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Highlights • Cognition and early cognitive development are crucial to educational and economic outcomes, but the association is not widely studied in LMICs. • Increasing cognition scores by one standard deviation is associated with a 4.5% (95% CI 2.6–9.6%) increase in wages across LMIC studies. • Higher cognitive ability increased school enrollment, academic achievement, and educational attainment across LMICs. • The benefits of early cognitive development should be considered within the context of later educational and economic returns., There is growing interest to use early cognitive ability to predict schooling and employment outcomes in low- and middle-income countries (LMICs). Rather than using educational attainment and school enrollment as predictors of future economic growth or of improving an individual’s earning potential, mounting evidence suggests that cognitive ability may be a better predictor. The relationship between cognitive ability, education, and employment are essential to predict future development in LMICs. We performed a systematic literature review and meta-analysis of the evidence regarding the relationship between cognitive ability and educational outcomes, and between cognitive ability and economic outcomes across LMICs. We searched peer-reviewed studies since 2000 that quantitatively measured these relationships. Based on an initial search of 3,766 records, we identified 14 studies, including 8 studies that examined the cognition-education link and 8 studies that assessed cognition-employment returns in LMICs. Identified studies showed that higher cognitive ability increased the probability of school enrollment, academic achievement, and educational attainment across LMICs. A meta-analysis of returns to wages from cognitive ability suggested that a standard deviation increase in cognitive test scores was associated with a 4.5% (95% CI 2.6%–9.6%) increase in wages. Investments into early cognitive development could play a critical role in improving educational and economic outcomes in LMICs. Further research should focus particularly in low-income countries with the least evidence, and examine the impact on education and economic outcomes by cognitive domains to provide more robust evidence for policy makers to take action.

Objective This article evaluates the effect of low-dose aspirin on uterine artery (UtA) Doppler, placental volume, and vascularization flow indices in low-risk pregnancy. Study Design In this secondary analysis of the TEST randomized controlled trial, low-risk nulliparous women were originally randomized at 11 weeks to: (1) routine aspirin 75 mg; (2) no aspirin; and (3) aspirin based upon the preeclampsia Fetal Medicine Foundation screening test. UtA Doppler, three-dimensional (3D) placental volume, and vascularization flow indices were assessed prior to and 6 weeks postaspirin commencement. Results A total of 546 women were included (aspirin n = 192, no aspirin n = 354). Between first and second trimesters, aspirin use was not associated with a change in UtA Doppler, placental volume, or vascular flow indices. There was no significant difference in the change in UtA Doppler pulsatility index (PI) Z-scores or notching (PI Z-score –0.2 vs. –0.2, p = 0.17), nor was there a significant change in placental volume Z-score and vascular flow indices (volume Z-score change: 0.74 vs. 0.62, p = 0.34). Conclusion Low-dose aspirin commenced at 11 weeks in low-risk women does not appear to improve uterine and placental perfusion or placental volume. Any perceived effect on uteroplacental vasculature is not reflected in changes in placental volume nor uteroplacental flow as assessed by two-dimensional and 3D ultrasound.

Purpose. The advent of mobile technology has provided a convenient method of measuring heart rate in clinical settings and athletic training with limited support. Therefore the purpose of this research was to evaluate the validity of an earpiece HR monitoring device against a previously validated chest strap HR monitoring device. Method. A convenient sample of college students (n=15), performing a modified Bruce protocol, provided 25 data samples. Heart rates obtained from both the Bioconnected wireless exercise earpieces and a Polar T31-Coded Chest Strap where compared by correlation and coefficient. The Bioconnected wireless exercise earpieces were considered to be valid if the correlation between the recorded heart rate of the Bioconnected device and the corresponding heart rate Polar T31-Coded Chest Strap measurement was r ≥0.90. Results. Five samples were corrupted due to displacement of chest strap (n=3) and dislodgement of earpiece (n=2) during testing, as such data from those tests were excluded from the correlation analysis. The remaining 20 data samples provided mean totals of 521±117 HR data points (earpiece) and 517±118 HR data points (chest strap). A strong correlation (r=0.97) between the Bioconnected wireless exercise earpieces and a Polar T31-Coded Chest Strap. Conclusions. The results of this study show that the HR measurements of the Bioconnected wireless exercise earpieces and the Polar Chest Strap are highly correlated, supporting the Bioconnected wireless exercise earpieces in monitoring HR during a GXT on a treadmill in healthy adults. However, as exercise transitioned from walking to jogging, at times, both devices had problems with displacement and loss of HR signal, suggesting the need for improved methods of securing both devices. Future research of the Bioconnected wireless exercise earpiece is required to evaluate performance in varying environments, levels of low light and increased background noise.

Massive star evolution is dominated by key physical processes such as mass loss, convection and rotation, yet these effects are poorly constrained, even on the main sequence. We utilise a detached, eclipsing binary HD166734 as a testbed for single star evolution to calibrate new MESA stellar evolution grids. We introduce a novel method of comparing theoretical models with observations in the ‘Mass-Luminosity Plane’, as an equivalent to the HRD (see Higgins & Vink 2018). We reproduce stellar parameters and abundances of HD166734 with enhanced overshooting (αov=0.5), mass loss and rotational mixing. When comparing the constraints of our testbed to the systematic grid of models we find that a higher value of αov=0.5 (rather than αov=0.1) results in a solution which is more likely to evolve to a neutron star than a black hole, due to a lower value of the compactness parameter.

