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The research investigated the vegetative propagation of Bagoadlau (Xanthosthemon philippinensis Merr.) stem cuttings using different concentrations of indolebutyric acid (IBA). Pretreated cuttings were planted in polyethylene bags and observed in a fully covered chamber for 45 days. The study employed a single trial of completely randomized design (CRD) with five treatments (500 ppm, 100 ppm, 1,500 ppm, and 2000 ppm), each replicated four times. Results indicated significant variations among treatment means in terms of percent shooting, shoot length, percent rooting, number and length of adventitious roots, and percent callusing. Notably, 500 ppm and 1,500 ppm demonstrated the highest outcomes in percent shooting, shoot length, percent survival, measurement of adventitious roots, count of roots, and percentage of rooting. In contrast, the survival percentage of T2 (500 ppm) displayed the highest rate and consistent performance compared to other treatments. Hence, the study recommends using 500 ppm and 1,500 ppm for effective rooting of Bagoadlau (Xanthosthemon philippinensis Merr.) stem cuttings. The successful propagation of native species like Bagoadlau is particularly relevant to ecosystem restoration efforts in regions marked by land degradation and mining activities. The study addresses several crucial aspects by successfully establishing Bagoadlau on such lands. This includes the restoration of native biodiversity, improved soil, and water quality through stabilizing soil, preventing erosion, and acting as a natural filtration system.

The European Aerosol Research Lidar Network (EARLINET), part of the Aerosols, Clouds and Trace gases Research Infrastructure (ACTRIS), organized an intensive observational campaign in May 2020, with the objective of monitoring the atmospheric state over Europe during the COVID-19 lockdown and relaxation period. Besides the standard operational processing of the lidar data in EARLINET, for seven EARLINET sites having collocated sun-photometric observations in the Aerosol Robotic Network (AERONET), a network exercise was held in order to derive profiles of the concentration and effective column size distributions of the aerosols in the atmosphere, by applying the GRASP/GARRLiC (from Generalized Aerosol Retrieval from Radiometer and Lidar Combined data – GARRLiC – part of the Generalized Retrieval of Atmosphere and Surface Properties – GRASP) inversion algorithm. The objective of this network exercise was to explore the possibility of identifying the anthropogenic component and of monitoring its spatial and temporal characteristics in the COVID-19 lockdown and relaxation period. While the number of cases is far from being statistically significant so as to provide a conclusive description of the atmospheric aerosols over Europe during this period, this network exercise was fundamental to deriving a common methodology for applying GRASP/GARRLiC to a network of instruments with different characteristics. The limits of the approach are discussed, in particular the missing information close to the ground in the lidar measurements due to the instrument geometry and the sensitivity of the GRASP/GARRLiC retrieval to the settings used, especially for cases with low aerosol optical depth (AOD) like the ones we show here. We found that this sensitivity is well-characterized in the GRASP/GARRLiC products, since it is included in their retrieval uncertainties.

Abstract Background Risk-adjustment (RA) models are used to account for severity of illness in comparing patient outcomes across hospitals. Researchers specify covariates as main effects, but they often ignore interactions or use stratification to account for effect modification, despite limitations due to rare events and sparse data. Three Agency for Healthcare Research and Quality (AHRQ) hospital-level Quality Indicators currently use stratified models, but their variable performance and limited interpretability motivated the design of better models. Methods We analysed patient discharge de-identified data from 14 State Inpatient Databases, AHRQ Healthcare Cost and Utilization Project, California Department of Health Care Access and Information, and New York State Department of Health. We used hierarchical group lasso regularisation (HGLR) to identify first-order interactions in several AHRQ inpatient quality indicators (IQI) - IQI 09 (Pancreatic Resection Mortality Rate), IQI 11 (Abdominal Aortic Aneurysm Repair Mortality Rate), and Patient Safety Indicator 14 (Postoperative Wound Dehiscence Rate). These models were compared with stratum-specific and composite main effects models with covariates selected by least absolute shrinkage and selection operator (LASSO). Results HGLR identified clinically meaningful interactions for all models. Synergistic IQI 11 interactions, such as between hypertension and respiratory failure, suggest patients who merit special attention in perioperative care. Antagonistic IQI 11 interactions, such as between shock and chronic comorbidities, illustrate that naïve main effects models overestimate risk in key subpopulations. Interactions for PSI 14 suggest key subpopulations for whom the risk of wound dehiscence is similar between open and laparoscopic approaches, whereas laparoscopic approach is safer for other groups. Model performance was similar or superior for composite models with HGLR-selected features, compared to those with LASSO-selected features. Conclusions In this application to high-profile, high-stakes risk-adjustment models, HGLR selected interactions that maintained or improved model performance in populations with heterogeneous risk, while identifying clinically important interactions. The HGLR package is scalable to handle a large number of covariates and their interactions and is customisable to use multiple CPU cores to reduce analysis time. The HGLR method will allow scholars to avoid creating stratified models on sparse data, improve model calibration, and reduce bias. Future work involves testing using other combinations of risk factors, such as vital signs and laboratory values. Our study focuses on a real-world problem of considerable importance to hospitals and policy-makers who must use RA models for statutorily mandated public reporting and payment programmes.

Abstract Background Family-centered rounds is recognized as a best practice for hospitalized children, but it has only been possible for children whose families can physically be at the bedside during hospital rounds. The use of telehealth to bring a family member virtually to the child’s bedside during hospital rounds is a promising solution. We aim to evaluate the impact of virtual family-centered hospital rounds in the neonatal intensive care unit on parental and neonatal outcomes. Methods This two-arm cluster randomized controlled trial will randomize families of hospitalized infants to have the option to use telehealth for virtual hospital rounds (intervention) or usual care (control). The intervention-arm families will also have the option to participate in hospital rounds in-person or to not participate in hospital rounds. All eligible infants who are admitted to this single-site neonatal intensive care unit during the study period will be included. Eligibility requires that there be an English-proficient adult parent or guardian. We will measure participant-level outcome data to test the impact on family-centered rounds attendance, parent experience, family-centered care, parent activation, parent health-related quality of life, length of stay, breastmilk feeding, and neonatal growth. Additionally, we will conduct a mixed methods implementation evaluation using the RE-AIM (Reach, Effectiveness, Adoption, Implementation, Maintenance) framework. Discussion The findings from this trial will increase our understanding about virtual family-centered hospital rounds in the neonatal intensive care unit. The mixed methods implementation evaluation will enhance our understanding about the contextual factors that influence the implementation and rigorous evaluation of our intervention. Trial registration ClinicalTrials.gov Identifier: NCT05762835. Status: Not yet recruiting. First posted: March 10, 2023; last update posted: March 10, 2023.

Abstract Background Children presenting to emergency departments of community hospitals may require transfer to a children’s hospital for more definitive care, but the transfer process can be distressing and burdensome to patients, families, and the healthcare system. Using telehealth to bring the children’s hospital nurse virtually to the bedside of the child in the emergency department has the potential to promote family-centered care and minimize triage issues and other transfer-associated burdens. To explore the feasibility of the nurse-to-family telehealth intervention, we are conducting a pilot study. Methods This parallel cluster randomized controlled feasibility and pilot trial will randomize six community emergency departments to use either nurse-to-family telehealth (intervention) or usual care (control) for pediatric inter-facility transfers. All eligible children presenting to a participating site during the study period who require inter-facility transfer will be included. Eligibility requires that there be an English-speaking adult parent or guardian at the emergency department bedside. We will examine feasibility objectives that assess protocol assignment adherence, fidelity, and survey response rates. We will measure subject-level exploratory outcome data to test feasibility of data collection and to obtain effect size estimates; exploratory outcomes include family-centered care, family experience, parent acute stress, parent distress, and change in level of care. Additionally, we will conduct a mixed methods implementation evaluation using the RE-AIM (Reach, Effectiveness, Adoption, Implementation, Maintenance) framework. Discussion The findings from this trial will increase our understanding about nurse-to-family telehealth during pediatric transfers. The mixed methods implementation evaluation will provide relevant insight about the contextual factors that influence the implementation and rigorous evaluation of our intervention. Trial registration ClinicalTrials.gov Identifier: NCT05593900. First Posted: October 26, 2022. Last Update Posted: December 5, 2022.

