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PLOS ONE Alerts: New Articles



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Updated: 2018-04-23T00:27:03Z

 



(XML) Correction: Natal and breeding philopatry of female Steller sea lions in southeastern Alaska

2018-04-20T21:00:00Z

by Kelly K. Hastings, Lauri A. Jemison, Grey W. Pendleton, Kimberly L. Raum-Suryan, Kenneth W. Pitcher

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(XML) Prediction of soil organic carbon in a coal mining area by Vis-NIR spectroscopy

2018-04-20T21:00:00Z

by Wenjuan Sun, Xinju Li, Beibei Niu

Coal mining has led to increasingly serious land subsidence, and the reclamation of the subsided land has become a hot topic of concern for governments and scholars. Soil quality of reclaimed land is the key indicator to the evaluation of the reclamation effect; hence, rapid monitoring and evaluation of reclaimed land is of great significance. Visible-near infrared (Vis-NIR) spectroscopy has been shown to be a rapid, timely and efficient tool for the prediction of soil organic carbon (SOC). In this study, 104 soil samples were collected from the Baodian mining area of Shandong province. Vis-NIR reflectance spectra and soil organic carbon content were then measured under laboratory conditions. The spectral data were first denoised using the Savitzky-Golay (SG) convolution smoothing method or the multiple scattering correction (MSC) method, after which the spectral reflectance (R) was subjected to reciprocal, reciprocal logarithm and differential transformations to improve spectral sensitivity. Finally, regression models for estimating the SOC content by the spectral data were constructed using partial least squares regression (PLSR). The results showed that: (1) The SOC content in the mining area was generally low (at the below-average level) and exhibited great variability. (2) The spectral reflectance increased with the decrease of soil organic carbon content. In addition, the sensitivity of the spectrum to the change in SOC content, especially that in the near-infrared band of the original reflectance, decreased when the SOC content was low. (3) The modeling results performed best when the spectral reflectance was preprocessed by Savitzky-Golay (SG) smoothing coupled with multiple scattering correction (MSC) and first-order differential transformation (modeling R2 = 0.86, RMSE = 2.00 g/kg, verification R2 = 0.78, RMSE = 1.81 g/kg, and RPD = 2.69). In addition, the first-order differential of R combined with SG, MSC with R, SG together with MSC and R also produced better modeling results than other pretreatment combinations. Vis-NIR modeling with specific spectral preprocessing methods could predict SOC content effectively.(image)



(XML) Understanding the impact of the cofactor swapping of isocitrate dehydrogenase over the growth phenotype of Escherichia coli on acetate by using constraint-based modeling

2018-04-20T21:00:00Z

by Erick Armingol, Eduardo Tobar, Ricardo Cabrera

It has been proposed that NADP+-specificity of isocitrate dehydrogenase (ICDH) evolved as an adaptation of microorganisms to grow on acetate as the sole source of carbon and energy. In Escherichia coli, changing the cofactor specificity of ICDH from NADP+ to NAD+ (cofactor swapping) decreases the growth rate on acetate. However, the metabolic basis of this phenotype has not been analyzed. In this work, we used constraint-based modeling to investigate the effect of the cofactor swapping of ICDH in terms of energy production, response of alternative sources of NADPH, and partitioning of fluxes between ICDH and isocitrate lyase (ICL) -a crucial bifurcation when the bacterium grows on acetate-. We generated E. coli strains expressing NAD+-specific ICDH instead of the native enzyme, and bearing the deletion of the NADPH-producing transhydrogenase PntAB. We measured their growth rate and acetate uptake rate, modeled the distribution of metabolic fluxes by Flux Balance Analysis (FBA), and quantified the specific activities of NADPH-producing dehydrogenases in central pathways. The cofactor swapping of ICDH led to one-third decrease in biomass yield, irrespective of the presence of PntAB. According to our simulations, the diminution in growth rate observed upon cofactor swapping could be explained by one-half decrease in the total production of NADPH and a lower availability of carbon for biosynthesis because of a change in the partition at the isocitrate bifurcation. Together with an increased total ATP production, this scenario resulted in a 10-fold increment in the flux of ATP not used for growing purposes. PntAB was identified as the primary NADPH balancing response, with the dehydrogenases of the oxidative branch of the Pentose Phosphate Pathway and the malic enzyme playing a role in its absence. We propose that in the context of E. coli growing on acetate, the NADP+-specificity of ICDH is a trait that impacts not only NADPH production, but also the efficient allocation of carbon and energy.(image)



(XML) Provider reported barriers and solutions to improve testing among tuberculosis patients ‘eligible for drug susceptibility test’: A qualitative study from programmatic setting in India

2018-04-20T21:00:00Z

by Hemant Deepak Shewade, Arun M. Kokane, Akash Ranjan Singh, Malik Parmar, Manoj Verma, Prabha Desikan, Sheeba Naz Khan, Ajay M. V. Kumar

Background

In a study conducted in Bhopal district (a setting with facility for molecular drug susceptibility testing (DST)) located in central India in 2014–15, we found high levels of pre-diagnosis attrition among patients with presumptive multi drug-resistant tuberculosis (MDR-TB)–meaning TB patients who were eligible for DST, were not being tested.

Objectives

In this study, we explored the health care provider perspectives into barriers and suggested solutions for improving DST.

Methods

This was a descriptive qualitative study. One to one interviews (n = 10) and focus group discussions (n = 2) with experienced key informants involved in programmatic management of DR-TB were conducted in April 2017. Manual descriptive thematic analysis was performed.

Results

The key barriers reported were a) lack of or delay in identification of patients eligible for DST because of using treatment register as the source for identifying patients b) lack of assured specimen transport after patient identification and c) lack of tracking. Extra pulmonary TB patients were not getting identified as eligible for DST. Solutions suggested by the health care providers were i) generation of unique identifier at identification in designated microscopy center (DMC), immediate intimation of unique identifier to district and regular monitoring by senior TB laboratory and senior treatment supervisors of patients eligible for DST that were missed; ii) documentation of unique identifier at each step of cascade; iii) use of human carriers/couriers to transport specimen from DMCs especially in rural areas; and iv) routine entry of all presumptive extra-pulmonary TB specimen, as far as possible, in DMC laboratory register.