Impurity ions influence mineral growth rates through a variety of kinetic and thermodynamic processes that also affect partitioning of the impurity ion between the solid and solution. Here, the effect of an impurity ion, strontium, on Barite (BaSO4) (001) growth rates was studied using a combination of high-resolution in situ microscopy with ex situ chemical imaging techniques. In the presence of strontium, ⟨120⟩ steps roughened and bifurcated. The overall Barite growth rate also decreased with increasing aqueous strontium-to-barium ratio ([Sr]/[Ba]aq) 5, steps with an apparent [010] orientation were expressed and growth in the [010] step direction led to an increase in the overall growth rate of the surface. Strontium became preferentially incorporated into the [010] step direction, rathe...

Background and objectives Ontario introduced a universal publicly-funded group A rotavirus (RVA) immunization program in August 2011, using monovalent vaccine. RVA immunization programs have decreased the incidence of RVA acute gastroenteritis in many countries but it is unclear if it will contribute to the emergence of certain genotypes. We monitored RVA trends and genotypes in Ontario before and after implementation of the publicly-funded immunization program. Methods RVA detection was conducted at Public Health Ontario Laboratories from January 2009 to December 2011 (pre-program period) and January 2012 to October 2015 (publicly-funded RVA immunization program period) and number of RVA-positive specimens and percent positivity were analysed. A convenience sample of RVA-positive stool specimens, from September 2010 to December 2011 (pre-program period) and January 2012 to June 2013 (program period), were genotyped using heminested PCR. A literature review on the burden of illness from emergent genotype was performed. Results Stool specimens showed a significant decrease in RVA percent positivity from the 36 month pre-program period (14.4%; 1537/10700) to the 46 month program period (6.1%; 548/9019). An increase in the proportion of RVA G10 among genotyped specimens, associated with five different P genotypes, from the pre-program (6.3%; 13/205) to the program (31.5%; 40/127) period was observed. Our literature review identified approximately 200 G10-positive human stool specimens from 16 different countries. Conclusions This study documented a decrease in the number of RVA-positive specimens and percent positivity after implementation of the immunization program. An unexpected increase in the proportion of RVA G10 was detected following program introduction. Ongoing RVA surveillance is important in evaluating both the long-term impact of immunization and emergence of RVA genotypes.

This work evaluated the ability of 1-ethyl-3-methylimidazolium acetate ionic liquid and potassium hydroxide loaded activated carbon sorbents to remove SO2 and NO2 under simulated atmospheric conditions containing ≤10 ppm of gas contaminants in air at 25 °C and relative humidity of 50%. The studies indicate the 1-ethyl-3-methylimidazolium acetate loaded activated carbon, [C2mim][Ac] sorbent, has superior sorption performance for SO2, with breakthrough times greater than pure activated carbon, pelletized KOH activated carbon and granulated KOH loaded activated carbon. The pelletized KOH loaded activated carbon had lowest performance indicating pelletized sorbents are not ideal for use in high flow rate applications such as fuel cells. The SO2 concentration significantly impacted the breakthrough times of the [C2mim][Ac] sorbent, low SO2 concentration resulted in the longest break through times but lowest sorption capacities. The granulated KOH activated carbon and pure activated carbon had highest NO2 break through times compared to [C2mim][Ac] sorbents. The simultaneous SO2 and NO2 sorption studies indicated that the [C2mim][Ac] sorbent had greater selectivity for SO2 than NO2 compared to the KOH sorbents, as evidenced by high breakthrough times for SO2 compared to NO2. Theoretical studies using DFT-B3LYP were performed to elucidate the favored binding interactions of the [C2mim][Ac] with acidic gas contaminants. Theory indicates acidic gas contaminants preferentially interact strongly with the oxygen atoms of the acetate anion compared to the imidazole cation. The computational work also confirmed experiments showing high selectivity of the 1-ethyl-3-methylimidazolium acetate ionic liquid sorbent for SO2 compared to NO2.

Although minerals are known to affect the environmental fate and transformation of heavy-metal ions, little is known about their interaction with the heavily exploited silver nanoparticles (AgNPs). Proposed here is a combination of hitherto under-utilized micro-Raman-based mapping and chemometric methods for imaging the distribution of AgNPs on various mineral surfaces and their molecular interaction mechanisms. The feasibility of the Raman-based imaging method was tested on two macro- and microsized mineral models, muscovite [KAl2(AlSi3O10)(OH)2] and corundum (α-Al2O3), under key environmental conditions (ionic strength and pH). Both AgNPs– and AgNPs+ were found to covalently attach to corundum (pHpzc = 9.1) through the formation of Ag–O–Al– bonds and thereby to potentially experience reduced environmental mobility. Because label-free Raman imaging showed no molecular interactions between AgNPs– and muscovite (pHpzc = 7.5), a label-enhanced Raman imaging approach was developed for mapping the scarce spat...