The volume and composition of a thin layer of liquid covering the airway surface defend the lung from inhaled pathogens and debris. Airway epithelia secrete Cl– into the airway surface liquid through cystic fibrosis transmembrane conductance regulator (CFTR) channels, thereby increasing the volume of airway surface liquid. The discovery that pulmonary ionocytes contain high levels of CFTR led us to predict that ionocytes drive secretion. However, we found the opposite. Elevating ionocyte abundance increased liquid absorption, whereas reducing ionocyte abundance increased secretion. In contrast to other airway epithelial cells, ionocytes contained barttin/Cl– channels in their basolateral membrane. Disrupting barttin/Cl– channel function impaired liquid absorption, and overexpressing barttin/Cl– channels increased absorption. Together, apical CFTR and basolateral barttin/Cl– channels provide an electrically conductive pathway for Cl– flow through ionocytes, and the transepithelial voltage generated by apical Na+ channels drives absorption. These findings indicate that ionocytes mediate liquid absorption, and secretory cells mediate liquid secretion. Segregating these counteracting activities to distinct cell types enables epithelia to precisely control the airway surface. Moreover, the divergent role of CFTR in ionocytes and secretory cells suggests that cystic fibrosis disrupts both liquid secretion and absorption.

The purpose of this study is to investigate the ability of the Sentinel-5P TROPOspheric Monitoring Instrument (TROPOMI) to derive accurate geometrical features of lofted aerosol layers, selecting the Mediterranean Basin as the study area. Comparisons with ground-based correlative measurements constitute a key component in the validation of passive and active satellite aerosol products. For this purpose, we use ground-based observations from quality-controlled lidar stations reporting to the European Aerosol Research Lidar Network (EARLINET). An optimal methodology for validation purposes has been developed and applied using the EARLINET optical profiles and TROPOMI aerosol products, aiming at the in-depth evaluation of the TROPOMI aerosol layer height (ALH) product for the period 2018 to 2022 over the Mediterranean Basin. Seven EARLINET stations were chosen, taking into consideration their proximity to the sea, which provided 63 coincident aerosol cases for the satellite retrievals. In the following, we present the first validation results for the TROPOMI/S5P ALH using the optimized EARLINET lidar products employing the automated validation chain designed for this purpose. The quantitative validation at pixels over the selected EARLINET stations illustrates that the TROPOMI ALH product is consistent with the EARLINET lidar products, with a high correlation coefficient R=0.82 (R=0.51) and a mean bias of -0.51±0.77 km and -2.27±1.17 km over ocean and land, respectively. Overall, it appears that aerosol layer altitudes retrieved from TROPOMI are systematically lower than altitudes from the lidar retrievals. High-albedo scenes, as well as low-aerosol-load scenes, are the most challenging for the TROPOMI retrieval algorithm, and these results testify to the need to further investigate the underlying cause. This work provides a clear indication that the TROPOMI ALH product can under certain conditions achieve the required threshold accuracy and precision requirements of 1 km, especially when only ocean pixels are included in the comparison analysis. Furthermore, we describe and analyse three case studies in detail, one dust and two smoke episodes, in order to illustrate the strengths and limitations of the TROPOMI ALH product and demonstrate the presented validation methodology. The present analysis provides important additions to the existing validation studies that have been performed so far for the TROPOMI S5P ALH product, which were based only on satellite-to-satellite comparisons.

Objectives Overeating interventions and research often focus on single determinants and use subjective or nonpersonalized measures. We aim to (1) identify automatically detectable features that predict overeating and (2) build clusters of eating episodes that identify theoretically meaningful and clinically known problematic overeating behaviors (e.g., stress eating), as well as new phenotypes based on social and psychological features. Method Up to 60 adults with obesity in the Chicagoland area will be recruited for a 14-day free-living observational study. Participants will complete ecological momentary assessments and wear 3 sensors designed to capture features of overeating episodes (e.g., chews) that can be visually confirmed. Participants will also complete daily dietitian-administered 24-hour recalls of all food and beverages consumed. Analysis Overeating is defined as caloric consumption exceeding 1 standard deviation of an individual's mean consumption per eating episode. To identify features that predict overeating, we will apply 2 complementary machine learning methods: correlation-based feature selection and wrapper-based feature selection. We will then generate clusters of overeating types and assess how they align with clinically meaningful overeating phenotypes. Conclusions This study will be the first to assess characteristics of eating episodes in situ over a multiweek period with visual confirmation of eating behaviors. An additional strength of this study is the assessment of predictors of problematic eating during periods when individuals are not on a structured diet and/or engaged in a weight loss intervention. Our assessment of overeating episodes in real-world settings is likely to yield new insights regarding determinants of overeating that may translate into novel interventions.

Abstract Background Few interventions are known to reduce the incidence of respiratory failure that occurs following elective surgery (postoperative respiratory failure; PRF). We previously reported risk factors associated with PRF that occurs within the first 5 days after elective surgery (early PRF; E-PRF); however, PRF that occurs six or more days after elective surgery (late PRF; L-PRF) likely represents a different entity. We hypothesized that L-PRF would be associated with worse outcomes and different risk factors than E-PRF. Methods This was a retrospective matched case-control study of 59,073 consecutive adult patients admitted for elective non-cardiac and non-pulmonary surgical procedures at one of five University of California academic medical centers between October 2012 and September 2015. We identified patients with L-PRF, confirmed by surgeon and intensivist subject matter expert review, and matched them 1:1 to patients who did not develop PRF (No-PRF) based on hospital, age, and surgical procedure. We then analyzed risk factors and outcomes associated with L-PRF compared to E-PRF and No-PRF. Results Among 95 patients with L-PRF, 50.5% were female, 71.6% white, 27.4% Hispanic, and 53.7% Medicare recipients; the median age was 63 years (IQR 56, 70). Compared to 95 matched patients with No-PRF and 319 patients who developed E-PRF, L-PRF was associated with higher morbidity and mortality, longer hospital and intensive care unit length of stay, and increased costs. Compared to No-PRF, factors associated with L-PRF included: preexisiting neurologic disease (OR 4.36, 95% CI 1.81–10.46), anesthesia duration per hour (OR 1.22, 95% CI 1.04–1.44), and maximum intraoperative peak inspiratory pressure per cm H20 (OR 1.14, 95% CI 1.06–1.22). Conclusions We identified that pre-existing neurologic disease, longer duration of anesthesia, and greater maximum intraoperative peak inspiratory pressures were associated with respiratory failure that developed six or more days after elective surgery in adult patients (L-PRF). Interventions targeting these factors may be worthy of future evaluation.

