158 results on '"Clark KM"'
Search Results
52. Tone series and the nature of working memory capacity development.
- Author
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Clark KM, Hardman KO, Schachtman TR, Saults JS, Glass BA, and Cowan N
- Subjects
- Adolescent, Adult, Child, Female, Humans, Intelligence, Male, Middle Aged, Music, Pattern Recognition, Physiological, Practice, Psychological, Psychological Tests, Psychology, Child, Auditory Perception, Memory, Short-Term
- Abstract
Recent advances in understanding visual working memory, the limited information held in mind for use in ongoing processing, are extended here to examine auditory working memory development. Research with arrays of visual objects has shown how to distinguish the capacity, in terms of the number of objects retained, from the precision of the object representations. We adapt the technique to sequences of nonmusical tones, in an investigation including children (6-13 years, N = 84) and adults (26-50 years, N = 31). For each series of 1 to 4 tones, the participant responded by using an 80-choice scale to try to reproduce the tone at a queried serial position. Despite the much longer-lasting usefulness of sensory memory for tones compared with visual objects, the observed tone capacity was similar to previous findings for visual capacity. The results also constrain theories of childhood working memory development, indicating increases with age in both the capacity and the precision of the tone representations, similar to the visual studies, rather than age differences in time-based memory decay. The findings, including patterns of correlations between capacity, precision, and some auxiliary tasks and questionnaires, establish capacity and precision as dissociable processes and place important constraints on various hypotheses of working memory development. (PsycINFO Database Record, ((c) 2018 APA, all rights reserved).)
- Published
- 2018
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53. How to deal with ground truthing affected by human-induced habitat change?: Identifying high-quality habitats for the Critically Endangered Red Siskin.
- Author
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Sánchez-Mercado A, Rodríguez-Clark KM, Miranda J, Ferrer-Paris JR, Coyle B, Toro S, Cardozo-Urdaneta A, and Braun MJ
- Abstract
Species distribution models (SDM) can be valuable for identifying key habitats for conservation management of threatened taxa, but anthropogenic habitat change can undermine SDM accuracy. We used data for the Red Siskin ( Spinus cucullatus ), a critically endangered bird and ground truthing to examine anthropogenic habitat change as a source of SDM inaccuracy. We aimed to estimate: (1) the Red Siskin's historic distribution in Venezuela; (2) the portion of this historic distribution lost to vegetation degradation; and (3) the location of key habitats or areas with both, a high probability of historic occurrence and a low probability of vegetation degradation. We ground-truthed 191 locations and used expert opinion as well as landscape characteristics to classify species' habitat suitability as excellent, good, acceptable, or poor. We fit a Random Forest model (RF) and Enhanced Vegetation Index (EVI) time series to evaluate the accuracy and precision of the expert categorization of habitat suitability. We estimated the probability of historic occurrence by fitting a MaxLike model using 88 presence records (1960-2013) and data on forest cover and aridity index. Of the entire study area, 23% (20,696 km
2 ) had a historic probability of Red Siskin occurrence over 0.743. Furthermore, 85% of ground-truthed locations had substantial reductions in mean EVI, resulting in key habitats totaling just 976 km2 , in small blocks in the western and central regions. Decline in Area of Occupancy over 15 years was between 40% and 95%, corresponding to an extinction risk category between Vulnerable and Critically Endangered. Relating key habitats with other landscape features revealed significant risks and opportunities for proposed conservation interventions, including the fact that ongoing vegetation degradation could limit the establishment of reintroduced populations in eastern areas, while the conservation of remaining key habitats on private lands could be improved with biodiversity-friendly agri- and silviculture programs.- Published
- 2017
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54. Reply.
- Author
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Clark KM, Li M, Shao J, and Lozoff B
- Subjects
- Food, Formulated, Humans, Infant Nutritional Physiological Phenomena, Breast Feeding, Iron
- Published
- 2017
- Full Text
- View/download PDF
55. Meaningful Activity for Long-Term Care Residents With Dementia: A Comparison of Activities and Raters.
- Author
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Mansbach WE, Mace RA, Clark KM, and Firth IM
- Subjects
- Aged, Female, Humans, Male, Outcome Assessment, Health Care, Program Evaluation, Social Participation psychology, Dementia psychology, Dementia rehabilitation, Homes for the Aged organization & administration, Long-Term Care psychology, Meaningful Use organization & administration, Nursing Homes organization & administration, Quality of Life, Recreation psychology
- Abstract
Purpose of the Study: Engagement in meaningful activities is associated with positive outcomes for persons with dementia, yet studies demonstrating quantitative evidence for which activities can be considered meaningful are lacking. We investigated MemPics™, a program designed to promote meaningful activity for individuals with dementia through engagement and cognitive stimulation. It was compared with other recreation activities offered in U.S. long-term care facilities to determine whether MemPics™ was rated as having more meaningful activity from both the perspectives of participants and recreation staff., Design and Methods: Long-term care residents with mild to moderate dementia that met eligibility criteria were randomly assigned to an activity group (treatment, control). Participants completed 2 sessions of either the experimental or control group activity with facility recreation staff. Both participants and staff rated each activity in terms of meaningfulness following each session., Results: Of the enrolled participants (N = 126), study analyses were based on the 94 participants (n = 48 treatment and n = 46 control; M age = 82.98±9.63) who completed the activity sessions. Compared to the control group activities, MemPics™ had significantly higher participant and staff ratings of meaningfulness. Scores between the 2 rater types were significantly different, with staff reporting higher meaningful activity than participants. Further support for MemPics™ was found in exit survey responses from participating staff., Implications: We discuss the merits and shortcoming of this study, the utility of MemPics™ for providing meaningful engagement in long-term care residents with mild to moderate dementia, and ideas for future research., (© The Author 2016. Published by Oxford University Press on behalf of The Gerontological Society of America. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)
- Published
- 2017
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56. The Citizen Nurse: An Educational Innovation for Change.
