A Rapid Flexible Method for Determining Bile Lipids

A rapid flexible method has been developed for the quantitative determination of bile lipids In gallbladder and hepatic bile and duodenal aspirates. Quantification of bile salts involves separation of bile salt conjugates from one another and other bile lipids by thin layer chromatography. The separated salts are determined using 3-hydroxysteroid dehydrogenase and gas liquid chromatography. Cholesterol is determined in petroleum ether extracts of saponified bile by application of the Lieberman-Burchard reaction. Phospholipid phosphorus is determined in purified bile lipid extracts by oxidation followed by application of Bartlett\u27s modification of the Fiske- SubbaRow method

LArPix: Demonstration of low-power 3D pixelated charge readout for liquid argon time projection chambers

We report the demonstration of a low-power pixelated readout system designed for three-dimensional ionization charge detection and digital readout of liquid argon time projection chambers (LArTPCs). Unambiguous 3D charge readout was achieved using a custom-designed system-on-a-chip ASIC (LArPix) to uniquely instrument each pad in a pixelated array of charge-collection pads. The LArPix ASIC, manufactured in 180 nm bulk CMOS, provides 32 channels of charge-sensitive amplification with self-triggered digitization and multiplexed readout at temperatures from 80 K to 300 K. Using an 832-channel LArPix-based readout system with 3 mm spacing between pads, we demonstrated low-noise ($<$500 e$^-$ RMS equivalent noise charge) and very low-power ($<$100 $\mu$W/channel) ionization signal detection and readout. The readout was used to successfully measure the three-dimensional ionization distributions of cosmic rays passing through a LArTPC, free from the ambiguities of existing projective techniques. The system design relies on standard printed circuit board manufacturing techniques, enabling scalable and low-cost production of large-area readout systems using common commercial facilities. This demonstration overcomes a critical technical obstacle for operation of LArTPCs in high-occupancy environments, such as the near detector site of the Deep Underground Neutrino Experiment (DUNE).Comment: 19 pages, 10 figures, 1 ancillary animation. V3 includes minor revisions based on referee comment

Aberrant Calcium Signaling in Astrocytes Inhibits Neuronal Excitability in a Human Down Syndrome Stem Cell Model.

Down syndrome (DS) is a genetic disorder that causes cognitive impairment. The staggering effects associated with an extra copy of human chromosome 21 (HSA21) complicates mechanistic understanding of DS pathophysiology. We examined the neuron-astrocyte interplay in a fully recapitulated HSA21 trisomy cellular model differentiated from DS-patient-derived induced pluripotent stem cells (iPSCs). By combining calcium imaging with genetic approaches, we discovered the functional defects of DS astroglia and their effects on neuronal excitability. Compared with control isogenic astroglia, DS astroglia exhibited more-frequent spontaneous calcium fluctuations, which reduced the excitability of co-cultured neurons. Furthermore, suppressed neuronal activity could be rescued by abolishing astrocytic spontaneous calcium activity either chemically by blocking adenosine-mediated signaling or genetically by knockdown of inositol triphosphate (IP3) receptors or S100B, a calcium binding protein coded on HSA21. Our results suggest a mechanism by which DS alters the function of astrocytes, which subsequently disturbs neuronal excitability

Spatial analysis of access to and accessibility to surrounding train stations: a case study of accessibility for the elderly in Perth, Western Australia

Approximately one-fifth of Perth’s population is aged 60 or older. Projections suggest that this proportion will continue to increase as a result of the large number of children born after the World War II (1946–1964). Access to and accessibility around train stations for the aging population is and will become a more important issue as the elderly population continues to grow. The aim of the paper is to develop and apply anew measure of accessibility to train stations at a fine spatial scale, justified by the special circumstance of the elderly using a case study in Perth, Western Australia. Intercept surveys are used to collect data on factors affecting train station accessibility for patrons aged 60 years or older, at seven highly dispersed train stations. Overall accessibility is measured separately using a composite index based on three travel modes (walk-and-ride, park-and-ride and bus-and-ride). The results illustrate that key variables, such as distance from an origin to a station, walking or driving route directness, land-use diversity, service and facility quality, bus connection to train stations, all affect the accessibility to train stations for the elderly. This implies that improvements to these factors will improve accessibility for this population group

The Effect of Student-Run Vision Screenings on Ophthalmic Education and Recognition of Visual Impairment

Objective: For many in the United States, standard health insurance does not cover eyecare, leading to lapses in care and exacerbations of pre-existing conditions. Touro College of Osteopathic Medicine (TouroCOM) recognizes the importance of ocular health and offers the opportunity to engage the community through student-run vision screenings. This study aims to assess the effect of medical student-run vision screenings in supplementing pre-clinical education and to review health fair data on common vision pathologies seen in Harlem, New York.Methods: Pre- and post-surveys were administered to medical student volunteers to assess their comfort in performing a basic vision screening. Training was given in regards to screening protocols and applied at health fairs.Results: 90% of medical students (n=20) indicated discomfort in performing a basic vision screening when solely relying on their preclinical coursework. In comparison, after a training session and use during a health fair, 100% (n=20) indicated that they were comfortable with performing a vision screening.  60% of health fair participants (n=193) met referral criteria in requiring further testing or follow-up care. 100% of participants had some degree of refractive error, with 6% (n=7) having concomitant color vision abnormality and 9% (n=11) with macular abnormalities.Conclusion: Osteopathic medical students are better equipped to perform basic vision screenings and recognize visual disease with additional training and practice at health fairs. This engagement allows for early clinical experience, osteopathic outreach, and interprofessionalism. Furthermore, this provides an opportunity for community members to receive information that may guide future health decisions