Abstract ICD-11 provides a promising new way to capture healthcare-related harm or injury. In this paper, we elaborate on the framework for describing healthcare-related events where there is a presumed causal link between an event and underlying healthcare-related factors. The three-part model for describing healthcare-related harm or injury in ICD-11 consists of (1) a healthcare-related activity that is the cause of injury or other harm (selected from Chapter 23 of ICD-11); (2) a mode or mechanism of injury or harm, related to the underlying cause (also from Chapter 23 of ICD-11); and (3) the harmful consequences of the event to the patient, selected from any of Chapters 1 through 22 of ICD-11 (most importantly, the injury or harm experienced by the patient). Concepts from these three elements are linked/clustered through postcoordination to reflect the three-part model in a single coded expression. ICD-11 contains many novel features, and the three-part model described here for healthcare-related adverse events is a notable example.

A large uncertainty for the slow neutron capture nucleosynthesis (s-process) models is caused by the amount of neutrons available to the process itself. This quantity is strongly affected by the 13C(α,n)16O, and 22Ne(α,n)25Mg reaction cross sections, whose measurements at energies corresponding to the s-process thermal conditions (∼102 keV) are mainly hampered by the Coulomb barrier. For this reason, indirect approaches could offer a complementary way of investigation and, among these, the Trojan Horse Method (THM) has been applied to determine these cross sections overcoming the Coulomb barrier. With this approach, a low-energy binary reaction cross section can be obtained selecting the quasi-free contribution from a suitable three-body reaction cross section, taking advantage of the cluster structure of proper nuclei.

The 26Al abundance holds a special role in present-day astrophysics, since it is a probe of active nucleosynthesis in the Galaxy and a valuable constraint of Galactic core-collapse supernovae rate. It is estimated through the detection of the 1809-keV γ-line of the daughter 26Mg and from the superabundance of 26Mg in comparison with the most abundant 24Mg isotope in meteorites. Accurate knowledge of the reaction rates involving 26Al, its stable counterpart 27Al and 24Mg is then mandatory. Moreover, these nuclei enter the MgAl cycle playing an important role in the production of Al and Mg isotopes. Recently, high-resolution stellar surveys have shown that the Mg-Al anti-correlation in red giants of globular clusters may hide the existence of multiple stellar populations, and that the relative abundances of Mg isotopes may not show correlation with Al.The common thread running through these astrophysical scenarios is the 27Al(p,α)24Mg reaction, which is the main 27Al destruction channel and directly correlates its abundance with the 24Mg one. Since available reaction rates show an order of magnitude uncertainty owing to the vanishingly small cross section at astrophysical energies, we have applied the Trojan Horse Method to deduce the reaction rate with no need of extrapolation. The indirect measurement made it possible to assess the contribution of the 84-keV resonance and to lower the upper limits on the strength of nearby resonances, with potential important impact for astrophysics. In particular, modifications in the 27Al and 24Mg abundances up to ∼30% are predicted for intermediate mass stars.

Lipid droplets (LD) have long been considered as mere fat drops; however, LD have lately been revealed to be ubiquitous, dynamic and to be present in diverse organelles in which they have a wide range of key functions. Although incompletely understood, the biogenesis of eukaryotic LD initiates with the synthesis of neutral lipids (NL) by enzymes located in the endoplasmic reticulum (ER). The accumulation of NL leads to their segregation into nanometric nuclei which then grow into lenses between the ER leaflets as they are further filled with NL. The lipid composition and interfacial tensions of both ER and the lenses modulate their shape which, together with specific ER proteins, determine the proneness of LD to bud from the ER toward the cytoplasm. The most important function of LD is the buffering of energy. But far beyond this, LD are actively integrated into physiological processes, such as lipid metabolism, control of protein homeostasis, sequestration of toxic lipid metabolic intermediates, protection from stress, and proliferation of tumours. Besides, LD may serve as platforms for pathogen replication and defense. To accomplish these functions, from biogenesis to breakdown, eukaryotic LD have developed mechanisms to travel within the cytoplasm and to establish contact with other organelles. When nutrient deprivation occurs, LD undergo breakdown (lipolysis), which begins with the LD-associated members of the perilipins family PLIN2 and PLIN3 chaperone-mediated autophagy degradation (CMA), a specific type of autophagy that selectively degrades a subset of cytosolic proteins in lysosomes. Indeed, PLINs CMA degradation is a prerequisite for further true lipolysis, which occurs via cytosolic lipases or by lysosome luminal lipases when autophagosomes engulf portions of LD and target them to lysosomes. LD play a crucial role in several pathophysiological processes. Increased accumulation of LD in non-adipose cells is commonly observed in numerous infectious diseases caused by intracellular pathogens including viral, bacterial, and parasite infections, and is gradually recognized as a prominent characteristic in a variety of cancers. This review discusses current evidence related to the modulation of LD biogenesis and breakdown caused by intracellular pathogens and cancer.

This study was focused on investigating the biosorption of cadmium from aqueous solution by regional lignocellulosic wastes such as orange peel and rice husk. Sorbents were characterized by infrared spectroscopy and by determining the pH at the point zero charge. The materials were used in their natural form and modified with potassium hydroxide to analyze the sorption capacity of the contaminant. Removal levels were favoured by using the activated residues and by increasing the pH and dose of the biosorbent, while they decreased by increasing the cadmium concentration. For the systems evaluated, it was found that process equilibrium was quickly achieved, adjusting to a pseudo-second order kinetic. Finally, for orange peel a monolayer sorption would occur, while for rice peel the sites would be heterogeneous with different affinities to cadmium.

Aerosol particles are essential constituents of the Earth's atmosphere, impacting the earth radiation balance directly by scattering and absorbing solar radiation, and indirectly by acting as cloud condensation nuclei. In contrast to most greenhouse gases, aerosol particles have short atmospheric residence times, resulting in a highly heterogeneous distribution in space and time. There is a clear need to document this variability at regional scale through observations involving, in particular, the in situ near-surface segment of the atmospheric observation system. This paper will provide the widest effort so far to document variability of climate-relevant in situ aerosol properties (namely wavelength dependent particle light scattering and absorption coefficients, particle number concentration and particle number size distribution) from all sites connected to the Global Atmosphere Watch network. High-quality data from almost 90 stations worldwide have been collected and controlled for quality and are reported for a reference year in 2017, providing a very extended and robust view of the variability of these variables worldwide. The range of variability observed worldwide for light scattering and absorption coefficients, single-scattering albedo, and particle number concentration are presented together with preliminary information on their long-term trends and comparison with model simulation for the different stations. The scope of the present paper is also to provide the necessary suite of information, including data provision procedures, quality control and analysis, data policy, and usage of the ground-based aerosol measurement network. It delivers to users of the World Data Centre on Aerosol, the required confidence in data products in the form of a fully characterized value chain, including uncertainty estimation and requirements for contributing to the global climate monitoring system.

Background: Somatic cell score is an important parameter to predict milk quality and health of cows. However, in countries like Brazil, this trait is still not selected on a large scale, and no genetic parameters are reported in the literature. Objective: To estimate the variance components and genetic parameters for somatic cell score, milk yield, fat yield, protein yield, fat percentage, and protein percentage in Holstein cows. Methods: Records from 56,718 animals were used to estimate variance components, heritability, and genetic correlations using a multi-trait animal model by the REML method. Results: The heritability estimates were 0.19 for somatic cell score, 0.22 for milk yield, 0.26 for fat yield, 0.18 for protein yield, 0.61 for fat percentage, and 0.65 for protein percentage. The estimates of genetic correlations among analyzed traits ranged from -0.50 to 0.82. Conclusion: The low heritability observed for somatic cell score indicates that selection for this trait should result in benefits related to animal health and milk quality, but only in the long term. The low correlation between productive traits and somatic cell score indicates that inclusion of somatic cell score in animal breeding programs does not interfere negatively with the genetic selection for milk yield or solids.