Conclusion

Lack of assured specimen transport and lack of accountability for tracking patient after identification and referral were the key barriers. The identification of patients eligible for DST among microbiologically confirmed TB at the time of diagnosis and among clinically confirmed TB at the time of treatment initiation is the key. Use of unique identifier at identification and its use to ensure cohort wise tracking has to be complemented with specimen transport support and prompt feedback to the DMC. The study has implications to improve detection of MDR-TB among diagnosed/notified TB patients.

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(XML) Modeling the dynamics and kinetics of HIV-1 Gag during viral assembly

2018-04-20T21:00:00Z

by Michael D. Tomasini, Daniel S. Johnson, Joshua S. Mincer, Sanford M. Simon

We report a computational model for the assembly of HIV-1 Gag into immature viral particles at the plasma membrane. To reproduce experimental structural and kinetic properties of assembly, a process occurring on the order of minutes, a coarse-grained representation consisting of a single particle per Gag molecule is developed. The model uses information relating the functional interfaces implicated in Gag assembly, results from cryo electron-tomography, and biophysical measurements from fluorescence microscopy, such as the dynamics of Gag assembly at single virions. These experimental constraints eliminated many classes of potential interactions, and narrowed the model to a single interaction scheme with two non-equivalent interfaces acting to form Gags into a hexamer, and a third interface acting to link hexamers together. This model was able to form into a hexameric structure with correct lattice spacing and reproduced biologically relevant growth rates. We explored the effect of genomic RNA seeding punctum growth, finding that RNA may be a factor in locally concentrating Gags to initiate assembly. The simulation results infer that completion of assembly cannot be governed simply by Gag binding kinetics. However the addition of membrane curvature suggests that budding of the virion from the plasma membrane could factor into slowing incorporation of Gag at an assembly site resulting in virions of the same size and number of Gag molecules independent of Gag concentration or the time taken to complete assembly. To corroborate the results of our simulation model, we developed an analytic model for Gag assembly finding good agreement with the simulation results.(image)



(XML) An incremental clustering method based on the boundary profile

2018-04-20T21:00:00Z

by Junpeng Bao, Wenqing Wang, Tianshe Yang, Guan Wu

Many important applications continuously generate data, such as financial transaction administration, satellite monitoring, network flow monitoring, and web information processing. The data mining results are always evolving with the newly generated data. Obviously, for the clustering task, it is better to incrementally update the new clustering results based on the old data rather than to recluster all of the data from scratch. The incremental clustering approach is an essential way to solve the problem of clustering with growing Big Data. This paper proposes a boundary-profile-based incremental clustering (BPIC) method to find arbitrarily shaped clusters with dynamically growing datasets. This method represents the existing clustering results with a collection of boundary profiles and discards the inner points of clusters rather than keep all data. It greatly saves both time and space storage costs. To identify the boundary profile, this paper presents a boundary-vector-based boundary point detection (BV-BPD) algorithm that summarizes the structure of the existing clusters. The BPIC method processes each new point in an online fashion and updates the clustering results in a batch mode. When a new point arrives, the BPIC method either immediately labels it or temporarily puts it into a bucket according to the relationship between the new data and the boundary profiles. A bucket is employed to distinguish the noise from the potential seeds of new clusters and alleviate the effects of data order. When the bucket is full, the BPIC method will cluster the data within it and update the clustering results. Thus, the BPIC method is insensitive to noise and the order of new data, which is critical for the robustness of the incremental clustering process. In the experiments, the performance of the boundary point detection algorithm BV-BPD is compared with the state-of-the-art method. The results show that the BV-BPD is better than the state-of-the-art method. Additionally, the performance of BPIC and other two incremental clustering methods are investigated in terms of clustering quality, time and space efficiency. The experimental results indicate that the BPIC method is able to get a qualified clustering result on a large dataset with higher time and space efficiency.(image)



(XML) Optimisation of three-dimensional lower jaw resection margin planning using a novel Black Bone magnetic resonance imaging protocol

2018-04-20T21:00:00Z

by Astrid M. Hoving, Joep Kraeima, Rutger H. Schepers, Hildebrand Dijkstra, Jan Hendrik Potze, Bart Dorgelo, Max J. H. Witjes

Background

MRI is the optimal method for sensitive detection of tumour tissue and pre-operative staging in oral cancer. When jawbone resections are necessary, the current standard of care for oral tumour surgery in our hospital is 3D virtual planning from CT data. 3D printed jawbone cutting guides are designed from the CT data. The tumour margins are difficult to visualise on CT, whereas they are clearly visible on MRI scans. The aim of this study was to change the conventional CT-based workflow by developing a method for 3D MRI-based lower jaw models. The MRI-based visualisation of the tumour aids in planning bone resection margins.

Materials and findings

A workflow for MRI-based 3D surgical planning with bone cutting guides was developed using a four-step approach. Key MRI parameters were defined (phase 1), followed by an application of selected Black Bone MRI sequences on healthy volunteers (phase 2). Three Black Bone MRI sequences were chosen for phase 3: standard, fat saturated, and an out of phase sequence. These protocols were validated by applying them on patients (n = 10) and comparison to corresponding CT data. The mean deviation values between the MRI- and the CT-based models were 0.63, 0.59 and 0.80 mm for the three evaluated Black Bone MRI sequences. Phase 4 entailed examination of the clinical value during surgery, using excellently fitting printed bone cutting guides designed from MRI-based lower jaw models, in two patients with oral cancer. The mean deviation of the resection planes was 2.3 mm, 3.8 mm for the fibula segments, and the mean axis deviation was the fibula segments of 1.9°.

Conclusions

This study offers a method for 3D virtual resection planning and surgery using cutting guides based solely on MRI imaging. Therefore, no additional CT data are required for 3D virtual planning in oral cancer surgery.