Proteasomal shuttle factor UBQLN2 is recruited to stress granules and undergoes liquid-liquid phase separation (LLPS) into protein-containing droplets. Mutations to UBQLN2 have recently been shown to cause dominant X-linked inheritance of amyotrophic lateral sclerosis (ALS) and ALS/dementia. Interestingly, most of these UBQLN2 mutations reside in its proline-rich (Pxx) region, an important modulator of LLPS. Here, we demonstrated that ALS-linked Pxx mutations differentially affect UBQLN2 LLPS, depending on both amino acid substitution and sequence position. Using size-exclusion chromatography, analytical ultracentrifugation, microscopy, and NMR spectroscopy, we determined that those Pxx mutants that enhanced UBQLN2 oligomerization decreased saturation concentrations needed for LLPS and promoted solid-like and viscoelastic morphological changes to UBQLN2 liquid assemblies. Ubiquitin disassembled all LLPS-induced mutant UBQLN2 aggregates. We postulate that the changes in physical properties caused by ALS-linked Pxx mutations modify UBQLN2 behavior in vivo, possibly contributing to aberrant stress granule morphology and dynamics, leading to formation of inclusions, pathological characteristics of ALS.

We observe EIT in a V-system in a thermal rubidium-87 vapour in the hyperfine Paschen-Back regime, realised with a 0.6 T axial magnetic field. In this regime energy levels are no longer degenerate and EIT features from different initial states are distinct, which we show produces a much cleaner feature than without a magnetic field. We compare our results to a model using the time-dependent Lindblad master equation, and having averaged over a distribution of interaction times, see good qualitative agreement for a range of pump Rabi frequencies. Excited state decay into both ground states is shown to play a prominent role in the generation of the transparency feature, which arises mainly due to transfer of population into the ground state not coupled by the probe beam. We use the model to investigate the importance of coherence in this feature, showing that its contribution is more significant at smaller pump Rabi frequencies., 8 pages, 8 figures

To better understand the role of spectator ions in barite growth, the kinetics of step edge growth on barite (001) surfaces were studied under various salt solutions. Hydrothermal atomic force microscopy (HAFM) was used to investigate the effect of background electrolytes (NaCl, NaBr, and NaNO3) as a function of saturation index and ionic strength (I) on barite growth sourced at dislocations at 108 °C. Results demonstrate that hillock morphology is affected by I, as well as type of anion, where the prevalence of steps aligned on the [010] direction is highest under Cl–. There is a modest increase in kinetic coefficient of 55–130% with a 10-fold increase in I for each salt. In comparing the kinetic coefficients of the salts at low ionic strength (0.01 M), there is a moderate difference, suggesting that the anion may play a role in barium attachment.

We present first results of a new heterodyne spectrometer dedicated to high-resolution spectroscopy of molecules of astrophysical importance. The spectrometer, based on a roomtemperature heterodyne receiver, is sensitive to frequencies between 75 and 110 GHz with an instantaneous bandwidth of currently 2.5 GHz in a single sideband. The system performance, in particular the sensitivity and stability, is evaluated. Proof of concept of this spectrometer is demonstrated by recording the emission spectrum of methyl cyanide, CH3CN. Compared to state-of-the-art radio telescope receivers the instrument is less sensitive by about one order of magnitude. Nevertheless, the capability for absolute intensity measurements can be exploited in various experiments, in particular for the interpretation of the ever richer spectra in the ALMA era. The ease of operation at room-temperature allows for long time integration, the fast response time for integration in chirped pulse instruments or for recording time dependent signals. Future prospects as well as limitations of the receiver for the spectroscopy of complex organic molecules (COMs) are discussed., Comment: 14 pages, 7 figures, IAUS-332 Astrochemistry VII, Through the Cosmos from Galaxies to Planets, 2017

Belize recently committed to establishing territorial use rights in fisheries (TURFs), called "managed access" in Belize, throughout its territorial waters. While more remains to be done to ensure that scaling is successful, this national commitment and the design of a national system of managed access areas are important milestones in the expansion of rights-based fishery management in Belize. Theoretical work and empirical studies have yielded principles for scaling conservation innovations, many of which were applied in Belize over 3 yrs to achieve these milestones. Two pilot sites were established in 2011 and encompassed varied ecological and social conditions to maximize learning applicable to scaling to diverse sites. Participatory processes were used to identify fishery management challenges as perceived by fishers, managers, and other stakeholders, and to build consensus on solutions. A scaling team consisting of fishers, scientists, non-governmental organizations, community-based organizations, and government representatives with dedicated resources for scaling was formed. Our case study suggests that scaling principles derived from theoretical considerations and empirical analysis have contributed to the scaling of managed access in Belize, which is expected to result in significant conservation, social, and economic benefits. This in turn suggests that these principles may be relatively robust and perhaps can be applied elsewhere to scale conservation initiatives. Our case study also suggests that careful consideration of new information and changing conditions accompanied by appropriate decisions and changes in tactics and strategy are important for successful scaling.

Animal waste has been studied as a potential fuel source via anaerobic digestion. Feces have also been used to inoculate biodigesters. Biodigesters are a waste treatment solution that use anaerobic digestion to convert organic matter into methane. They utilize microbes to break down organic matter into substrates which are then converted into methane as fuel. The final step’s productivity depends on the methanogen content of the biodigester. This study evaluated the feces of captive animals for use as a methanogenic inoculum. The aim was to assess the potential of different feces for methanogen contribution through a literature review and sample analysis via fluorescence microscopy to observe F420 autofluorescence. Coenzyme F420 is a fluorescent coenzyme involved in redox reactions in methanogens and is used in their identification and observation. The samples were from herbivores in the orders Rodentia (rodents), Lagomorpha (rabbits), Perissodactyla (odd-toed ungulates), Artiodactyla (even-toed ungulates), and Diprotodontia (some marsupials). The literature review favored goats and sheep over the other animals in the study. The feces from each animal species tested were observed to have some methanogen presence, but the levels were low and differences were not discernible. Overall, the results of the sample analyses were inconclusive due to the scarcity of methanogens and obscuration due to foliage fragments. Keywords: Fecal, Methanogens, Coenzyme F420, Anaerobic digestion, Biodigester, Inoculum

