Tuberculosis can be treated, prevented, and cured. Rapid, sustained declines in tuberculosis deaths in many countries during the past 50 years provide compelling evidence that ending the pandemic is ...feasible. Yet this disease—which has plagued humanity since before recorded history and has killed hundreds of millions of people over the past two centuries—remains a relentless scourge. In 2017, 1·6 million people died from tuberculosis, including 300 000 people with HIV, representing more deaths than any other infectious disease. Moreover, in many parts of the world, drugresistant forms of tuberculosis threaten struggling control efforts. The world can no longer ignore the enormous pall cast by the tuberculosis epidemic. Going forward, the global tuberculosis response must be an inclusive, comprehensive response within the broader sustainable development agenda. No one-size-fits-all approach can succeed.
There is an increasing demand in higher education institutions for training in complex environmental problems. Such training requires a careful mix of conventional methods and innovative solutions, a ...task not always easy to accomplish. In this paper we review literature on this theme, highlight relevant advances in the pedagogical literature, and report on some examples resulting from our recent efforts to teach complex environmental issues. The examples range from full credit courses in sustainable development and research methods to project-based and in-class activity units. A consensus from the literature is that lectures are not sufficient to fully engage students in these issues. A conclusion from the review of examples is that problem-based and project-based, e.g., through case studies, experiential learning opportunities, or real-world applications, learning offers much promise. This could greatly be facilitated by online hubs through which teachers, students, and other members of the practitioner and academic community share experiences in teaching and research, the way that we have done here.
In an effort to control the level of carbon nanotube exfoliation in water, pH-responsive polymers (i.e., weak polyelectrolytes) have been used as stabilizers in water. This noncovalent ...functionalization of single-walled carbon nanotubes (SWNTs) results in suspensions whose dispersion state can be altered by simply changing pH. In this study poly(acrylic acid), poly(methacrylic acid), poly(allylamine) and polyethyleneimine were used to stabilize aqueous SWNT suspensions. The results indicate that SWNTs stabilized with these polymers show a pH tailorable exfoliation and bundling in water, as evidenced by cryo-TEM images and shifts in suspension viscosity. Composite films prepared by drying these aqueous suspensions suggest that nanotube microstructure in the liquid state is largely preserved in the solid composites, with more bundled/networked structures showing higher electrical conductivity. A stabilization mechanism based upon the results obtained is proposed to explain the exfoliation and aggregation behavior of SWNTs. This method of controlling the microstructure of SWNTs in liquid state with pH could have a significant impact on the ability to tailor the microstructure and properties of composites.
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Up to 14% of patients in the United States undergoing cardiac catheterization each year experience AKI. Consistent use of risk minimization preventive strategies may improve outcomes. We hypothesized ...that team-based coaching in a Virtual Learning Collaborative (Collaborative) would reduce postprocedural AKI compared with Technical Assistance (Assistance), both with and without Automated Surveillance Reporting (Surveillance).
The IMPROVE AKI trial was a 2×2 factorial cluster-randomized trial across 20 Veterans Affairs medical centers (VAMCs). Participating VAMCs received Assistance, Assistance with Surveillance, Collaborative, or Collaborative with Surveillance for 18 months to implement AKI prevention strategies. The Assistance and Collaborative approaches promoted hydration and limited NPO and contrast dye dosing. We fit logistic regression models for AKI with site-level random effects accounting for the clustering of patients within medical centers with a prespecified interest in exploring differences across the four intervention arms.
Among VAMCs' 4517 patients, 510 experienced AKI (235 AKI events among 1314 patients with preexisting CKD). AKI events in each intervention cluster were 110 (13%) in Assistance, 122 (11%) in Assistance with Surveillance, 190 (13%) in Collaborative, and 88 (8%) in Collaborative with Surveillance. Compared with sites receiving Assistance alone, case-mix-adjusted differences in AKI event proportions were -3% (95% confidence interval CI, -4 to -3) for Assistance with Surveillance, -3% (95% CI, -3 to -2) for Collaborative, and -5% (95% CI, -6 to -5) for Collaborative with Surveillance. The Collaborative with Surveillance intervention cluster had a substantial 46% reduction in AKI compared with Assistance alone (adjusted odds ratio=0.54; 0.40-0.74).
This implementation trial estimates that the combination of Collaborative with Surveillance reduced the odds of AKI by 46% at VAMCs and is suggestive of a reduction among patients with CKD.
IMPROVE AKI Cluster-Randomized Trial (IMPROVE-AKI), NCT03556293.
We investigated short-term changes in relative paternity among a female's offspring in the long-finned squid Loligo pealeii. We conducted mating trials in the laboratory in which a single female ...mated with 2 males over the course of a few hours while laying successive egg capsules. Through microsatellite typing, we determined the males' relative paternities for the first and second egg capsules laid during each of 10 mating trials. Relative paternity of the first egg capsule was typically in favor of the first male to mate in the trial, although this was the only male to mate before the the first egg capsule was laid. When the female mated with an additional male before the second egg capsule was laid (all 10 trials), the first male to mate typically continued to achieve high relative paternity in the second capsule when the interval between first mating and second egg laying was relatively brief (i.e. 40 min or less). Dramatic differences in relative paternity were observed in the second capsule when the interval between the first mating and the laying of the second egg capsule was longer than 140 min. The present study argues against routine second and later-male sperm precedence in loliginid squids, pointing to other influences on paternity, such as the interval between insemination and egg laying.