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(XML) Tracking the fate of adoptively transferred myeloid-derived suppressor cells in the primary breast tumor microenvironment

2018-04-20T21:00:00Z

by Jaclyn Sceneay, Christoph M. Griessinger, Sabrina H. L. Hoffmann, Shu Wen Wen, Christina S. F. Wong, Sophie Krumeich, Manfred Kneilling, Bernd J. Pichler, Andreas Möller

Myeloid-derived suppressor cells (MDSCs) are a heterogeneous population of immature myeloid progenitor cells that are expanded in cancer and act as potent suppressors of the anti-tumor immune response. MDSCs consist of two major subsets, namely monocytic (M-) MDSCs and granulocytic (G-) MDSCs that differ with respect to their phenotype, morphology and mechanisms of suppression. Here, we cultured bone marrow cells with IL-6 and GM-CSF in vitro to generate a population of bone marrow MDSCs (BM-MDSCs) similar to G-MDSCs from tumor-bearing mice in regards to phenotype, morphology and suppressive-function. Through fluorescent labeling of these BM-MDSCs and optical imaging, we could visualize the recruitment and localization of BM-MDSCs in breast tumor-bearing mice in vivo. Furthermore, we were able to demonstrate that BM-MDSCs home to primary and metastatic breast tumors, but have no significant effect on tumor growth or progression. Ex vivo flow cytometry characterization of BM-MDSCs after adoptive transfer demonstrated both organ-and tumor-specific effects on their phenotype and differentiation, demonstrating the importance of the local microenvironment on MDSC fate and function. In this study, we have developed a method to generate, visualize and detect BM-MDSCs in vivo and ex vivo through optical imaging and flow cytometry, in order to understand the organ-specific changes rendered to MDSCs in breast cancer.(image)



(XML) β1 integrins mediate the BMP2 dependent transcriptional control of osteoblast differentiation and osteogenesis

2018-04-20T21:00:00Z

by Molly Brunner, Noémie Mandier, Thierry Gautier, Genevieve Chevalier, Anne-Sophie Ribba, Philippe Guardiola, Marc R. Block, Daniel Bouvard

Osteoblast differentiation is a highly regulated process that requires coordinated information from both soluble factors and the extracellular matrix. Among these extracellular stimuli, chemical and physical properties of the matrix are sensed through cell surface receptors such as integrins and transmitted into the nucleus to drive specific gene expression. Here, we showed that the conditional deletion of β1 integrins in the osteo-precursor population severely impacts bone formation and homeostasis both in vivo and in vitro. Mutant mice displayed a severe bone deficit characterized by bone fragility and reduced bone mass. We showed that β1 integrins are required for proper BMP2 dependent signaling at the pre-osteoblastic stage, by positively modulating Smad1/5-dependent transcriptional activity at the nuclear level. The lack of β1 integrins results in a transcription modulation that relies on a cooperative defect with other transcription factors rather than a plain blunted BMP2 response. Our results point to a nuclear modulation of Smad1/5 transcriptional activity by β1 integrins, allowing a tight control of osteoblast differentiation.(image)



(XML) Anemia in tuberculosis cases and household controls from Tanzania: Contribution of disease, coinfections, and the role of hepcidin

2018-04-20T21:00:00Z

by Jerry Hella, Colin I. Cercamondi, Francis Mhimbira, Mohamed Sasamalo, Nicole Stoffel, Marcel Zwahlen, Thomas Bodmer, Sebastien Gagneux, Klaus Reither, Michael B. Zimmermann, Lorenz Risch, Lukas Fenner

Background

Tuberculosis (TB) induces a systemic inflammatory state affecting iron homeostasis. Patients with TB often have additional comorbidities such as anemia which can result in poorer treat outcomes. We studied the contribution of anemia and the role of the iron regulatory hormone hepcidin among TB patients and household contacts.

Methods

We analyzed serum samples from 102 TB cases and 98 controls without TB, matched by age/sex, for hepcidin, iron, and inflammation parameters. Five controls developed TB within 12 months. We used linear regression to assess associations.

Results

Anemia of chronic disease (ACD) was more frequent among cases than controls (59.8% vs. 26.1%), but iron-deficiency anemia more frequent in controls (10% vs. 1%). The median hepcidin level was higher in cases than controls (63.7 vs. 14.2 ng/mL), but coinfections with HIV, helminths, and respiratory pathogens did not show cumulative effects. Hepcidin was associated with more severe TB symptom scoring (coefficient 0.8, 95% confidence interval [CI] 0.5–1.2) and higher mycobacterial load (0.7, 95% CI 0.4–1.0). Hepcidin was higher in TB cases and controls who developed TB compared to controls without TB (p<0.001), even when restricting to HIV-negative study participants.

Conclusions

ACD was the predominate etiology in TB patients suggesting limited benefit from iron supplementation. Increased hepcidin levels long before active disease, indicating altered iron metabolism, may be a marker for developing disease among TB-exposed individuals. Clinical management of anemia and nutrition interventions in TB patients need to be considered to improve the clinical course and outcomes.

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(XML) Pulsatile operation of a continuous-flow right ventricular assist device (RVAD) to improve vascular pulsatility

2018-04-20T21:00:00Z

by Boon C. Ng, Matthias Kleinheyer, Peter A. Smith, Daniel Timms, William E. Cohn, Einly Lim

Despite the widespread acceptance of rotary blood pump (RBP) in clinical use over the past decades, the diminished flow pulsatility generated by a fixed speed RBP has been regarded as a potential factor that may lead to adverse events such as vasculature stiffening and hemorrhagic strokes. In this study, we investigate the feasibility of generating physiological pulse pressure in the pulmonary circulation by modulating the speed of a right ventricular assist device (RVAD) in a mock circulation loop. A rectangular pulse profile with predetermined pulse width has been implemented as the pump speed pattern with two different phase shifts (0% and 50%) with respect to the ventricular contraction. In addition, the performance of the speed modulation strategy has been assessed under different cardiovascular states, including variation in ventricular contractility and pulmonary arterial compliance. Our results indicated that the proposed pulse profile with optimised parameters (Apulse = 10000 rpm and ωmin = 3000 rpm) was able to generate pulmonary arterial pulse pressure within the physiological range (9–15 mmHg) while avoiding undesirable pump backflow under both co- and counter-pulsation modes. As compared to co-pulsation, stroke work was reduced by over 44% under counter-pulsation, suggesting that mechanical workload of the right ventricle can be efficiently mitigated through counter-pulsing the pump speed. Furthermore, our results showed that improved ventricular contractility could potentially lead to higher risk of ventricular suction and pump backflow, while stiffening of the pulmonary artery resulted in increased pulse pressure. In conclusion, the proposed speed modulation strategy produces pulsatile hemodynamics, which is more physiologic than continuous blood flow. The findings also provide valuable insight into the interaction between RVAD speed modulation and the pulmonary circulation under various cardiovascular states.(image)



(XML) Sweat glucose and GLUT2 expression in atopic dermatitis: Implication for clinical manifestation and treatment

2018-04-20T21:00:00Z

by Emi Ono, Hiroyuki Murota, Yuki Mori, Yoshichika Yoshioka, Yuko Nomura, Takichi Munetsugu, Hiroo Yokozeki, Ichiro Katayama