Residual neuromuscular block has been associated with postoperative pulmonary complications. We hypothesised that sugammadex reduces postoperative pulmonary complications in patients aged ≥70 yr having surgery ≥3 h, compared with neostigmine.Patients were enrolled in an open-label, assessor-blinded, randomised, controlled trial. At surgical closure, subjects were equally randomised to receive sugammadex 2 mg kgOf the 200 subjects randomised, 98 received sugammadex and 99 received neostigmine. There was no significant difference in the primary endpoint of postoperative pulmonary complications despite a signal towards reduced incidence for sugammadex (33% vs 40%; odds ratio [OR]=0.74; 95% confidence interval [CI]=[0.40, 1.37]; P=0.30) compared with neostigmine. Sugammadex decreased residual neuromuscular block (10% vs 49%; OR=0.11, 95% CI=[0.04, 0.25]; P0.001). Phase 1 recovery time was comparable between sugammadex (97.3 min [standard deviation, sd=54.3]) and neostigmine (110.0 min [sd=62.0]), difference -12.7 min (95% CI, [-29.2, 3.9], P=0.13). In an exploratory analysis, there were fewer 30 day hospital readmissions in the sugammadex group compared with the neostigmine group (5% vs 15%; OR=0.30, 95% CI=[0.08, 0.91]; P=0.03).In older adults undergoing prolonged surgery, sugammadex was associated with a 40% reduction in residual neuromuscular block, a 10% reduction in 30 day hospital readmission rate, but no difference in the occurrence of postoperative pulmonary complications. Based on this exploratory study, larger studies should determine whether sugammadex may reduce postoperative pulmonary complications and 30 day hospital readmissions.NCT02861131.

Neutrophilic inflammation with prolonged neutrophil survival is common to many inflammatory conditions, including chronic obstructive pulmonary disease (COPD). There are few specific therapies that reverse neutrophilic inflammation, but uncovering mechanisms regulating neutrophil survival is likely to identify novel therapeutic targets. Screening of 367 kinase inhibitors in human neutrophils and a zebrafish tail fin injury model identified ErbBs as common targets of compounds that accelerated inflammation resolution. The ErbB inhibitors gefitinib, CP-724714, erbstatin and tyrphostin AG825 significantly accelerated apoptosis of human neutrophils, including neutrophils from people with COPD. Neutrophil apoptosis was also increased in Tyrphostin AG825 treated-zebrafish in vivo. Tyrphostin AG825 decreased peritoneal inflammation in zymosan-treated mice, and increased lung neutrophil apoptosis and macrophage efferocytosis in a murine acute lung injury model. Tyrphostin AG825 and knockdown of egfra and erbb2 by CRISPR/Cas9 reduced inflammation in zebrafish. Our work shows that inhibitors of ErbB kinases have therapeutic potential in neutrophilic inflammatory disease., eLife digest Chronic obstructive pulmonary disease (or COPD) is a serious condition that causes the lungs to become inflamed for long periods of time, leading to permanent damage of the airways. Immune cells known as neutrophils promote inflammation after an injury, or during an infection, to aid the healing process. However, if they are active for too long, they may also cause tissue damage and drive inflammatory diseases including COPD. To limit damage to the body, neutrophils usually have a very short lifespan and die by a regulated process known as apoptosis. Finding ways to stimulate apoptosis in neutrophils may be key to developing better treatments for inflammatory diseases. Cells contain many enzymes known as kinases that control apoptosis and other cell processes. Drugs that inhibit specific kinases are effective treatments for some types of cancer and other conditions, and new kinase-inhibiting drugs are currently being developed. However, it remains unclear which kinases regulate apoptosis in neutrophils or which kinase-inhibiting drugs may have the potential to treat COPD and other inflammatory diseases. To address these questions, Rahman et al. tested over 350 kinase-inhibiting drugs to identify ones that promote apoptosis in neutrophils. The experiments showed that human neutrophils treated with drugs that inhibit the ErbB family of kinases died by apoptosis more quickly than untreated neutrophils. Next, Rahman et al. used zebrafish with injured tail fins as models to study inflammation. Zebrafish treated with one of these drugs – known as Tyrphostin AG825 – had lower levels of inflammation and their neutrophils underwent apoptosis more frequently than untreated zebrafish. Since drugs can have off-target effects, Rahman et al. went on to show using gene-editing technology that reducing the activity of two genes that encode ErbB kinases in zebrafish also decreased the levels of inflammation in the fish. Further experiments used mice that develop inflammation in the lungs similar to COPD in humans. As expected, neutrophils in the lungs of mice treated with Tyrphostin AG825 underwent apoptosis more frequently than those in untreated mice. These dead neutrophils were effectively cleared by other immune cells called macrophages, which also helps limit damage caused by neutrophils. Together, these findings show that Tyrphostin AG825 and other drugs that inhibit ErbB kinases help to reduce inflammation by promoting the death of neutrophils. Since several of these drugs are already used to treat human cancers, it may be possible in the future to repurpose them for use in people with COPD and other long-term inflammatory diseases. Determining whether this is possible is an aim for future studies.