Six months of stratospheric aerosol observations with the European Aerosol Research Lidar Network (EARLINET) from August 2017 to January 2018 are presented. The decay phase of an unprecedented, record-breaking stratospheric perturbation caused by wildfire smoke is reported and discussed in terms of geometrical, optical, and microphysical aerosol properties. Enormous amounts of smoke were injected into the upper troposphere and lower stratosphere over fire areas in western Canada on 12 August 2017 during strong thunderstorm–pyrocumulonimbus activity. The stratospheric fire plumes spread over the entire Northern Hemisphere in the following weeks and months. Twenty-eight European lidar stations from northern Norway to southern Portugal and the eastern Mediterranean monitored the strong stratospheric perturbation on a continental scale. The main smoke layer (over central, western, southern, and eastern Europe) was found at heights between 15 and 20 km since September 2017 (about 2 weeks after entering the stratosphere). Thin layers of smoke were detected at heights of up to 22–23 km. The stratospheric aerosol optical thickness at 532 nm decreased from values > 0.25 on 21–23 August 2017 to 0.005–0.03 until 5–10 September and was mainly 0.003–0.004 from October to December 2017 and thus was still significantly above the stratospheric background (0.001–0.002). Stratospheric particle extinction coefficients (532 nm) were as high as 50–200 Mm−1 until the beginning of September and on the order of 1 Mm−1 (0.5–5 Mm−1) from October 2017 until the end of January 2018. The corresponding layer mean particle mass concentration was on the order of 0.05–0.5 µg m−3 over these months. Soot particles (light-absorbing carbonaceous particles) are efficient ice-nucleating particles (INPs) at upper tropospheric (cirrus) temperatures and available to influence cirrus formation when entering the tropopause from above. We estimated INP concentrations of 50–500 L−1 until the first days in September and afterwards 5–50 L−1 until the end of the year 2017 in the lower stratosphere for typical cirrus formation temperatures of −55 ∘C and an ice supersaturation level of 1.15. The measured profiles of the particle linear depolarization ratio indicated a predominance of nonspherical smoke particles. The 532 nm depolarization ratio decreased slowly with time in the main smoke layer from values of 0.15–0.25 (August–September) to values of 0.05–0.10 (October–November) and < 0.05 (December–January). The decrease of the depolarization ratio is consistent with aging of the smoke particles, growing of a coating around the solid black carbon core (aggregates), and thus change of the shape towards a spherical form. We found ascending aerosol layer features over the most southern European stations, especially over the eastern Mediterranean at 32–35∘ N, that ascended from heights of about 18–19 to 22–23 km from the beginning of October to the beginning of December 2017 (about 2 km per month). We discuss several transport and lifting mechanisms that may have had an impact on the found aerosol layering structures.

OBJECTIVES/GOALS: Predictive models for health outcomes often have poor calibration potentially due to interactions that are ignored by standard methods. Using AHRQ models for Inpatient Quality Indicator (IQI) 11 Abdominal Aortic Aneurysm Repair and IQI 09 Pancreatic Resection mortality, we hypothesize that identifying interactions may improve model calibration. METHODS/STUDY POPULATION: We used adult discharge data from 16 states obtained from AHRQ Healthcare Cost and Utilization Project (State Inpatient Database), California Department of Health Care Access and Information, and New York State Department of Health. We used AHRQ’s v2021-1 Clinical Classifications Software Refined (CCSR) with present on admission flags to create features for risk-adjustment. We compared the performance of Least absolute shrinkage and selection operator (LASSO) model and first-order interaction models estimated using Hierarchical Group Lasso Regression (HGLR), after splitting the data into training and test sets. C-statistics, area under the precision-recall curve and Hosmer-Lemeshow calibration plots are reported. Finally, logistic regression models with selected CCSRs were evaluated on the test set. RESULTS/ANTICIPATED RESULTS: IQI 11 has four strata: open and endovascular repair of ruptured aneurysms (39% and 21% mortality, respectively); open and endovascular repair of unruptured aneurysms (6% and 0.8% mortality, respectively). IQI 09 has two strata: with and without pancreatic cancer (2% and 2.5% mortality, respectively). Comparing the HGLR model (with interaction effects) with Lasso models (without interactions), we noticed meaningful improvements in discrimination and calibration. However, for IQI 09, the extremely low mortality rate did not result in good HGLR or LASSO models. Interactions involving CCSRs could be identified using the novel HGLR method, which improved model performance given a heterogeneous population in IQI 11 with a mix of high and low event rates, unlike the more homogeneous patient population in IQI 09. DISCUSSION/SIGNIFICANCE: Standard implementations of regression models fail to address critical issues that arise in healthcare data – (a) quadratic explosion of potential interactions that cannot be manually identified, and (b) categorical variables with multiple levels or values (e.g., age categories). We propose innovative use of HGLR to robustly address these issues.

Abstract Identification of catastrophic events recorded as resedimented deep marine deposits can be challenging because of multiple possible triggering mechanisms. This study investigates seismo‐turbidites (STs) deposited in the Ionian Sea as a consequence of major historical earthquakes related to the Calabrian Arc subduction system. Taking advantage of the available sedimentological reconstructions, we focused our analysis on high‐resolution X‐ray fluorescence core scanner (XRF‐CS), organic carbon and isotopic data to define geochemical signatures characterizing the ST units. The relationships between geochemical and sedimentological proxies were statistically tested using Pearson correlation and principal component analysis (PCA). Up to ∼78% of the total variance in the data set can be reduced to three principal components which identified four elemental ratio groups associated to the degree of terrestrial/coastal influence in each major depositional unit (i.e., pelagic, ST sandy stacked units, homogenites, tsunamite‐seiche laminites, and tsunamite backwash). The sample score results were evaluated together with organic carbon data in order to assess geochemical variability throughout the composite turbidite structure in different basins settings. The basal parts of the ST contain coarse‐grained sediment stacks whose sources can be traced back and sedimentary processes (surficial sediment erosion/massive slope failures) can be defined using geochemical data. The topmost parts of the STs exhibit a mixed compositional character suggesting basin‐wide processes such as seiche oscillations and tsunami wave erosion/backwashing. The application of selected XRF‐CS based elemental ratios as proxies in paleoseismological studies can help reconstruct the seismic history of a continental margin.

Chagas disease is caused by infection with the protozoan parasite Trypanosoma cruzi (T. cruzi), an intracellular pathogen that causes significant morbidity and death among millions in the Americas from Canada to Argentina. Current therapy involves oral administration of the nitroimidazole benznidazole (BNZ), which has serious side effects that often necessitate cessation of treatment. To both avoid off-target side effects and reduce the necessary dosage of BNZ, we packaged the drug within poly(ethylene glycol)-block-poly(propylene sulfide) polymersomes (BNZ-PSs). We show that these vesicular nanocarriers enhanced intracellular delivery to phagocytic cells and tested this formulation in a mouse model of T. cruzi infection. BNZ-PS is not only nontoxic but also significantly more potent than free BNZ, effectively reducing parasitemia, intracellular infection, and tissue parasitosis at a 466-fold lower dose of BNZ. We conclude that BNZ-PS was superior to BNZ for treatment of T. cruzi infection in mice and that further modifications of this nanocarrier formulation could lead to a wide range of custom controlled delivery applications for improved treatment of Chagas disease in humans.