Blood flow shapes intravascular pillar geometry in the chick chorioallantoic membrane

The relative contribution of blood flow to vessel structure remains a fundamental question in biology. To define the influence of intravascular flow fields, we studied tissue islands--here defined as intravascular pillars--in the chick chorioallantoic membrane. Pillars comprised 0.02 to 0.5% of the vascular system in 2-dimensional projection and were predominantly observed at vessel bifurcations. The bifurcation angle was generally inversely related to the length of the pillar (R = -0.47, P < .001). The pillar orientation closely mirrored the axis of the dominant vessel with an average variance of 5.62 ± 6.96 degrees (p = .02). In contrast, the variance of pillar orientation relative to nondominant vessels was 36.78 ± 21.33 degrees (p > .05). 3-dimensional computational flow simulations indicated that the intravascular pillars were located in regions of low shear stress. Both wide-angle and acute-angle models mapped the pillars to regions with shear less than 1 dyn/cm2. Further, flow modeling indicated that the pillars were spatially constrained by regions of higher wall shear stress. Finally, the shear maps indicated that the development of new pillars was limited to regions of low shear stress. We conclude that mechanical forces produced by blood flow have both a limiting and permissive influence on pillar development in the chick chorioallantoic membrane

Feasibility of achieving the 2025 WHO global tuberculosis targets in South Africa, China, and India: a combined analysis of 11 mathematical models

Background The post-2015 End TB Strategy proposes targets of 50% reduction in tuberculosis incidence and 75% reduction in mortality from tuberculosis by 2025. We aimed to assess whether these targets are feasible in three high-burden countries with contrasting epidemiology and previous programmatic achievements. Methods 11 independently developed mathematical models of tuberculosis transmission projected the epidemiological impact of currently available tuberculosis interventions for prevention, diagnosis, and treatment in China, India, and South Africa. Models were calibrated with data on tuberculosis incidence and mortality in 2012. Representatives from national tuberculosis programmes and the advocacy community provided distinct country-specifi c intervention scenarios, which included screening for symptoms, active case fi nding, and preventive therapy. Findings Aggressive scale-up of any single intervention scenario could not achieve the post-2015 End TB Strategy targets in any country. However, the models projected that, in the South Africa national tuberculosis programme scenario, a combination of continuous isoniazid preventive therapy for individuals on antiretroviral therapy, expanded facility-based screening for symptoms of tuberculosis at health centres, and improved tuberculosis care could achieve a 55% reduction in incidence (range 31–62%) and a 72% reduction in mortality (range 64–82%) compared with 2015 levels. For India, and particularly for China, full scale-up of all interventions in tuberculosis-programme performance fell short of the 2025 targets, despite preventing a cumulative 3·4 million cases. The advocacy scenarios illustrated the high impact of detecting and treating latent tuberculosis. Interpretation Major reductions in tuberculosis burden seem possible with current interventions. However, additional interventions, adapted to country-specifi c tuberculosis epidemiology and health systems, are needed to reach the post-2015 End TB Strategy targets at country level

Molecular and Microbial Microenvironments in Chronically Diseased Lungs Associated with Cystic Fibrosis.

To visualize the personalized distributions of pathogens and chemical environments, including microbial metabolites, pharmaceuticals, and their metabolic products, within and between human lungs afflicted with cystic fibrosis (CF), we generated three-dimensional (3D) microbiome and metabolome maps of six explanted lungs from three cystic fibrosis patients. These 3D spatial maps revealed that the chemical environments differ between patients and within the lungs of each patient. Although the microbial ecosystems of the patients were defined by the dominant pathogen, their chemical diversity was not. Additionally, the chemical diversity between locales in the lungs of the same individual sometimes exceeded interindividual variation. Thus, the chemistry and microbiome of the explanted lungs appear to be not only personalized but also regiospecific. Previously undescribed analogs of microbial quinolones and antibiotic metabolites were also detected. Furthermore, mapping the chemical and microbial distributions allowed visualization of microbial community interactions, such as increased production of quorum sensing quinolones in locations where Pseudomonas was in contact with Staphylococcus and Granulicatella, consistent with in vitro observations of bacteria isolated from these patients. Visualization of microbe-metabolite associations within a host organ in early-stage CF disease in animal models will help elucidate the complex interplay between the presence of a given microbial structure, antibiotics, metabolism of antibiotics, microbial virulence factors, and host responses.IMPORTANCE Microbial infections are now recognized to be polymicrobial and personalized in nature. Comprehensive analysis and understanding of the factors underlying the polymicrobial and personalized nature of infections remain limited, especially in the context of the host. By visualizing microbiomes and metabolomes of diseased human lungs, we reveal how different the chemical environments are between hosts that are dominated by the same pathogen and how community interactions shape the chemical environment or vice versa. We highlight that three-dimensional organ mapping methods represent hypothesis-building tools that allow us to design mechanistic studies aimed at addressing microbial responses to other microbes, the host, and pharmaceutical drugs