Tissue-resident memory T cells (T(RM) cells) are a novel population of tissue-restricted antigen-specific T cells. T(RM) cells are induced by pathogens and promote host defense against secondary infections. Although T(RM) cells cannot be detected in circulation, they are the major memory CD4(+) and CD8(+) T-cell population in tissues in mice and humans. Murine models of CD8(+) T(RM) cells have shown that CD8(+) T(RM) cells maintain tissue residency via CD69 and though tumor growth factor β-dependent induction of CD103. In contrast to CD8(+) T(RM) cells, there are few models of CD4(+) T(RM) cells. Thus, much less is known about the factors regulating the induction, maintenance, and host defense functions of CD4(+) T(RM) cells. Citrobacter rodentium is known to induce IL-17(+) and IL-22(+) CD4(+) T cells (T(h)17 and T(h)22 cells, respectively). Moreover, data from IL-22 reporter mice show that most IL-22(+) cells in the colon 3 months after C. rodentium infection are CD4(+) T cells. This collectively suggests that C. rodentium may induce CD4(+) T(RM) cells. Here, we demonstrate that C. rodentium induces a population of IL-17A(+) CD4(+) T cells that are tissue restricted and antigen specific, thus meeting the criteria of CD4(+) T(RM) cells. These cells expand and are a major source of IL-22 during secondary C. rodentium infection, even before the T-cell phase of the host response in primary infection. Finally, using FTY 720, which depletes circulating naive and effector T cells but not tissue-restricted T cells, we show that these CD4(+) T(RM) cells can promote host defense.

Crohn’s disease (CD) is one type of inflammatory bowel disease where both inflammation and fibrosis cause the thickening of the bowel wall and development of the strictures. Accurate assessment of the strictures is critical for the management of CD because the fibrotic strictures must be removed surgically. In this study, a prototype capsule-shaped acoustic resolution photoacoustic (PA) endoscope, which can perform mulitwavelength side-view scanning, was developed to characterize the intestinal strictures of CD. The imaging performance of the probe was tested in phantom experiments and a rabbit trinitrobenzene sulfonic acid (TNBS) model with acute (inflammatory only) or chronic (mixed fibrotic and inflammatory) colitis in vivo. The motion artifacts due to intestinal peristalsis and the respiratory motion of the animals were compensated to improve image qualities. Quantitative molecular component images derived from multi-wavelength PA measurements of normal, acute and chronic intestinal strictures demonstrated statistically significant differences among the three groups that were confirmed by histopathology. A longitudinal study demonstrated the capability of the system in monitoring the development of fibrosis. The results suggest that the proposed novel, capsule-shaped acoustic resolution PA endoscope can be used to characterize fibrostenotic disease in vivo.

SUMMARY Hepatic lipid accumulation in obesity correlates with the severity of hyperinsulinemia and systemic insulin resistance. Obesity-induced hepatocellular lipid accumulation results in hepatocyte depolarization. We have established that hepatocyte depolarization depresses hepatic afferent vagal nerve firing, increases GABA release from liver slices, and causes hyperinsulinemia. Preventing hepatic GABA release or eliminating the ability of the liver to communicate to the hepatic vagal nerve ameliorates the hyperinsulinemia and insulin resistance associated with diet-induced obesity. In people with obesity, hepatic expression of GABA transporters is associated with glucose infusion and disposal rates during a hyperinsulinemic euglycemic clamp. Single-nucleotide polymorphisms in hepatic GABA re-uptake transporters are associated with an increased incidence of type 2 diabetes mellitus. Herein, we identify GABA as a neuro-hepatokine that is dysregulated in obesity and whose release can be manipulated to mute or exacerbate the glucoregulatory dysfunction common to obesity., Graphical Abstract, In brief Geisler et al. show that obesity depolarizes hepatocytes, favoring transport-mediated GABA release. Hyperpolarizing hepatocytes limits transporter-mediated GABA release. GABA released by the liver decreases vagal afferent nerve activity, causing an increase in serum insulin and insulin resistance. Thus, electrogenic GABA transporters can be modulated to affect glucose homeostasis.

Background: Over 10% of antibiotics in low- and middle-income countries (LMICs) are substandard or falsified. Detection of poor-quality antibiotics via the gold standard method, high-performance liquid chromatography (HPLC), is slow and costly. Paper analytical devices (PADs) and antibiotic paper analytical devices (aPADs) have been developed as an inexpensive way to estimate antibiotic quality in LMICs. Aim: To model the impact of using a rapid screening tools, PADs/aPADs, to improve the quality of amoxicillin used for treatment of childhood pneumonia in Kenya. Methods: We developed an agent-based model, ESTEEM (Examining Screening Technologies with Economic Evaluations for Medicines), to estimate the effectiveness and cost savings of incorporating PADs and aPADs in amoxicillin quality surveillance in Kenya. We compared the current testing scenario (batches of entire samples tested by HPLC) with an expedited HPLC scenario (testing smaller batches at a time), as well as a screening scenario using PADs/aPADs to identify poor-quality amoxicillin followed by confirmatory analysis with HPLC. Results: Scenarios using PADs/aPADs or expedited HPLC yielded greater incremental benefits than the current testing scenario by annually averting 586 (90% uncertainty range (UR) 364–874) and 221 (90% UR 126–332) child pneumonia deaths, respectively. The PADs/aPADs screening scenario identified and removed poor-quality antibiotics faster than the expedited or regular HPLC scenarios, and reduced costs significantly. The PADs/aPADs scenario resulted in an incremental return of $14.9 million annually compared with the reference scenario of only using HPLC. Conclusion: This analysis shows the significant value of PADs/aPADs as a medicine quality screening and testing tool in LMICs with limited resources.

