged/anthropogenic clusters not readily explained by transport from ATTO or Manaus, possibly suggesting the effects of long range atmospheric transport or other local aerosol sources present during sampling. In addition, this data set allowed for recently established diversity parameters to be calculated. All sample periods had high mixing state indices (χ) that were \u3e0.8. Two individual particle diversity (Di) populations were observed, with particles \u3c0.5 µm having a Di of ~2.4 and \u3e0.5 µm particles having a Di of ~3.6, which likely correspond to fresh and aged aerosols, respectively. The diversity parameters determined by the quantitative method presented here will serve to aid in the accurate representation of aerosol mixing state, source apportionment, and aging in both less polluted and more developed environments in the Amazon Basin

Antibiotic use and prescription and its effects on Enterobacteriaceae in the gut in children with mild respiratory infections in Ho Chi Minh City, Vietnam. A prospective observational outpatient study.

BACKGROUND AND OBJECTIVES: Treatment guidelines do not recommend antibiotic use for acute respiratory infections (ARI), except for streptococcal pharyngitis/tonsillitis and pneumonia. However, antibiotics are prescribed frequently for children with ARI, often in absence of evidence for bacterial infection. The objectives of this study were 1) to assess the appropriateness of antibiotic prescriptions for mild ARI in paediatric outpatients in relation to available guidelines and detected pathogens, 2) to assess antibiotic use on presentation using questionnaires and detection in urine 3) to assess the carriage rates and proportions of resistant intestinal Enterobacteriaceae before, during and after consultation. MATERIALS AND METHODS: Patients were prospectively enrolled in Children's Hospital 1, Ho Chi Minh City, Vietnam and diagnoses, prescribed therapy and outcome were recorded on first visit and on follow-up after 7 days. Respiratory bacterial and viral pathogens were detected using molecular assays. Antibiotic use before presentation was assessed using questionnaires and urine HPLC. The impact of antibiotic usage on intestinal Enterobacteriaceae was assessed with semi-quantitative culture on agar with and without antibiotics on presentation and after 7 and 28 days. RESULTS: A total of 563 patients were enrolled between February 2009 and February 2010. Antibiotics were prescribed for all except 2 of 563 patients. The majority were 2nd and 3rd generation oral cephalosporins and amoxicillin with or without clavulanic acid. Respiratory viruses were detected in respiratory specimens of 72.5% of patients. Antibiotic use was considered inappropriate in 90.1% and 67.5%, based on guidelines and detected pathogens, respectively. On presentation parents reported antibiotic use for 22% of patients, 41% of parents did not know and 37% denied antibiotic use. Among these three groups, six commonly used antibiotics were detected with HPLC in patients' urine in 49%, 40% and 14%, respectively. Temporary selection of 3rd generation cephalosporin resistant intestinal Enterobacteriaceae during antibiotic use was observed, with co-selection of resistance to aminoglycosides and fluoroquinolones. CONCLUSIONS: We report overuse and overprescription of antibiotics for uncomplicated ARI with selection of resistant intestinal Enterobacteriaceae, posing a risk for community transmission and persistence in a setting of a highly granular healthcare system and unrestricted access to antibiotics through private pharmacies. REGISTRATION: This study was registered at the International Standard Randomised Controlled Trials Number registry under number ISRCTN32862422: http://www.isrctn.com/ISRCTN32862422

Multi-decadal changes in mangrove extent, age and species in the Red River Estuaries of Viet Nam

This research investigated the performance of four different machine learning supervised image classifiers: artificial neural network (ANN), decision tree (DT), random forest (RF), and support vector machine (SVM) using SPOT-7 and Sentinel-1 images to classify mangrove age and species in 2019 in a Red River estuary, typical of others found in northern Viet Nam. The four classifiers were chosen because they are considered to have high accuracy, however, their use in mangrove age and species classifications has thus far been limited. A time-series of Landsat images from 1975 to 2019 was used to map mangrove extent changes using the unsupervised classification method of iterative self-organizing data analysis technique (ISODATA) and a comparison with accuracy of K-means classification, which found that mangrove extent has increased, despite a fall in the 1980s, indicating the success of mangrove plantation and forest protection efforts by local people in the study area. To evaluate the supervised image classifiers, 183 in situ training plots were assessed, 70% of them were used to train the supervised algorithms, with 30% of them employed to validate the results. In order to improve mangrove species separations, Gram-Schmidt and principal component analysis image fusion techniques were applied to generate better quality images. All supervised and unsupervised (2019) results of mangrove age, species, and extent were mapped and accuracy was evaluated. Confusion matrices were calculated showing that the classified layers agreed with the ground-truth data where most producer and user accuracies were greater than 80%. The overall accuracy and Kappa coefficients (around 0.9) indicated that the image classifications were very good. The test showed that SVM was the most accurate, followed by DT, ANN, and RF in this case study. The changes in mangrove extent identified in this study and the methods tested for using remotely sensed data will be valuable to monitoring and evaluation assessments of mangrove plantation projects

Ludwig Koch and the Music of Nature

Ludwig Koch was a pioneer of outside broadcast, natural history recording in the first half of the 20th century. This programme explores his methods, techniques and personality through archive recordings and interviews, and includes attempts t recreating his experiments using modern equipment

The genomes of two key bumblebee species with primitive eusocial organization

Background: The shift from solitary to social behavior is one of the major evolutionary transitions. Primitively eusocial bumblebees are uniquely placed to illuminate the evolution of highly eusocial insect societies. Bumblebees are also invaluable natural and agricultural pollinators, and there is widespread concern over recent population declines in some species. High-quality genomic data will inform key aspects of bumblebee biology, including susceptibility to implicated population viability threats. Results: We report the high quality draft genome sequences of Bombus terrestris and Bombus impatiens, two ecologically dominant bumblebees and widely utilized study species. Comparing these new genomes to those of the highly eusocial honeybee Apis mellifera and other Hymenoptera, we identify deeply conserved similarities, as well as novelties key to the biology of these organisms. Some honeybee genome features thought to underpin advanced eusociality are also present in bumblebees, indicating an earlier evolution in the bee lineage. Xenobiotic detoxification and immune genes are similarly depauperate in bumblebees and honeybees, and multiple categories of genes linked to social organization, including development and behavior, show high conservation. Key differences identified include a bias in bumblebee chemoreception towards gustation from olfaction, and striking differences in microRNAs, potentially responsible for gene regulation underlying social and other traits. Conclusions: These two bumblebee genomes provide a foundation for post-genomic research on these key pollinators and insect societies. Overall, gene repertoires suggest that the route to advanced eusociality in bees was mediated by many small changes in many genes and processes, and not by notable expansion or depauperation