Sweat includes active components and metabolites, which are needed to maintain skin homeostasis. Component changes in sweat derived from atopic dermatitis (AD) have been reported. To investigate the influence of sweat components on the pathogenesis of AD, we performed a multifaceted assessment, including nuclear magnetic resonance spectroscopy-based metabolomic analysis, and linked these features to clinical features of AD. Distinctive properties of AD sweat are the quite-variation in protein, anti-microbial peptides and glucose concentrations. pH, sodium, and other salt levels in sweat of AD were comparable to that of healthy subjects. Sweat from AD patients with acute inflammation had a more prominent increase in glucose concentration than sweat from healthy individuals or those with AD with chronic inflammation. Topical glucose application delayed recovery of transepidermal water loss in barrier-disrupted mice. Furthermore, the glucose transporter GLUT2 was highly expressed in the lumen of sweat glands from AD patients. AD patients with chronic inflammation had significantly increased GLUT2 mRNA expression and near normal sweat glucose levels. Despite the small sample size in our study, we speculate that the increased glucose levels might be affected by AD severity and phenotype. We hope that this report will bring novel insight into the impact of sweat components on the clinical manifestation of AD.(image)



(XML) Catechol-O-Methyltransferase moderates effect of stress mindset on affect and cognition

2018-04-20T21:00:00Z

by Alia J. Crum, Modupe Akinola, Bradley P. Turnwald, Ted J. Kaptchuk, Kathryn T. Hall

There is evidence that altering stress mindset—the belief that stress is enhancing vs. debilitating—can change cognitive, affective and physiological responses to stress. However individual differences in responsiveness to stress mindset manipulations have not been explored. Given the previously established role of catecholamines in both placebo effects and stress, we hypothesized that genetic variation in catechol-O-methyltransferase (COMT), an enzyme that metabolizes catecholamines, would moderate responses to an intervention intended to alter participants’ mindsets about stress. Participants (N = 107) were exposed to a stress mindset manipulation (videos highlighting either the enhancing or debilitating effects of stress) prior to engaging in a Trier Social Stress task and subsequent cognitive tasks. The associations of the COMT rs4680 polymorphism with the effect of stress mindset video manipulations on cognitive and affective responses were examined. Genetic variation at rs4680 modified the effects of stress mindset on affective and cognitive responses to stress. Individuals homozygous for rs4680 low-activity allele (met/met) were responsive to the stress-is-enhancing mindset manipulation as indicated by greater increases in positive affect, improved cognitive functioning, and happiness bias in response to stress. Conversely, individuals homozygous for the high-activity allele (val/val) were not as responsive to the stress mindset manipulation. These results suggest that responses to stress mindset intervention may vary with COMT genotype. These findings contribute to the understanding of gene by environment interactions for mindset interventions and stress reactivity and therefore warrant further investigations.(image)



(XML) Type-2 diabetic aldehyde dehydrogenase 2 mutant mice (ALDH 2*2) exhibiting heart failure with preserved ejection fraction phenotype can be determined by exercise stress echocardiography

2018-04-20T21:00:00Z

by Guodong Pan, Srikar Munukutla, Ananya Kar, Joseph Gardinier, Rajarajan A. Thandavarayan, Suresh Selvaraj Palaniyandi

E487K point mutation of aldehyde dehydrogenase (ALDH) 2 (ALDH2*2) in East Asians intrinsically lowers ALDH2 activity. ALDH2*2 is associated with diabetic cardiomyopathy. Diabetic patients exhibit heart failure of preserved ejection fraction (HFpEF) i.e. while the systolic heart function is preserved in them, they may exhibit diastolic dysfunction, implying a jeopardized myocardial health. Currently, it is challenging to detect cardiac functional deterioration in diabetic mice. Stress echocardiography (echo) in the clinical set-up is a procedure used to measure cardiac reserve and impaired cardiac function in coronary artery diseases. Therefore, we hypothesized that high-fat diet fed type-2 diabetic ALDH2*2 mutant mice exhibit HFpEF which can be measured by cardiac echo stress test methodology. We induced type-2 diabetes in 12-week-old male C57BL/6 and ALDH2*2 mice through a high-fat diet. At the end of 4 months of DM induction, we measured the cardiac function in diabetic and control mice of C57BL/6 and ALDH2*2 genotypes by conscious echo. Subsequently, we imposed exercise stress by allowing the mice to run on the treadmill until exhaustion. Post-stress, we measured their cardiac function again. Only after treadmill running, but not at rest, we found a significant decrease in % fractional shortening and % ejection fraction in ALDH2*2 mice with diabetes compared to C57BL/6 diabetic mice as well as non-diabetic (control) ALDH2*2 mice. The diabetic ALDH2*2 mice also exhibited poor maximal running speed and distance. Our data suggest that high-fat fed diabetic ALDH2*2 mice exhibit HFpEF and treadmill exercise stress echo test is able to determine this HFpEF in the diabetic ALDH2*2 mice.(image)



(XML) A novel statistical method for assessing effective adherence to medication and calculating optimal drug dosages

2018-04-20T21:00:00Z

by Garrett Greene, Richard W. Costello, Breda Cushen, Imran Sulaiman, Elaine Mac Hale, Ronan M. Conroy, Frank Doyle

Objective

We derive a novel model-based metric for effective adherence to medication, and validate it using data from the INhaler Compliance Assessment device (INCATM). This technique employs dose timing data to estimate the threshold drug concentration needed to maintain optimal health.

Methods

The parameters of the model are optimised against patient outcome data using maximum likelihood methods. The model is fitted and validated by secondary analysis of two independent datasets from two remote-monitoring studies of adherence, conducted through clinical research centres of 5 Irish hospitals. Training data came from a cohort of asthma patients (~ 47,000 samples from 218 patients). Validation data is from a cohort of 204 patients with COPD recorded between 2014 and 2016.

Results

The time above threshold measure is strongly predictive of adverse events (exacerbations) in COPD patients (Odds Ratio of exacerbation = 0.52 per SD increase in adherence, 95% Confidence Interval [0.34–0.79]). This compares well with the best known previous method, the Area Under the dose-time Curve (AUC) (Odds Ratio = 0.69, 95% Confidence Interval [0.48–0.99]). In addition, the fitted value of the dose threshold (0.56 of prescribed dosage) suggests that prescribed doses may be unnecessarily high given good adherence.