Data gathered by electrical resistivity tomography (ERT) and ground-penetrating radar (GPR) were used to produce a three-dimensional image of subsurface soft-sediment deformation structures developed on the modern Lake Powell delta at Hite, Utah. ERT and GPR lines were run orthogonal across the crater. ERT resolved a low-resistivity layer up to 2 m thick in the area near the vents within the crater. This low-resistivity layer thins toward the margins representing clays ejected from the vents. Below and adjacent to this layer is a high-resistivity layer that reflects delta top and pro-delta sands. The deepest zone recognized in the ERT profiles consists of a low-resistivity layer, clay deposits that accumulated during the maximum lake high stand. This clay zone is connected to the vent within the crater by a conduit that changes diameter vertically. GPR profiles recognized the presence of collapse features restricted to the proximity of the vent. The geometry of the model is consistent with those proposed for marine pockmarks that can be generated seismically or aseismically with the exception of subaerial exposure after the dome stage development.

The rate of growth of ionic minerals from solutions with varying aqueous cation:anion ratios may result in significant errors in mineralization rates predicted by commonly-used affinity-based rate equations. To assess the potential influence of solute stoichiometry on barite growth, step velocities on the barite (0 0 1) surface have been measured at 108 °C using hydrothermal atomic force microscopy (HAFM) at moderate supersaturation and as a function of the aqueous barium:sulfate ratio (r). Barite growth hillocks at r ∼ 1 were bounded by 〈 1 2 0 〉 steps, however at r 〈 1 2 0 〉 , and the [0 1 0] steps developed. At r > 1, steps roughened and rounded as the kink site density increased. Step velocities peaked at r = 1 and decreased roughly symmetrically as a function of r, indicating the attachment rates of barium and sulfate ions are similar under these conditions. We hypothesize that the differences in our observations at high and low r arise from differences in the attachment rate constants for the obtuse and acute 〈 1 2 0 〉 steps. Based on results at low r, the data suggests the attachment rate constant for barium ions is similar for obtuse and acute steps. Based on results at high r, the data suggests the attachment rate constant for sulfate is greater for obtuse steps than acute steps. Utilizing a step growth model developed by Stack and Grantham (2010) the experimental step velocities as a function of r were readily fit while attempts to fit the data using a model developed by Zhang and Nancollas (1998) were less successful.

Step velocities on the celestite (0 0 1) surface have been measured as a function of temperature (23–45 °C), saturation state ( S = 1.1–2.2), ionic strength ( I = 0.01, 0.06, and 0.1 M), and aqueous strontium:sulfate ratio ( r = 0.01–100) using atomic force microscopy (AFM). Celestite growth hillocks were flanked by [0 1 0]-aligned step edges, which are polar, and step edges vicinal to 〈1 2 0〉, which are non-polar. [0 1 0] step velocities increased with temperature and saturation state, however step velocities did not vary significantly with ionic strength. Step velocities were non-linear with saturation state, suggesting a change in mechanism at high S as compared with low S. At constant S , the step velocities were maximized at r = 1 and decreased significantly at extreme r , demonstrating the governing role of solute stoichiometry. We successfully fit the step velocity data as a function of r using the Stack and Grantham (2010) nucleation and propagation model. Based on the results as a function of ionic strength and r , the mechanism at low S is likely ion-by-ion attachment to the step with an activation energy of 75 (±10) kJ mol −1 . At high S the mechanism is a combination of the one at low S and possibly attachment of a neutral species such as an ion pair with an activation energy of 43 (±9) kJ mol −1 .

Force spectroscopy is used to investigate crude oil/brine/rock interactions at reservoir temperatures and pressures, up to 120 °C and 10 MPa, for the first time. A newly-developed, high pressure, high temperature atomic force microscope (HP/HT-AFM) is used in combination with newly-designed, crude-oil functionalized AFM probes compatible with these conditions. Our results show that both temperature and pressure have significant impact on adhesion forces, demonstrating the necessity of testing in this environment to obtain results that accurately reflect interactions at reservoir conditions. The HP/HT-AFM design introduced here also allows changing many other variables such as brine composition, dissolved gases, injection fluid additives, the type of crude oil, as well as the type of mineral surface. Consequently, the system introduced here has the capability to investigate interfacial interactions at reservoir conditions with unprecedented specificity, providing the basis for the development of optimized and tailored oil recovery techniques.

OBJECTIVES: Identify predictors of persistence with adalimumab (ADA) among veterans and privately insured patients with inflammatory bowel disease (IBD) in the United States. STUDY DESIGN: Retrospective cohort study. METHODS: Patients with IBD taking ADA as their first biologic were identified from the Veterans Health Administration (VHA) database from 2009 to 2013 and the Truven Health MarketScan database from 2009 to 2012 with a 12-month follow-up. Persistence was defined as continued use 1 year after initiation. Adherence was assessed by calculating a medication possession ratio, which was dichotomized as greater than 0.86 or less than or equal to 0.86. Multivariable logistic regression was used to evaluate predictors of persistence. RESULTS: There were 1030 patients in the VHA population compared with 3264 patients in the privately insured (MarketScan) cohort. In MarketScan, 1800 patients (55%) remained on ADA compared with 755 (73%) in the VHA cohort. In multivariable analysis, male sex (odds ratio [OR], 1.38; 95% CI, 1.16–1.63; P