Light elements offer a unique opportunity for studying several astrophysical scenarios from Big Bang Nucleosynthesis to stellar physics. Understanding the stellar abundances of light elements is key to obtaining information on internal stellar structures and mixing phenomena in different evolutionary phases, such as the pre-main-sequence, main-sequence or red-giant branch. In such a case, light elements, i.e., lithium, beryllium and boron, are usually burnt at temperatures of the order of 2–5 × 106 K. Consequently, the astrophysical S(E)-factor and the reaction rate of the nuclear reactions responsible for the burning of such elements must be measured and evaluated at ultra-low energies (between 0 and 10 keV). The Trojan Horse Method (THM) is an experimental technique that allows us to perform this kind of measurements avoiding uncertainties due to the extrapolation and electron screening effects on direct data. A long Trojan Horse Method research program has been devoted to the measurement of light element burning cross sections at astrophysical energies. In addition, dedicated direct measurements have been performed using both in-beam spectroscopy and the activation technique. In this review we will report the details of these experimental measurements and the results in terms of S(E)-factor, reaction rate and electron screening potential. A comparison between astrophysical reaction rates evaluated here and the literature will also be given.

From the beginning of the third millennium a diversity of contexts related to the period between 1975 and 1983 were approached from the social sciences in general and from archeology in particular. From a case study in the province of Tucumán (Argentina), we present the technical and scientific contributions of an archeology of genocide involved with the processes of memory, truth and justice.

Submucosal glands (SMGs) are a prominent structure that lines human cartilaginous airways. Although it has been assumed that SMGs contribute to respiratory defense, that hypothesis has gone without a direct test. Therefore, we studied pigs, which have lungs like humans, and disrupted the gene for ectodysplasin (EDA-KO), which initiates SMG development. EDA-KO pigs lacked SMGs throughout the airways. Their airway surface liquid had a reduced ability to kill bacteria, consistent with SMG production of antimicrobials. In wild-type pigs, SMGs secrete mucus that emerges onto the airway surface as strands. Lack of SMGs and mucus strands disrupted mucociliary transport in EDA-KO pigs. Consequently, EDA-KO pigs failed to eradicate a bacterial challenge in lung regions normally populated by SMGs. These in vivo and ex vivo results indicate that SMGs are required for normal antimicrobial activity and mucociliary transport, two key host defenses that protect the lung.

The detection of the neutrinos produced in the p−p chain and in the CNO cycle can be used to test the Standard Solar Model. The 3He(α,γ)7Be reaction is the first reaction of the 2nd and 3rd branch of the p−p chain, therefore, the uncertainty of its cross section sensitively influences the prediction of the 7Be and 8B neutrino fluxes. Despite its importance and the large number of experimental and theoretical works devoted to this reaction, the knowledge on the reaction cross section at energies characterizing the core of the Sun (15 keV - 30 keV) is limited and further experimental efforts are needed to reach the desired (≈ 3%) accuracy. The precise knowledge on the external capture contribution to the 3He(α,γ)7Be reaction cross section is crucial for the theoretical description of the reaction mechanism. In the present work the indirect measurement of this external capture contribution using the Asymptotic Normalization Coefficient (ANC) technique is reported. To extract the ANC, the angular distributions of deuterons emitted in the 6Li(3He,d)7Be α-transfer reaction were measured with high precision at EH3e = 3.0 MeV and EH3e = 5.0 MeV. The ANCs were then extracted from comparison of DWBA calculations to the measured data and the zero energy astrophysical S-factor for 3He(α,γ)7Be reaction was found to be 0.534 ± 0.025 keVb.

Chagas disease, caused by the infection with the protozoan parasite Trypanosoma cruzi, is clinically manifested in approximately one-third of infected people by inflammatory heart disease (cardiomyopathy) and, to a minor degree, gastrointestinal tract disorders (megaesophagus or megacolon). Chagas disease is a zoonosis transmitted among animals and people through the contact with triatomine bugs, which are found in much of the western hemisphere, including most countries of North, Central and South America, between parallels 45° north (Minneapolis, USA) and south (Chubut Province, Argentina). Despite much research on drug discovery for T. cruzi, there remain only two related agents in widespread use. Likewise, treatment is not always indicated due to the serious side effects of these drugs. On the other hand, the epidemiology and pathogenesis of Chagas disease are both highly complex, and much is known about both. However, it is still impossible to predict what will happen in an individual person infected with T. cruzi, because of the highly variability of parasite virulence and human susceptibility to infection, with no definitive molecular predictors of outcome from either side of the host-parasite equation. In this Minireview we briefly discuss the current state of T. cruzi infection and prognosis and look forward to the day when it will be possible to employ precision health to predict disease outcome and determine whether and when treatment of infection may be necessary.

Targeted gene therapy strategies utilizing homology-driven repair (HDR) allow for greater control over transgene integration site, copy number, and expression—significant advantages over traditional vector-mediated gene therapy with random genome integration. However, the relatively low efficiency of HDR-based strategies limits their clinical application. Here, we used HDR to knock in a mutant dihydrofolate reductase (mDHFR) selection gene at the gene-edited CCR5 locus in primary human CD4+ T cells and selected for mDHFR-modified cells in the presence of methotrexate (MTX). Cells were transfected with CCR5-megaTAL nuclease mRNA and transduced with adeno-associated virus containing an mDHFR donor template flanked by CCR5 homology arms, leading to up to 40% targeted gene insertion. Clinically relevant concentrations of MTX led to a greater than 5-fold enrichment for mDHFR-modified cells, which maintained a diverse TCR repertoire over the course of expansion and drug selection. Our results demonstrate that mDHFR/MTX-based selection can be used to enrich for gene-modified T cells ex vivo, paving the way for analogous approaches to increase the percentage of HIV-resistant, autologous CD4+ T cells infused into HIV+ patients, and/or for in vivo selection of gene-edited T cells for the treatment of cancer. Keywords: gene editing, chemoselection, T cell gene therapy, lentiviral vectors, homology-directed repair, methotrexate, dihydrofolate reductase, adeno-associated viruses, HIV, cancer

Understanding subduction zone mechanics and resulting volcanism remains challenging. Here, the authors present seismic reflection profiles from the Mediterranean Sea where serpentinite diapirs are present on the external subduction system of the Calabrian Arc and may be linked to recent volcanism at Etna.

Spinocerebellar ataxia type 2 (SCA2) is an autosomal dominant neurodegenerative disease characterized by a progressive cerebellar syndrome, which can be isolated or associated with extracerebellar signs. It has been shown that patients affected by SCA2 present also cognitive impairments and psychiatric symptoms. The cerebellum is known to modulate cortical activity and to contribute to distinct functional networks related to higher-level functions beyond motor control. It is therefore conceivable that one or more networks, rather than isolated regions, may be dysfunctional in cerebellar degenerative diseases and that an abnormal connectivity within specific cerebello-cortical regions might explain the widespread deficits typically observed in patients. In the present study, the network-based statistics (NBS) approach was used to assess differences in functional connectivity between specific cerebellar and cerebral “nodes” in SCA2 patients. Altered inter-nodal connectivity was found between more posterior regions in the cerebellum and regions in the cerebral cortex clearly related to cognition and emotion. Furthermore, more anterior cerebellar lobules showed altered inter-nodal connectivity with motor and somatosensory cerebral regions. The present data suggest that in SCA2 a cerebellar dysfunction affects long-distance cerebral regions and that the clinical symptoms may be specifically related with connectivity changes between motor and non-motor cerebello-cortical nodes.