Conclusions

The resulting metric accounts for missed doses, dose-timing errors, and errors in inhaler technique, and provides enhanced predictive validity in comparison to previously used measures. In addition, the method allows us to estimate the correct dosage required to achieve the effect of the medication using the patients’ own adherence data and outcomes. The adherence score does depend not on sex or other demographic factors suggesting that effective adherence is driven by individual behavioural factors.

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(XML) Combined intervention of swimming plus metformin ameliorates the insulin resistance and impaired lipid metabolism in murine gestational diabetes mellitus

2018-04-20T21:00:00Z

by Liping Huang, Pingping Yue, Xuefei Wu, Ting Yu, Yang Wang, Ji Zhou, Derun Kong, Keyang Chen

Gestational diabetes mellitus (GDM) has short- and long- term influence on pregnant women and fetus. Swimming, as an aerobic exercise, can effectively improve the blood glucose level in GDM, but the effect of mild swimming alone was not very substantial. Metformin, as an oral antidiabetic drug, has obvious hypoglycemic effect, and is economic also, but the long-term effect on pregnant women and fetus has not been completely clear. We hypothesize that combined intervention of mild swimming and low dose of metformin, may effectively reduce blood glucose, improve the pregnancy outcomes in GDM dams, but simultaneously avoiding the adverse effects caused by overdose of drug and impotence of mild swimming. The streptozotocin was used to stimulate C57BL/6J mice to develop GDM, by which serum glucose, TC, TG, LDL-C were increased significantly, meanwhile HDL-C was decreased significantly in the GDM control (DC) group compared with the normal control group. Swimming or metformin intervention slightly or moderately improves hyperglycemia, insulin sensitivity and lipid metabolism both in liver and skeletal muscle from GDM mice, while combined therapy of swimming plus metformin markedly ameliorated hyperglycemia (FPG, decreased by 22.2–59.5% from G10 to G18 versus DC group), insulin sensitivity (2.1 and 2.8 fold increase, respectively, in AKT activity versus DC group) and de novo lipogenesis (3.2 and 7.0 fold decrease, respectively, in ACC activity, and 1.94 and 5.1 fold decrease, respectively, in SREBP2 level, versus DC group) both in liver and skeletal muscle from GDM mice. We conclude that the combined intervention by metformin plus swimming may be more effective than single action to ameliorate glucose and lipid metabolism via improving insulin sensitivity in GDM mice.(image)



(XML) A haplotype of three SNPs in FTO had a strong association with body composition and BMI in Iranian male adolescents

2018-04-20T21:00:00Z

by Naser Kalantari, Nastaran Keshavarz Mohammadi, Pantea Izadi, Saeid Doaei, Maryam Gholamalizadeh, Hassan Eini-Zinab, Tuire Salonurmi, Shahram Rafieifar, Reza Janipoor, Ghasem Azizi Tabesh

Background

Single-nucleotide polymorphisms (SNPs), which are located in the first intron of the FTO gene, are reported to be associated with body weight and the body mass index (BMI). However, their effects on anthropometric measurements in adolescents are poorly understood.

Objective

This study aimed to investigate the association of three adjacent polymorphisms (rs9930506, rs9930501, & rs9932754) in the FTO gene with anthropometric indices in Iranian adolescent males.

Design

The participants comprised a total of 237 adolescent males who were recruited randomly from two high schools in Tehran, Iran. The DNA samples were genotyped for the FTO gene polymorphisms by DNA sequencing. BMI, body fat percentage (BF%), and body muscle percentage (BM%) were determined using a validated bioelectrical impedance analysis scale. The association of the FTO polymorphisms with weight, height, BMI, BF%, and BM% was investigated.

Results

A haplotype of rs9930506, rs9930501, and rs9932754 (GGT) in the first intron of the FTO with complete linkage disequilibrium (LD) was found to be significantly associated with higher weight (OR = 1.32), BMI (OR = 5.36) and BF% (OR = 1.46), and lower BM% (OR = 3.59) (all P<0.001). None of the students with GGC genotypes were underweight, while all of the students with AAT genotypes had high muscle mass.

Conclusions

A haplotype in the first intron of the FTO gene had a strong association with obesity indices in Iranian adolescent males. The FTO gene polymorphisms might have greater effects on anthropometric indices than what was previously imagined. Moreover, we suggested that the FTO gene exerted their effects on anthropometric measurements through haplotypes (and not single SNPs).

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(XML) How does food addiction influence dietary intake profile?

2018-04-20T21:00:00Z

by Aylin Ayaz, Reyhan Nergiz-Unal, Damla Dedebayraktar, Asli Akyol, A. Gulden Pekcan, Halit Tanju Besler, Zehra Buyuktuncer

This study aimed to investigate whether there was any difference in eating pattern, abnormal eating behaviour, obesity and the number of food addiction symptoms according to food addiction presence. A total sample of 851 healthy subjects living in Ankara (n = 360 male, n = 491 female) aged 19–65 years were included in this cross-sectional survey. Data on demographic information, 24-hour dietary recalls, Yale Food Addiction Scale (YFAS), Eating Attitudes Test-26 (EAT-26), and anthropometric measurements were collected through face-to-face interviews. Overall, 11.4% of participants were identified as “food addicted” (F: 13.0%; M: 9.2%). Subjects meeting criteria for ‘food addiction' had higher body mass index (35.1% were obese and 3.1% were underweight), compared to subjects without food addiction (13.1% were obese and 10.2% were underweight) (p<0.05). Abnormal eating attitudes estimated with EAT-26 were determined as 45.5% in males, 37.5% in females and 40.2% in total, among subjects with food addiction. Daily energy, protein and fat intakes were significantly higher in food addicted females, compared to non-addicted females (p<0.05). Participants with food addiction reported significantly more problems with foods, which contain high amounts of fat and sugar, compared to the participants without food addiction. Food addiction behaviour should be considered as a part of efforts towards reducing food related problems involving obesity.(image)



(XML) Impact of selected amino acids of HP0377 (Helicobacter pylori thiol oxidoreductase) on its functioning as a CcmG (cytochrome c maturation) protein and Dsb (disulfide bond) isomerase

2018-04-20T21:00:00Z

by Magdalena Joanna Grzeszczuk, Aleksandra Bąk, Anna Marta Banaś, Paweł Urbanowicz, Stanislaw Dunin-Horkawicz, Artur Gieldon, Cezary Czaplewski, Adam Liwo, Elżbieta K. Jagusztyn-Krynicka