The degree of hepatic lipid accumulation in obesity correlates with the severity of hyperinsulinemia and systemic insulin resistance. Here, we propose a mechanism that explains this associative link, whereby, hepatic steatosis dysregulates glucose and insulin homeostasis. Obesity-induced hepatocellular lipid accumulation results in hepatocyte depolarization. We have established that hepatocyte depolarization depresses hepatic afferent vagal nerve firing, increases GABA release from liver slices, and causes hyperinsulinemia. Preventing hepatic GABA release or eliminating the ability of the liver to communicate to the hepatic vagal nerve ameliorates the hyperinsulinemia and insulin resistance associated with diet-induced obesity. In people with obesity hepatic expression of GABA transporters is associated with glucose infusion and disposal rates during a hyperinsulinemic euglycemic clamp. Single nucleotide polymorphisms in hepatic GABA re-uptake transporters are associated with an increased incidence of type II diabetes mellitus. Herein, we identify GABA as a novel hepatokine that is dysregulated in obesity and whose release can be manipulated to mute or exacerbate the glucoregulatory dysfunction common to obesity.

Substandard and falsified medications are a major threat to public health, directly increasing the risk of treatment failure, antimicrobial resistance, morbidity, mortality and health expenditures. While antimalarial medicines are one of the most common to be of poor quality in low- and middle-income countries, their distributional impact has not been examined. This study assessed the health equity impact of substandard and falsified antimalarials among children under five in Uganda. Using a probabilistic agent-based model of paediatric malaria infection (Substandard and Falsified Antimalarial Research Impact, SAFARI model), we examine the present day distribution of the burden of poor-quality antimalarials by socio-economic status and urban/rural settings, and simulate supply chain, policy and patient education interventions. Patients incur US$26.1 million (7.8%) of the estimated total annual economic burden of substandard and falsified antimalarials, including $2.3 million (9.1%) in direct costs and $23.8 million (7.7%) in productivity losses due to early death. Poor-quality antimalarials annually cost $2.9 million to the government. The burden of the health and economic impact of malaria and poor-quality antimalarials predominantly rests on the poor (concentration index −0.28) and rural populations (98%). The number of deaths among the poorest wealth quintile due to substandard and falsified antimalarials was 12.7 times that of the wealthiest quintile, and the poor paid 12.1 times as much per person in out-of-pocket payments. Rural populations experienced 97.9% of the deaths due to poor-quality antimalarials, and paid 10.7 times as much annually in out-of-pocket expenses compared with urban populations. Our simulations demonstrated that interventions to improve medicine quality could have the greatest impact at reducing inequities, and improving adherence to antimalarials could have the largest economic impact. Substandard and falsified antimalarials have a significant health and economic impact, with greater burden of deaths, disability and costs on poor and rural populations, contributing to health inequities in Uganda.

Massive stars inject mechanical and radiative energy into the surrounding environment, which stirs it up, heats the gas, produces cloud and intercloud phases in the interstellar medium, and disrupts molecular clouds (the birth sites of new stars

ObjectiveEvaluate the feasibility and acceptability of routine aspirin in low-risk women, compared with screening-test indicated aspirin for the prevention of pre-eclampsia and fetal growth restriction.DesignMulticentre open-label feasibility randomised controlled trial.SettingTwo tertiary maternity hospitals in Dublin, Ireland.Participants546 low-risk nulliparous women completed the study.InterventionsWomen underwent computerised randomisation to: Group 1—routine aspirin 75 mg from 11 until 36 weeks; Group 2—no aspirin and; Group 3—aspirin based on the Fetal Medicine Foundation screening test.Primary and secondary outcome measures(1) Proportion agreeing to participate; (2) compliance with protocol; (3) proportion where first trimester uterine artery Doppler was obtainable and; (4) time taken to issue a screening result. Secondary outcomes included rates of pre-eclampsia and small-for-gestational-age fetuses.Results546 were included in the routine aspirin (n=179), no aspirin (n=183) and screen and treat (n=184) groups. 546 of 1054 were approached (51.8%) and enrolled. Average aspirin adherence was 90%. The uterine artery Doppler was obtained in 98.4% (181/184) and the average time to obtain a screening result was 7.6 (0–26) days. Of those taking aspirin, vaginal spotting was greater; n=29 (15.1%), non-aspirin n=28 (7.9%), OR 2.1 (95% CI 1.2 to 3.6). Postpartum haemorrhage >500 mL was also greater; aspirin n=26 (13.5%), no aspirin n=20 (5.6%), OR 2.6 (95% CI 1.4 to 4.8).ConclusionLow-risk nulliparous women are open to taking aspirin in pregnancy and had high levels of adherence. Aspirin use was associated with greater rates of vaginal bleeding. An appropriately powered randomised controlled trial is now required to address the efficacy and safety of universal low-dose aspirin in low-risk pregnancy compared with a screening approach.Trial registration numberISRCTN (15191778); Post-results.