The human skin microbiota is quantitatively dominated by Gram-positive bacteria, detected by both culture and metagenomics. However, metagenomics revealed a huge variety of Gram-negative taxa generally considered from environmental origin. For species affiliation of bacteria in skin microbiota, clones of 16S rRNA gene and colonies growing on diverse culture media were analyzed. Species-level identification was achieved for 81% of both clones and colonies. Fifty species distributed in 26 genera were identified by culture, mostly belonging to Actinobacteria and Firmicutes, while 45 species-level operational taxonomic units distributed in 30 genera were detected by sequencing, with a high diversity of Proteobacteria. This mixed approach allowed the detection of 100% of the genera forming the known core skin Gram-negative microbiota and 43% of the known diversity of Gram-negative genera in human skin. The orphan genera represented 50% of the current skin pan-microbiota. Improved culture conditions allowed the isolation of Roseomonas mucosa, Aurantimonas altamirensis and Agrobacterium tumefaciens strains from healthy skin. For proteobacterial species previously described in the environment, we proposed the existence of skin-specific ecotypes, which might play a role in the fine-tuning of skin homeostasis and opportunistic infections but also act as a shuttle between environmental and human microbial communities. Therefore, skin-associated proteobacteria deserve to be considered in the One-Health concept connecting human health to the health of animals and the environment.

Lentiviral-mediated integration of a CFTR transgene cassette into airway basal cells is a strategy being considered for cystic fibrosis (CF) cell-based therapies. However, CFTR expression is highly regulated in differentiated airway cell types and a subset of intermediate basal cells destined to differentiate. Since basal stem cells typically do not express CFTR, suppressing the CFTR expression from the lentiviral vector in airway basal cells may be beneficial for maintaining their proliferative capacity and multipotency. We identified miR-106b as highly expressed in proliferating airway basal cells and extinguished in differentiated columnar cells. Herein, we developed lentiviral vectors with the miR-106b-target sequence (miRT) to both study miR-106b regulation during basal cell differentiation and detarget CFTR expression in basal cells. Given that miR-106b is expressed in the 293T cells used for viral production, obstacles of viral genome integrity and titers were overcome by creating a 293T-B2 cell line that inducibly expresses the RNAi suppressor B2 protein from flock house virus. While miR-106b vectors effectively detargeted reporter gene expression in proliferating basal cells and following differentiation in the air–liquid interface and organoid cultures, the CFTR-miRT vector produced significantly less CFTR-mediated current than the non-miR-targeted CFTR vector following transduction and differentiation of CF basal cells. These findings suggest that miR-106b is expressed in certain airway cell types that contribute to the majority of CFTR anion transport in airway epithelium.

Chagas disease is a life-threatening illness caused by the protozoan parasite Trypanosoma cruzi. One of the characteristics of chronic chagasic infection is the parasitic persistence in cardiac and smooth muscle tissues. For this reason etiologic treatment of Chagas disease in all phases of infection is highly recommended. Despite the high number of trypanocidal drugs that have been discovered in the last years, only two compounds, Benznidazole and Nifurtimox remain as the unique drugs approved for Chagas treatment. Far from ideal, these drugs display low sensitivity and specificity resulting in limited applications, mainly in the onset of the acute phase. Thus there is an urgent need to validate new anti- T. cruzi drugs that can be applied even in the cases of chronic patients, those who today have no safe and effective treatment available. This paper reviews the most important compounds that have been tested in clinical trials and the results obtained to date.

The Trojan Horse Method is an indirect method to measure reaction cross sections at energies of interest for nuclear astrophysics, exploiting the nuclei clustering properties. Here it is presented with its general features and detailed for the case of the 2H(d,p)3H and 2H(d,n)3He measurements, where interesting results for astrophysics and energy fusion power plants have been obtained.

Context: The Study Team integrates researchers of: National Association of Pharmacies (ANF); NHS Primary Care Unit USF S. Julião of Agrupamento dos Centros de Saúde (ACeS) Baixo Mondego; National Oncology Registry (IPO Lisboa); Faculty of Pharmacy University of Lisbon; and Skaggs School of Pharmacy University of Colorado. The trial involves primary care and local pharmacies vs. usual fragmented care. Population: USF patients ≥ 18 years on medication for hypertension and/or hyperlipidemia. Background There is some evidence of health outcomes improvements of certain public health services provided by pharmacists in collaborative environments with physicians. This research uses: care protocols as decision algorithms in the pharmacy dispensing software; exchange of information technology-driven between settings and with patients; interprofessional meetings between pharmacists, physicians and nurses (Quality Circles). The project is the first in Portugal with such innovative features. Methods The trial started in March 2016. Baseline data collection and recruitment started in April 2018. End of recruitment in November 2018. Patients are followed for at least 6 months: hypertension and/or hyperlipidemia management in collaborative care by pharmacies and primary care. Intervention package: (1) point-of-care measurements at pharmacy/USF; (2) cardiovascular risk assessment at pharmacy/USF; (3) medication management at pharmacy/USF; (4) lifestyle counselling at pharmacy/USF; (5) referral and request for medical appointment from pharmacy to USF via IT; (6) feedback from USF and follow-up at pharmacy; (7) refill text reminders from pharmacy to patient (MED180®); (8) Quality Circles; (9) reporting adverse events to the National Pharmacovigilance System. Three data sources: pharmacy dispensing software and primary care extraction files in all available data points; patient telephone questionnaires at baseline, 3, and 6 months. Descriptive statistics for baseline characteristics, follow-up assessments, process and outcomes. Changes in outcomes will use GLM models and difference-in-difference estimators. At the time of this abstract: 6 Quality Circles involving 27 pharmacists, 5 physicians and 5 nurses and 276 patients recruited in 20 intervention and control pharmacies. End of 6-month follow-up data collection is due in May 2019 (+2 months). Impact of change on outcomes Assessment of changes at 6 months on: - Primary out- comes (disease control): blood pressure; total cholesterol; proportion of controlled patients. - Secondary outcomes (health behaviors): other cardiovascular risk factors in hyperlipidemia patients 40-65 years old; medication adherence and persistence; proportion of adherent patients. - Exploratory outcomes: related use of healthcare resources (incl. hospitalization), medication profile incl. medication burden; and patient satisfaction with care. Quality of life, preferences and cost data collected alongside trial for a separate economic study. Lesson points We expect to: Assess the effectiveness, process and patient experience/satisfaction of this collaborative care pilot; Test the feasibility of collecting a standard set of indicators in real world patients; Pave the way for the technology-driven exchange of meaningful outcomes between pharmacies and primary care. Published in: ICHOM 2019 Conference, 2-3 May 2019, Rotterdam, Netherlands.