Helicobacter pylori HP0377 is a thiol oxidoreductase, a member of the CcmG family involved in cytochrome biogenesis, as previously shown by in vitro experiments. In this report, we document that HP0377 also acts in vivo in the cytochrome assembly process in Bacillus subtilis, where it complements the lack of ResA. However, unlike other characterized proteins in this family, HP0377 is a dithiol reductase and isomerase. We elucidated how the amino acid composition of its active site modulates its functionality. We demonstrated that cis-proline (P156) is involved in its interaction with the redox partner (CcdA), as a P156T HP0377 variant is inactive in vivo and is present in the oxidized form in B. subtilis. Furthermore, we showed that engineering the HP0377 active motif by changing CSYC motif into CSYS or SSYC, clearly diminishes two activities (reduction and isomerization) of the protein. Whereas HP0377CSYA is inactive in reduction as well as in isomerization, HP0377CSYS retains reductive activity. Also, replacement of F95 by Q decreases its ability to regenerate scRNase and does not influence the reductive activity of HP0377CSYS towards apocytochrome c. HP0377 is also distinguished from other CcmGs as it forms a 2:1 complex with apocytochrome c. Phylogenetic analyses showed that, although HP0377 is capable of complementing ResA in Bacillus subtilis, its thioredoxin domain has a different origin, presumably common to DsbC.(image)



(XML) Plasma metabolomic biomarkers accurately classify acute mild traumatic brain injury from controls

2018-04-20T21:00:00Z

by Massimo S. Fiandaca, Mark Mapstone, Amin Mahmoodi, Thomas Gross, Fabio Macciardi, Amrita K. Cheema, Kian Merchant-Borna, Jeffrey Bazarian, Howard J. Federoff

Past and recent attempts at devising objective biomarkers for traumatic brain injury (TBI) in both blood and cerebrospinal fluid have focused on abundance measures of time-dependent proteins. Similar independent determinants would be most welcome in diagnosing the most common form of TBI, mild TBI (mTBI), which remains difficult to define and confirm based solely on clinical criteria. There are currently no consensus diagnostic measures that objectively define individuals as having sustained an acute mTBI. Plasma metabolomic analyses have recently evolved to offer an alternative to proteomic analyses, offering an orthogonal diagnostic measure to what is currently available. The purpose of this study was to determine whether a developed set of metabolomic biomarkers is able to objectively classify college athletes sustaining mTBI from non-injured teammates, within 6 hours of trauma and whether such a biomarker panel could be effectively applied to an independent cohort of TBI and control subjects. A 6-metabolite panel was developed from biomarkers that had their identities confirmed using tandem mass spectrometry (MS/MS) in our Athlete cohort. These biomarkers were defined at ≤6 hours following mTBI and objectively classified mTBI athletes from teammate controls, and provided similar classification of these groups at the 2, 3, and 7 days post-mTBI. The same 6-metabolite panel, when applied to a separate, independent cohort provided statistically similar results despite major differences between the two cohorts. Our confirmed plasma biomarker panel objectively classifies acute mTBI cases from controls within 6 hours of injury in our two independent cohorts. While encouraged by our initial results, we expect future studies to expand on these initial observations.(image)



(XML) Estimating plant distance in maize using Unmanned Aerial Vehicle (UAV)

2018-04-20T21:00:00Z

by Jinshui Zhang, Bruno Basso, Richard F. Price, Gregory Putman, Guanyuan Shuai

Distance between rows and plants are essential parameters that affect the final grain yield in row crops. This paper presents the results of research intended to develop a novel method to quantify the distance between maize plants at field scale using an Unmanned Aerial Vehicle (UAV). Using this method, we can recognize maize plants as objects and calculate the distance between plants. We initially developed our method by training an algorithm in an indoor facility with plastic corn plants. Then, the method was scaled up and tested in a farmer’s field with maize plant spacing that exhibited natural variation. The results of this study demonstrate that it is possible to precisely quantify the distance between maize plants. We found that accuracy of the measurement of the distance between maize plants depended on the height above ground level at which UAV imagery was taken. This study provides an innovative approach to quantify plant-to-plant variability and, thereby final crop yield estimates.(image)



(XML) Synergistic interaction between a PDE5 inhibitor (sildenafil) and a new adenosine A2A receptor agonist (LASSBio-1359) improves pulmonary hypertension in rats

2018-04-20T21:00:00Z

by Allan K. Alencar, Fábio I. Carvalho, Ananssa M. Silva, Sabrina T. Martinez, Jorge A. Calasans-Maia, Carlos M. Fraga, Eliezer J. Barreiro, Gisele Zapata-Sudo, Roberto T. Sudo

Introduction

Pulmonary hypertension (PH) is characterized by enhanced pulmonary vascular resistance, which causes right ventricle (RV) pressure overload and results in right sided heart failure and death. This work investigated the effectiveness of a combined therapy with PDE5 inhibitor (PDE5i) and a new adenosine A2A receptor (A2AR) agonist in mitigating monocrotaline (MCT) induced PH in rats.

Methods

An in vitro isobolographic analysis was performed to identify possible synergistic relaxation effect between sildenafil and LASSBio 1359 in rat pulmonary arteries (PAs). In the in vivo experiments, PH was induced in male Wistar rats by a single intraperitoneal injection of 60 mg/kg MCT. Rats were divided into the following groups: control (saline injection only), MCT + vehicle, MCT + sildenafil, MCT + LASSBio 1359 and MCT + combination of sildenafil and LASSBio 1359. Fourteen days after the MCT injection, rats were treated daily with oral administration of the regimen therapies or vehicle for 14 days. Cardiopulmonary system function and structure were evaluated by echocardiography. RV systolic pressure and PA endothelial function were measured.

Results

Isobolographic analysis showed a synergistic interaction between sildenafil and LASSBio 1359 in rat PAs. Combined therapy with sildenafil and LASSBio 1359 but not monotreatment with low dosages of either sildenafil or LASSBio 1359 ameliorated all of PH related abnormalities in cardiopulmonary function and structure in MCT challenged rats.

Conclusions

The combination of sildenafil and LASSBio 1359 has a synergistic interaction, suggesting that combined use of these pharmacological targets may be an alternative to improve quality of life and outcomes for PH patients.

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(XML) Empirical mode decomposition processing to improve multifocal-visual-evoked-potential signal analysis in multiple sclerosis

2018-04-20T21:00:00Z

by Luis de Santiago, Eva Sánchez-Morla, Román Blanco, Juan Manuel Miguel, Carlos Amo, Miguel Ortiz del Castillo, Almudena López, Luciano Boquete

Objective

To study the performance of multifocal-visual-evoked-potential (mfVEP) signals filtered using empirical mode decomposition (EMD) in discriminating, based on amplitude, between control and multiple sclerosis (MS) patient groups, and to reduce variability in interocular latency in control subjects.