To switch patients with ulcerative colitis (UC) from costlier 5-aminosalicylic acid compounds to sulfasalazine and assess (1) the cost savings, (2) the barriers to switching, and (3) adverse events (AEs) and adherence at 3 months after the drug switch.An open-label, pharmacist-administered drug switch program coordinated at an academic inflammatory bowel disease center.A clinical pharmacist contacted patients with UC who were prescreened by physicians and covered by specific insurers to enroll them in the drug switch program. Enrolled patients were followed for 3 months to assess AEs and medication adherence. Reasons for declining to participate were recorded.A total of 205 eligible patients were identified; only 14 enrolled, and 10 remained on sulfasalazine for the entire 3-month follow-up period. The enrollment rate was only 4.9%, yet a net cost savings of $22,828/3-month to the insurer was achieved (including program administration costs but excluding AE costs), with co-pays reduced by approximately $25 per month per patient. The rate of AEs on sulfasalazine (28.6%) was similar to that found in previous reports. Significant unanticipated barriers to switching were encountered, namely patient desire to not alter an existing effective drug regimen.A pharmacist-administered drug switch program in patients with UC was significantly more difficult than anticipated, with questionable achievement of cost savings. This experience suggests that future drug switches and studies should focus on patient preferences for drug switching, as this may have implications for switching from brand name to biosimilar drugs.

Produced waters are increasingly found to contain high levels of dissolved iron, with typical ferrous iron concentrations ranging from a few ppm to several hundred ppm. The presence of iron can cause issues in production, one problem being a detrimental effect on the performance of scale inhibitors. The aim of this work was to investigate scale inhibitor chemistries with improved iron tolerance, and apply a new product in the field to address a severe inorganic scale issue that had been encountered. Using static bottle tests to assess brine compatibility and anaerobic dynamic scale loop tests to assess scale inhibition efficiency, a wide variety of scale inhibitor chemistries containing different functional groups were screened. The aim was to identify an inhibitor which would give the best performance against calcium carbonate scale in the presence of up to 100ppm Fe2+. Previous studies have shown that the inhibition of calcium carbonate scale is more adversely affected by the presence of iron than the inhibition of barium sulfate scale, and as calcium carbonate was the main challenge in the field case the emphasis was placed on inhibiting this scale type. Initial compatibility studies revealed the additives with the best brine compatibility, and around nine additives were taken forward for performance testing. It was found that acrylic acid based copolymers demonstrated reasonable scale control at 5-20 ppm Fe2+, but at higher iron the high dose levels required meant that the limit of compatibility was reached before complete scale control had been achieved. The best performing additive for calcium carbonate was found to be a phosphonate derivative. A field trial was conducted in a predominantly calcium carbonate scaling environment as a proof of concept and scale inhibitor residuals were monitored over a 5-month period. After this successful study, further lab experiments were performed with the chosen inhibitor to demonstrate good calcium carbonate control in the presence of up to 100 ppm Fe2+. A comprehensive investigation of different scale inhibitor types resulted in an optimum chemistry to control calcium carbonate scale in the presence of high concentrations of ferrous iron. Applying this chemistry in the field has demonstrated better scale control than was being achieved with the previous scale inhibitor.

Background Global efforts to address the burden of malaria have stagnated in recent years with malaria cases beginning to rise. Substandard and falsified anti-malarial treatments contribute to this stagnation. Poor quality anti-malarials directly affect health outcomes by increasing malaria morbidity and mortality, as well as threaten the effectiveness of treatment by contributing to artemisinin resistance. Research to assess the scope and impact of poor quality anti-malarials is essential to raise awareness and allocate resources to improve the quality of treatment. A probabilistic agent-based model was developed to provide country-specific estimates of the health and economic impact of poor quality anti-malarials on paediatric malaria. This paper presents the methodology and case study of the Substandard and Falsified Antimalarial Research Impact (SAFARI) model developed and applied to Uganda. Results The total annual economic impact of malaria in Ugandan children under age five was estimated at US$614 million. Among children who sought medical care, the total economic impact was estimated at $403 million, including $57.7 million in direct costs. Substandard and falsified anti-malarials were a significant contributor to this annual burden, accounting for $31 million (8% of care-seeking children) in total economic impact involving $5.2 million in direct costs. Further, 9% of malaria deaths relating to cases seeking treatment were attributable to poor quality anti-malarials. In the event of widespread artemisinin resistance in Uganda, we simulated a 12% yearly increase in costs associated with paediatric malaria cases that sought care, inflicting $48.5 million in additional economic impact annually. Conclusions Improving the quality of treatment is essential to combat the burden of malaria and prevent the development of drug resistance. The SAFARI model provides country-specific estimates of the health and economic impact of substandard and falsified anti-malarials to inform governments, policy makers, donors and the malaria community about the threat posed by poor quality medicines. The model findings are useful to illustrate the significance of the issue and inform policy and interventions to improve medicinal quality. Electronic supplementary material The online version of this article (10.1186/s12936-018-2628-3) contains supplementary material, which is available to authorized users.

In municipal waste effluent treatment, ammonia removal by an inorganic cation exchanger is practiced in a few communities. However, cost is a major consideration by municipalities when it comes to applying new technologies. Some parts of the US, Southern California, for example, long faced with a deficit of good quality fresh water, have available a potential source in its once-used wastewater. An efficient, economical, and reliable demineralization process which can be adapted to the special problems encountered in wastewater treatment would eliminate one of the obstacles in the utilization of several million acre feet of wastewater being discharged annually to the oceans. Continuous countercurrent ion exchange has been successfully used for several pollution control applications. However, ion exchange also increases the total amount of solids in the regenerant waste streams. But for many applications and with the proper choice of regenerant chemicals, the concentrated waste stream can be recovered as a by-product.