Congenital insensitivity to pain (CIP) and hereditary sensory and autonomic neuropathies (HSAN) are clinically and genetically heterogeneous disorders exclusively or predominantly affecting the ...sensory and autonomic neurons. Due to the rarity of the diseases and findings based mainly on single case reports or small case series, knowledge about these disorders is limited. Here, we describe the molecular workup of a large international cohort of CIP/HSAN patients including patients from normally under-represented countries. We identify 80 previously unreported pathogenic or likely pathogenic variants in a total of 73 families in the >20 known CIP/HSAN-associated genes. The data expand the spectrum of disease-relevant alterations in CIP/HSAN, including novel variants in previously rarely recognized entities such as ATL3-, FLVCR1- and NGF-associated neuropathies and previously under-recognized mutation types such as larger deletions. In silico predictions, heterologous expression studies, segregation analyses and metabolic tests helped to overcome limitations of current variant classification schemes that often fail to categorize a variant as disease-related or benign. The study sheds light on the genetic causes and disease-relevant changes within individual genes in CIP/HSAN. This is becoming increasingly important with emerging clinical trials investigating subtype or gene-specific treatment strategies.
Optimization of high-throughput screening (HTS) hits resulted in the discovery of 3,5-diaryl-4,5-dihydropyrazoles as potent and selective inhibitors of KSP. Dihydropyrazole
15 is a potent, ...cell-active KSP inhibitor that induces apoptosis and generates aberrant mitotic spindles in human ovarian carcinoma cells at low nanomolar concentrations.
Optimization of high-throughput screening (HTS) hits resulted in the discovery of 3,5-diaryl-4,5-dihydropyrazoles as potent and selective inhibitors of KSP. Dihydropyrazole
15 is a potent, cell-active KSP inhibitor that induces apoptosis and generates aberrant mitotic spindles in human ovarian carcinoma cells at low nanomolar concentrations. X-ray crystallographic evidence is presented which demonstrates that these inhibitors bind in an allosteric pocket of KSP distant from the nucleotide and microtubule binding sites.
ABSTRACT We present a multi-wavelength photometric and spectroscopic study of 42 Brightest Cluster Galaxies (BCGs) in two samples of galaxy clusters chosen for a gravitational lensing study. The ...study's initial sample combines 25 BCGs from the Cluster Lensing and Supernova Survey with Hubble sample and 37 BCGs from the Sloan Giant Arcs Survey with a total redshift range of Using archival GALEX, Hubble Space Telescope, Wide-Field Infrared Survey Explorer, Herschel, and Very Large Array data we determine the BCGs' stellar mass, radio power, and star formation rates. The radio power is higher than expected if due to star formation, consistent with the BCGs being active galactic nucleus (AGN)-powered radio sources. This suggests that the AGN and star formation are both fueled by cold gas in the host galaxy. The specific star formation rate (sSFR) is low and constant with redshift. The mean sSFR is 9.42 × 10−12 yr−1, which corresponds to a mass doubling time of 105 billion years. These findings are consistent with models for hierarchical formation of BCGs, which suggest that star formation is no longer a significant channel for galaxy growth for z 1. Instead, stellar growth (of the order of a factor of at least two) during this period is expected to occur mainly via minor dry mergers.
The prefrontal cortex (PFC) has been implicated as a key brain region responsible for age-related cognitive decline. Little is known about aging-related molecular changes in PFC that may mediate ...these effects. To date, no studies have used untargeted discovery methods with integrated analyses to determine PFC molecular changes in healthy female primates. We quantified PFC changes associated with healthy aging in female baboons by integrating multiple omics data types (transcriptomics, proteomics, metabolomics) from samples across the adult age span. Our integrated omics approach using unbiased weighted gene co-expression network analysis to integrate data and treat age as a continuous variable, revealed highly interconnected known and novel pathways associated with PFC aging. We found Gamma-aminobutyric acid (GABA) tissue content associated with these signaling pathways, providing 1 potential biomarker to assess PFC changes with age. These highly coordinated pathway changes during aging may represent early steps for aging-related decline in PFC functions, such as learning and memory, and provide potential biomarkers to assess cognitive status in humans.
Dialysis-requiring acute kidney injury (AKI-D) is a documented complication of hospitalization and procedures. Temporal incidence of AKI-D and related hospital mortality in the US population has not ...been recently characterized. We describe the epidemiology of AKI-D as well as associated in-hospital mortality in the US.
Retrospective cohort of a national discharge data (n = 86,949,550) from the Healthcare Cost and Utilization Project's National Inpatient Sample, 2001-2011 of patients' hospitalization with AKI-D. Primary outcomes were AKI-D and in-hospital mortality. We determined the annual incidence rate of AKI-D in the US from 2001 to 2011. We estimated ORs for AKI-D and in-hospital mortality for each successive year compared to 2001 using multiple logistic regression models, adjusted for patient and hospital characteristics, and stratified the analyses by sex and age. We also calculated population-attributable risk of in-hospital mortality associated with AKI-D.
The adjusted odds of AKI-D increased by a factor of 1.03 (95% CI 1.02-1.04) each year. The number of AKI-D-related (19,886-34,195) in-hospital deaths increased almost 2-fold, although in-hospital mortality associated with AKI-D (28.0-19.7%) declined significantly from 2001 to 2011. Over the same period, the adjusted odds of mortality for AKI-D patients were 0.60 (95% CI 0.56-0.67). Population-attributable risk of mortality associated with AKI-D increased (2.1-4.2%) over the study period.
The incidence rate of AKI-D has increased considerably in the US since 2001. However, in-hospital mortality associated with AKI-D hospital admissions has decreased significantly.
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