Background Worldwide community pharmacies are shifting their role in the healthcare system from simple medication dispensers to health care providers. High levels of satisfaction with pharmacy services were found in previous studies. This study has two main goals. The primary goal is to describe the levels of satisfaction and knowledge regarding pharmacy services in Portugal. The secondary goal is to explore the perceptions and the utilization of pharmacy services by the Portuguese. This statement includes exploring the impact of a set of variables on both perceptions and uses of pharmacies in regard to services that are currently offered as well as to new services that may be provided in the future. Methods A face-to-face survey of closed-ended questions was applied to a nationwide representative sample of the Portuguese population in September 2015. The sample was weighted based on population distribution across regions, habitat, age and gender. Data analysis comprises descriptive statistics and Multiple Correspondence Analysis to explore different typologies of respondent’s orientation toward community pharmacy. Results A total of 1114 interviews comprised the study. Of the respondents, 36% used the pharmacy as a first resource when seeking to treat a minor ailment, and 54% reported that they use the pharmacy as a first resource when seeking answers about medicines. Of those who visited their pharmacy at least once in the previous year, 94% were either globally satisfied or very satisfied. The level of acknowledgement of pharmacy services’ was also high among the Portuguese. Of the participants, 29% considered there could be more services available in pharmacies that are currently provided by other health care facilities. The construction of a typology of orientations towards community pharmacy practice resulted in three outcome groups: “Motivated” (63%), those with a connection to a pharmacy; “Settled” (23%), mainly those who had a pharmacy nearby; and “Demobilised” (14%), those who are weakly tied to a pharmacy. Conclusions The vast majority of the Portuguese population has a strong positive attitude towards their community pharmacy, as expressed by the high levels of satisfaction with, and positive evaluation of, the pharmacy’s services. Published in: BMC Health Serv Res. 2019;19:186.

Objective To conduct a systematic review of cost-effectiveness, cost-utility, and cost-benefit studies of DPP-4 inhibitors for diabetes treatment versus other antidiabetics. Methods Three investigators searched the CRD York, Tufts CEA Registry, and MEDLINE databases through 2015. We reviewed all potentially relevant titles and abstracts, and screened full-text articles, according to inclusion criteria. We established a quality score for each study based on a 35-item list. Results A total of 295 studies were identified, of which 20 were included. The average quality score was 0.720 on a 0–1 scale. All studies were performed in high- and middle-income countries, using a 3rd-party payer perspective and randomized clinical trials to measure effectiveness. Sitagliptin, saxagliptin and vildagliptin had an ICER below 25,000 €/QALY, as second-line and as add-ons to metformin, in comparison to sulfonylureas. When compared with sitagliptin, liraglutide (GLP-1 receptor agonist) had an ICER of up to 22,724 €/QALY for the 1.2-mg dosage, and up to 32,869 €/QALY for the 1.8-mg dosage. Insulin glargine was dominant when compared with sitagliptin. Conclusions According to the WHO threshold applied to the country and year of each study, DPP-4 inhibitors were highly cost-effective as second-line, as add-ons to metformin, in comparison with sulfonylureas. More recent therapies (GLP-1 receptor agonists and insulin glargine) were highly cost-effective in comparison to DPP-4 inhibitors. These results were obtained, however, on the basis of a limited number of studies, relying on the same few clinical trials, and financed by manufacturers. Further independent research is needed to confirm these findings. Published in: Eur J Health Econ. 2017;18:937-65.

BackgroundCoronary atherosclerosis raises the risk of acute myocardial infarction (AMI), and is usually included in AMI risk‐adjustment models. Percutaneous coronary intervention (PCI) does not cause atherosclerosis, but may contribute to the notation of atherosclerosis in administrative claims. We investigated how adjustment for atherosclerosis affects rankings of hospitals that perform PCI. Methods and ResultsThis was a retrospective cohort study of 414 715 Medicare beneficiaries hospitalized for AMI between 2009 and 2011. The outcome was 30‐day mortality. Regression models determined the association between patient characteristics and mortality. Rankings of the 100 largest PCI and non‐PCI hospitals were assessed with and without atherosclerosis adjustment. Patients admitted to PCI hospitals or receiving interventional cardiology more frequently had an atherosclerosis diagnosis. In adjustment models, atherosclerosis was associated, implausibly, with a 42% reduction in odds of mortality (odds ratio=0.58, P

Rosai-Dorfman disease (RDD) is a nonmalignant histiocytic disorder of unknown origin that is extremely rare. By immunohistochemistry, the RDD cells are characteristically S-100 positive and CD1a negative. Emperipolesis is a common histopathological finding, although not specific for RDD. Lymph node and cutaneous manifestations are most frequent, but diverse organs can be affected. The clinical course is unpredictable regardless of treatment. Here, we present a series of 8 cases presenting lymph node and/or cutaneous lesions. Lymph node involvement was seen in diverse regions, including mediastinal and retroperitoneal. The treatment response to steroids was diversified, and the chemotherapy response was disappointing. Associated autoimmune diseases (Sjögren syndrome and antiphospholipid syndrome) were observed in 2 patients. Regardless of therapy modality, these patients exhibited a favorable prognosis in a follow-up duration that ranged from 15 to 80 months.

Rosai-Dorfman disease (RDD) is a nonmalignant histiocytic disorder of unknown origin that is extremely rare. By immunohistochemistry, the RDD cells are characteristically S-100 positive and CD1a negative. Emperipolesis is a common histopathological finding, although not specific for RDD. Lymph node and cutaneous manifestations are most frequent, but diverse organs can be affected. The clinical course is unpredictable regardless of treatment. Here, we present a series of 8 cases presenting lymph node and/or cutaneous lesions. Lymph node involvement was seen in diverse regions, including mediastinal and retroperitoneal. The treatment response to steroids was diversified, and the chemotherapy response was disappointing. Associated autoimmune diseases (Sjögren syndrome and antiphospholipid syndrome) were observed in 2 patients. Regardless of therapy modality, these patients exhibited a favorable prognosis in a follow-up duration that ranged from 15 to 80 months.

BACKGROUND:Trypanosomatid parasites represent a major health issue affecting hundreds of million people worldwide, with clinical treatments that are partially effective and/or very toxic. They are responsible for serious human and plant diseases including Trypanosoma cruzi (Chagas disease), Trypanosoma brucei (Sleeping sickness), Leishmania spp. (Leishmaniasis), and Phytomonas spp. (phytoparasites). Both, animals and trypanosomatids lack the biosynthetic riboflavin (vitamin B2) pathway, the vital precursor of flavin mononucleotide (FMN) and flavin adenine dinucleotide (FAD) cofactors. While metazoans obtain riboflavin from the diet through RFVT/SLC52 transporters, the riboflavin transport mechanisms in trypanosomatids still remain unknown. METHODOLOGY/PRINCIPAL FINDINGS:Here, we show that riboflavin is imported with high affinity in Trypanosoma cruzi, Trypanosoma brucei, Leishmania (Leishmania) mexicana, Crithidia fasciculata and Phytomonas Jma using radiolabeled riboflavin transport assays. The vitamin is incorporated through a saturable carrier-mediated process. Effective competitive uptake occurs with riboflavin analogs roseoflavin, lumiflavin and lumichrome, and co-factor derivatives FMN and FAD. Moreover, important biological processes evaluated in T. cruzi (i.e. proliferation, metacyclogenesis and amastigote replication) are dependent on riboflavin availability. In addition, the riboflavin competitive analogs were found to interfere with parasite physiology on riboflavin-dependent processes. By means of bioinformatics analyses we identified a novel family of riboflavin transporters (RibJ) in trypanosomatids. Two RibJ members, TcRibJ and TbRibJ from T. cruzi and T. brucei respectively, were functionally characterized using homologous and/or heterologous expression systems. CONCLUSIONS/SIGNIFICANCE:The RibJ family represents the first riboflavin transporters found in protists and the third eukaryotic family known to date. The essentiality of riboflavin for trypanosomatids, and the structural/biochemical differences that RFVT/SLC52 and RibJ present, make the riboflavin transporter -and its downstream metabolism- a potential trypanocidal drug target.