Methods

MfVEP signals were obtained from controls, clinically definitive MS and MS-risk progression patients (radiologically isolated syndrome (RIS) and clinically isolated syndrome (CIS)). The conventional method of processing mfVEPs consists of using a 1–35 Hz bandpass frequency filter (XDFT).The EMD algorithm was used to decompose the XDFT signals into several intrinsic mode functions (IMFs). This signal processing was assessed by computing the amplitudes and latencies of the XDFT and IMF signals (XEMD). The amplitudes from the full visual field and from ring 5 (9.8–15° eccentricity) were studied. The discrimination index was calculated between controls and patients. Interocular latency values were computed from the XDFT and XEMD signals in a control database to study variability.

Results

Using the amplitude of the mfVEP signals filtered with EMD (XEMD) obtains higher discrimination index values than the conventional method when control, MS-risk progression (RIS and CIS) and MS subjects are studied. The lowest variability in interocular latency computations from the control patient database was obtained by comparing the XEMD signals with the XDFT signals. Even better results (amplitude discrimination and latency variability) were obtained in ring 5 (9.8–15° eccentricity of the visual field).

Conclusions

Filtering mfVEP signals using the EMD algorithm will result in better identification of subjects at risk of developing MS and better accuracy in latency studies. This could be applied to assess visual cortex activity in MS diagnosis and evolution studies.

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(XML) IFN-λ and microRNAs are important modulators of the pulmonary innate immune response against influenza A (H1N2) infection in pigs

2018-04-20T21:00:00Z

by Louise Brogaard, Lars E. Larsen, Peter M. H. Heegaard, Christian Anthon, Jan Gorodkin, Ralf Dürrwald, Kerstin Skovgaard

The innate immune system is paramount in the response to and clearance of influenza A virus (IAV) infection in non-immune individuals. Known factors include type I and III interferons and antiviral pathogen recognition receptors, and the cascades of antiviral and pro- and anti-inflammatory gene expression they induce. MicroRNAs (miRNAs) are increasingly recognized to participate in post-transcriptional modulation of these responses, but the temporal dynamics of how these players of the antiviral innate immune response collaborate to combat infection remain poorly characterized. We quantified the expression of miRNAs and protein coding genes in the lungs of pigs 1, 3, and 14 days after challenge with swine IAV (H1N2). Through RT-qPCR we observed a 400-fold relative increase in IFN-λ3 gene expression on day 1 after challenge, and a strong interferon-mediated antiviral response was observed on days 1 and 3 accompanied by up-regulation of genes related to the pro-inflammatory response and apoptosis. Using small RNA sequencing and qPCR validation we found 27 miRNAs that were differentially expressed after challenge, with the highest number of regulated miRNAs observed on day 3. In contrast, the number of protein coding genes found to be regulated due to IAV infection peaked on day 1. Pulmonary miRNAs may thus be aimed at fine-tuning the initial rapid inflammatory response after IAV infection. Specifically, we found five miRNAs (ssc-miR-15a, ssc-miR-18a, ssc-miR-21, ssc-miR-29b, and hsa-miR-590-3p)–four known porcine miRNAs and one novel porcine miRNA candidate–to be potential modulators of viral pathogen recognition and apoptosis. A total of 11 miRNAs remained differentially expressed 14 days after challenge, at which point the infection had cleared. In conclusion, the results suggested a role for miRNAs both during acute infection as well as later, with the potential to influence lung homeostasis and susceptibility to secondary infections in the lungs of pigs after IAV infection.(image)



(XML) Contrasting response of coexisting plant’s water-use patterns to experimental precipitation manipulation in an alpine grassland community of Qinghai Lake watershed, China

2018-04-20T21:00:00Z

by Huawu Wu, Jing Li, Xiao-Yan Li, Bin He, Jinzhao Liu, Zhiyun Jiang, Cicheng Zhang

Understanding species-specific changes in water-use patterns under recent climate scenarios is necessary to predict accurately the responses of seasonally dry ecosystems to future climate. In this study, we conducted a precipitation manipulation experiment to investigate the changes in water-use patterns of two coexisting species (Achnatherum splendens and Allium tanguticum) to alterations in soil water content (SWC) resulting from increased and decreased rainfall treatments. The results showed that the leaf water potential (Ψ) of A. splendens and A. tanguticum responded to changes in shallow and middle SWC at both the control and treatment plots. However, A. splendens proportionally extracted water from the shallow soil layer (0–10cm) when it was available but shifted to absorbing deep soil water (30–60 cm) during drought. By contrast, the A. tanguticum did not differ significantly in uptake depth between treatment and control plots but entirely depended on water from shallow soil layers. The flexible water-use patterns of A.splendens may be a key factor facilitating its dominance and it better acclimates the recent climate change in the alpine grassland community around Qinghai Lake.(image)



(XML) A colorimetric assay for vanillin detection by determination of the luminescence of o-toluidine condensates

2018-04-20T21:00:00Z

by Jin Zhao, Haixiong Xia, Tingyu Yu, Lu Jin, Xuehua Li, Yinghui Zhang, Liping Shu, Lingwen Zeng, Zhixu He

Vanillin (4-hydroxy-3-methoxybenzaldehyde), a food additive with rich milk flavor, is commonly used in the food, beverage and cosmetic industries. However, excessive consumption of vanillin may cause liver and kidney damage. Therefore, methods for detecting and controlling the level of vanillin in food, especially in infant powder, have important practical significance. In this study, we established a colorimetric assay for vanillin detection. The detection was performed under high-temperature and acidic conditions, which can induce the reaction of the aldehyde group of vanillin with the amino group of o-toluidine. The resulting product had a maximum absorption at 363 nm, which was quantified by a UV spectrophotometer. This assay had a limit of detection (LOD) of 1 pg mL−1 and a linear range between 1 μg mL−1 and 100 μg mL−1. The average recoveries at three spiked levels were in the range from 91.1% to 101.6% with a relative standard deviation (RSD) of 4.62% ~ 7.27%.(image)



(XML) Osteopontin plays a pivotal role in increasing severity of respiratory syncytial virus infection