Gamma-ray shielding and Cs immobilisation of high-density magnetite (MG) and iron powder (IP) in Portland cement (PC) based-S/S treatment of Cs – contaminated soils were investigated. Gamma ray spectrometer with High Purity Germanium (HPGe) detector was used for ??-ray emission measurement. Main results reveal that the replacement of PC by MG or IP (up to 50%) leads to a marked increase (up to about 4-fold) in the ??- ray shielding performance. A higher MG amount leads to a decrease that performance. The highest ??RS index of ~26% (662 keV) was found in the case of IP addition (33.3%). The use of MG-mixtures allows reaching slightly slower ??RS index jointly with the highest Cs-immobilisation of 97.8%. Results revealed MG - PC S/S as the best choice and could provide a basis for decision-making of S/S remediation of 137Cs-contaminated sites.

Multiple tissues and systems in the organism undergo modifications during aging due to an accumulation of damaged proteins, lipids, and genetic material. To counteract this process, the cells are equipped with specific mechanisms, such as autophagy and senescence. Particularly, the immune system undergoes a process called immunosenescence, giving rise to a chronic inflammatory status of the organism, with a decreased ability to counteract antigens. The obvious result of this process is a reduced defence capacity. Currently, there is evidence that some pathogens are able to accelerate the immunosenescence process for their own benefit. Although to date numerous reports show the autophagy–senescence relationship, or the connection between pathogens with autophagy or senescence, the link between the three actors remains unexplored. In this review, we have summarized current knowledge about important issues related to aging, senescence, and autophagy.

Abstract: The aim of the present study was to compare errors committed in the distribution of medicationsat a hospital pharmacy with those perceived by staff members involved in the distributionprocess. Medications distributed to the medical and surgical wards were analyzed. The drugswere dispensed in individualized doses per patient, separated by administration time in boxes orplastic bags for 24 hours of care and using the carbon copy of the prescription. Nineteen staffmembers involved in the drug-dispensing process were also interviewed. In the observationphase, 1963 drugs dispensed in 259 prescriptions were analyzed, with a total of 61 dispensingerrors (3.2% of the medications). The most frequent errors were omission of the prescribedmedication (23%) and distribution of non-prescribed medication (14.8%). In the interviews, themain errors perceived by the staff were medications dispensed at a concentration other thanthat prescribed (22%) and the distribution of non-prescribed medication or medication differentfrom that prescribed (20%). Differences were found between the most frequent errors observedand those reported by staff members. Nonetheless, the views of the staff proved coherent withthe literature on this issue. Keywords: medication errors, hospital medication system.

Abstract: The aim of the present study was to compare errors committed in the distribution of medicationsat a hospital pharmacy with those perceived by staff members involved in the distributionprocess. Medications distributed to the medical and surgical wards were analyzed. The drugswere dispensed in individualized doses per patient, separated by administration time in boxes orplastic bags for 24 hours of care and using the carbon copy of the prescription. Nineteen staffmembers involved in the drug-dispensing process were also interviewed. In the observationphase, 1963 drugs dispensed in 259 prescriptions were analyzed, with a total of 61 dispensingerrors (3.2% of the medications). The most frequent errors were omission of the prescribedmedication (23%) and distribution of non-prescribed medication (14.8%). In the interviews, themain errors perceived by the staff were medications dispensed at a concentration other thanthat prescribed (22%) and the distribution of non-prescribed medication or medication differentfrom that prescribed (20%). Differences were found between the most frequent errors observedand those reported by staff members. Nonetheless, the views of the staff proved coherent withthe literature on this issue.Keywords: medication errors, hospital medication system.

Se presentan los resultados de las prospecciones arqueológicas efectuadas en un sector de la quebrada del río Miriguaca, emplazada en la localidad de Antofagasta de la Sierra, en el NO de la provincia de Catamarca. Durante dichas investigaciones se relevaron una decena de asentamientos de ocupación prehispánica, además de un elevado número de bloques con representaciones rupestres de diferente cronología. En base a la presencia de un conjunto de elementos contextuales que se registraron asociados a los sitios: artefactos líticos, fragmentos cerámicos, representaciones rupestres y rasgos arquitectónicos de cronología conocida; conjuntamente con la obtención de una serie de fechados radiocarbónicos para algunos materiales procedentes de sondeos exploratorios realizados en los sitios, aportamos nueva información ocupacional regional, que involucra un amplio lapso temporal ( ca . 3600 a 700 años AP).

BackgroundThe National Quality Forum previously approved a quality indicator for mortality after congenital heart surgery developed by the Agency for Healthcare Research and Quality (AHRQ). Several parameters of the validated Risk Adjustment for Congenital Heart Surgery (RACHS‐1) method were included, but others differed. As part of the National Quality Forum endorsement maintenance process, developers were asked to harmonize the 2 methodologies. Methods and ResultsParameters that were identical between the 2 methods were retained. AHRQ's Healthcare Cost and Utilization Project State Inpatient Databases (SID) 2008 were used to select optimal parameters where differences existed, with a goal to maximize model performance and face validity. Inclusion criteria were not changed and included all discharges for patients

A naturally occurring 32-base pair deletion of the HIV-1 co-receptor CCR5 has demonstrated protection against HIV infection of human CD4+ T cells. Recent genetic engineering approaches using engineered nucleases to disrupt the gene and mimic this mutation show promise for HIV therapy. We developed a megaTAL nuclease targeting the third extracellular loop of CCR5 that we delivered to primary human T cells by mRNA transfection. The CCR5 megaTAL nuclease established resistance to HIV in cell lines and disrupted the expression of CCR5 on primary human CD4+ T cells with a high efficiency, achieving up to 80% modification of the locus in primary cells as measured by molecular analysis. Gene-modified cells engrafted at levels equivalent to unmodified cells when transplanted into immunodeficient mice. Furthermore, genetically modified CD4+ cells were preferentially expanded during HIV-1 infection in vivo in an immunodeficient mouse model. Our results demonstrate the feasibility of targeting CCR5 in primary T cells using an engineered megaTAL nuclease, and the potential to use gene-modified cells to reconstitute a patient's immune system and provide protection from HIV infection.

El eritema elevatum diutinum (EED) es una dermatosis crónica, poco frecuente, de causa desconocida, que al comienzo presenta histopatológicamente una vasculitis leucocitoclásticade la piel y luego evoluciona hacia una fibrosis. Presentamos una paciente con lesiones dermatológicas características y generalizadas de esta rara entidad, en la que se obtuvo una buena respuesta con la sulfonoterapia.Erythema Elevatum Diutinum (EED) is a rare chronic cutaneous condition of unknow origin, that initially presents histological as leucocytoclastic vasculitis of the skin and later resolves with fibrosis. We present a patient of this uncommon condition with typical cutaneous lesions and widespread involvement. The disease was initially misinterpreted on clinical examination. Dapsone therapy was followed by a remarkable recovery.

Two particles coincidences of identified 15C and unidentified particle from 9 13 Be C + collisions are analyzed as three particles exit channel 9 13 15 3 Be C C He (, ) α and 9 13 15 4 Be C C He (, ) τ . In spectrum of α −τ relative energy 7 Be well-known states with 7 ( ) E Be x = 4,7, 6,73 and 9,2 МeV are identified and other at 7 ( ) E Be x ~11,6, 13, (14,1), 15,7 and 18 MeV are also possible. Situation that states of 7 Be with 7 ( ) E Be x = 7,21 and ~ 10 МеВ are not observed in those reactions are explained their not α −τ cluster structure.