2018-04-20T21:00:00Z

by Viviana Sampayo-Escobar, Ryan Green, Michael B. Cheung, Raminder Bedi, Subhra Mohapatra, Shyam S. Mohapatra

The molecular mechanisms underlying susceptibility to severe respiratory syncytial virus (RSV) infection remain poorly understood. Herein, we report on the role of osteopontin (OPN) in regulation of RSV infection in human epithelial cells and how interleukin-1 beta (IL-1β), a cytokine secreted soon after RSV infection, when persistently expressed can induce OPN expression leading to increased viral infection. We first compared OPN expression in two human epithelial cell lines: HEK-293 and HEp-2. In contrast to HEp-2, HEK-293 expresses low levels of pro-caspase-1 resulting in decreased IL-1β expression in response to RSV infection. We found a correlation between low IL-1β levels and a delay in induction of OPN expression in RSV-infected HEK-293 cells compared to HEp-2. This phenomenon could partially explain the high susceptibility of HEp-2 cells to RSV infection versus the moderate susceptibility of HEK-293 cells. Also, HEK-293 cells expressing low levels of pro-caspase-1 exhibit decreased IL-1β expression and delayed OPN expression in response to RSV infection. HEK-293 cells incubated with human rIL-1β showed a dose-dependent increase in OPN expression upon RSV infection. Also, incubation with rOPN increased RSV viral load. Moreover, HEp-2 cells or mice infected with a mucogenic RSV strain RSV-L19F showed elevated levels of OPN in contrast to mice infected with the laboratory RSV strain rA2. This correlated with elevated levels of OPN following infection with RSV-L19F compared to rA2. Together, these results demonstrate that increased OPN expression is regulated in part by IL-1β, and the interplay between IL-1β and OPN signaling may play a pivotal role in the spread of RSV infection.(image)



(XML) The association of adult height with the risk of cardiovascular disease and cancer in the population of Sardinia

2018-04-20T21:00:00Z

by Giovanni Mario Pes, Antonello Ganau, Eugenia Tognotti, Alessandra Errigo, Chiara Rocchi, Maria Pina Dore

The relationship between body height and the risk of non‒communicable diseases such as cardiovascular disease and cancer has been the subject of much debate in the epidemiological literature. Concerns have recently arisen over spurious associations due to confounding factors like birth cohort, especially in the context of epidemiological transition. The population of Sardinia represents an interesting case study, as the average physical stature of inhabitants was the lowest recorded in Europe until a few decades ago. In this population we tested whether height is an independent risk factor for cardiovascular disease and cancer. We analysed the stature of 10,427 patients undergoing endoscopy for any reason, for whom a detailed clinical history of cardiovascular disease and/or malignancies had been documented. Poisson regression modelling was used to test the association between stature and disease risk. When patients were subdivided according to sex and height tertiles, the risk of cardiovascular disease proved significantly greater for subjects in the lowest tertile irrespective of sex (men: 1.87; 95%CI 1.41‒2.47; women: 1.23; 95%CI 0.92‒1.66) and smaller for those in the highest tertile (men: 0.51; 95%CI 0.35‒0.75; women: 0.41; 95%CI 0.27‒0.61). However, after adjusting the risk for birth cohort and established risk factors, it mostly resulted in non-significant values, although the overall trend persisted. Similar results were obtained for all-cancer risk (relative risk for men and women in the lowest tertile: 1.44; 95%CI 1.09–1.90 and 1.17; 95%CI 0.93–1.48, in the highest tertile: 0.51; 95%CI 0.36–0.72 and 0.62; 95%CI 0.47–0.81, respectively) as well as for some of the most common types of cancer. We concluded that the risk of developing cardiovascular disease and malignancies does not vary significantly with stature in the Sardinian population, after adjusting for birth cohort and more obvious risk factors.(image)



(XML) The Dyad-Adaptive Paced Auditory Serial Addition Test (DA-PASAT): Normative data and the effects of repeated testing, simulated malingering, and traumatic brain injury

2018-04-20T21:00:00Z

by David L. Woods, John M. Wyma, Timothy J. Herron, E. William Yund, Bruce Reed

The Paced Auditory Serial Addition Test (PASAT) is widely used to evaluate processing speed and executive function in patients with multiple sclerosis, traumatic brain injury, and other neurological disorders. In the PASAT, subjects listen to sequences of digits while continuously reporting the sum of the last two digits presented. Four different stimulus onset asynchronies (SOAs) are usually tested, with difficulty increasing as SOAs are reduced. Ceiling effects are common at long SOAs, while the digit delivery rate often exceeds the subject’s processing capacity at short SOAs, causing some subjects to stop performing altogether. In addition, subjects may adopt an “alternate answer” strategy at short SOAs, which reduces the test’s demands on working-memory and processing speed. Consequently, studies have shown that the number of dyads (consecutive correct answers) is a more sensitive measure of PASAT performance than the overall number of correct sums. Here, we describe a 2.5-minute computerized test, the Dyad-Adaptive PASAT (DA-PASAT), where SOAs are adjusted with a 2:1 staircase, decreasing after each pair of correct responses and increasing after misses. Processing capacity is reflected in the minimum SOA (minSOA) achieved in 54 trials. Experiment 1 gathered normative data in two large populations: 1617 subjects in New Zealand ranging in age from 18 to 65 years, and 214 Californians ranging in age from 18 to 82 years. Minimum SOAs were influenced by age, education, and daily hours of computer-use. Minimum SOA z-scores, calculated after factoring out the influence of these factors, were virtually identical in the two control groups, as were response times (RTs) and dyad ratios (the proportion of hits occurring in dyads). Experiment 2 measured the test-retest reliability of the DA-PASAT in 44 young subjects who underwent three test sessions at weekly intervals. High intraclass correlation coefficients (ICCs) were found for minSOAs (0.87), response times (0.76), and dyad ratios (0.87). Performance improved across test sessions for all measures. Experiment 3 investigated the effects of simulated malingering in 50 subjects: 42% of simulated malingerers produced abnormal (p< 0.05) minSOA z-scores. Simulated malingerers with abnormal scores were distinguished with 87% sensitivity and 69% specificity from control subjects with abnormal scores by excessive differences between training performance and the actual test. Experiment 4 investigated patients with traumatic brain injury (TBI): patients with mild TBI performed within the normal range while patients with severe TBI showed deficits. The DA-PASAT reduces the time and stress of PASAT assessment while gathering sensitive measures of dyad processing that reveal the effects of aging, malingering, and traumatic brain injury on performance.(image)