- Author
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Clark KM, Miller JP, Leuning C, and Baumgartner K
- Subjects
- Curriculum, Education, Nursing organization & administration, Humans, Nursing Education Research, Pilot Projects, Education, Nursing, Baccalaureate organization & administration, Interprofessional Relations, Organizational Innovation, Students, Nursing psychology
- Abstract
Background: Nursing education needs to provide the necessary tools for students to develop leadership skills and to practice civic agency to create meaningful change in the shifting health care field. This article focuses on facilitating a student's role in becoming a citizen nurse through curricular modifications., Method: Through an ongoing partnership, nursing faculty and community organizers implemented a year-long pilot project to discover the deeper insights into the role of a citizen nurse and to analyze the skills students need to be effective agents of change. Pilot lectures and workshops were held throughout the academic year, and curricular changes were implemented., Results: Based on input from pilot class experiences, student reflections, and faculty workshop feedback, the decision to implement ongoing curricular changes was made by the department., Conclusion: The development of citizen nurses in nursing education will pave the way for praxis embedded in meaningful work with just solutions, enhancing the agency of all involved in promoting health and well-being. [J Nurs Educ. 2017;56(4):247-250.]., (Copyright 2017, SLACK Incorporated.)
- Published
- 2017
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57. Breastfeeding, Mixed, or Formula Feeding at 9 Months of Age and the Prevalence of Iron Deficiency and Iron Deficiency Anemia in Two Cohorts of Infants in China.
- Author
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Clark KM, Li M, Zhu B, Liang F, Shao J, Zhang Y, Ji C, Zhao Z, Kaciroti N, and Lozoff B
- Subjects
- Anemia, Iron-Deficiency prevention & control, Breast Feeding adverse effects, China epidemiology, Cohort Studies, Confidence Intervals, Feeding Behavior, Female, Humans, Infant, Logistic Models, Male, Odds Ratio, Prevalence, Randomized Controlled Trials as Topic, Risk Assessment, Anemia, Iron-Deficiency epidemiology, Breast Feeding methods, Infant Formula, Iron blood
- Abstract
Objective: To assess associations between breastfeeding and iron status at 9 months of age in 2 samples of Chinese infants., Study Design: Associations between feeding at 9 months of age (breastfed as sole milk source, mixed fed, or formula fed) and iron deficiency anemia (IDA), iron deficiency, and iron sufficiency were determined in infants from Zhejiang (n = 142) and Hebei (n= 813) provinces. Iron deficiency was defined as body iron < 0 mg/kg, and IDA as iron deficiency + hemoglobin < 110 g/L. Multiple logistic regression assessed associations between feeding pattern and iron status., Results: Breastfeeding was associated with iron status (P < .001). In Zhejiang, 27.5% of breastfed infants had IDA compared with 0% of formula-fed infants. The odds of iron deficiency/IDA were increased in breastfed and mixed-fed infants compared with formula-fed infants: breastfed vs formula-fed OR, 28.8 (95% CI, 3.7-226.4) and mixed-fed vs formula-fed OR, 11.0 (95% CI, 1.2-103.2). In Hebei, 44.0% of breastfed infants had IDA compared with 2.8% of formula-fed infants. With covariable adjustment, odds of IDA were increased in breastfed and mixed-fed groups: breastfed vs formula-fed OR, 78.8 (95% CI, 27.2-228.1) and mixed-fed vs formula-fed OR, 21.0 (95% CI, 7.3-60.9)., Conclusions: In both cohorts, the odds of iron deficiency/IDA at 9 months of age were increased in breastfed and mixed-fed infants, and iron deficiency/IDA was common. Although the benefits of breastfeeding are indisputable, these findings add to the evidence that breastfeeding in later infancy identifies infants at risk for iron deficiency/IDA in many settings. Protocols for detecting and preventing iron deficiency/IDA in breastfed infants are needed., Trial Registration: ClinicalTrials.gov: NCT00642863 and NCT00613717., (Copyright © 2016 Elsevier Inc. All rights reserved.)
- Published
- 2017
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58. Dietary fat and physiological determinants of plasma chylomicron remnant homoeostasis in normolipidaemic subjects: insight into atherogenic risk.
- Author
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Irawati D, Mamo JC, Slivkoff-Clark KM, Soares MJ, and James AP
- Subjects
- Adult, Atherosclerosis blood, Chylomicrons blood, Cross-Over Studies, Dietary Fats blood, Fasting, Female, Homeostasis, Humans, Hyperlipidemias blood, Hyperlipidemias etiology, Male, Meals, Middle Aged, Palm Oil, Particle Size, Plant Oils administration & dosage, Plant Oils metabolism, Reference Values, Risk Factors, Apolipoprotein B-48 blood, Atherosclerosis etiology, Chylomicron Remnants blood, Dietary Fats administration & dosage, Lipid Metabolism physiology, Postprandial Period, Triglycerides blood
- Abstract
TAG depleted remnants of postprandial chylomicrons are a risk factor for atherosclerosis. Recent studies have demonstrated that in the fasted state, the majority of chylomicrons are small enough for transcytosis to arterial subendothelial space and accelerate atherogenesis. However, the size distribution of chylomicrons in the absorptive state is unclear. This study explored in normolipidaemic subjects the postprandial distribution of the chylomicron marker, apoB-48, in a TAG-rich lipoprotein plasma fraction (Svedberg flotation rate (Sf>400), in partially hydrolysed remnants (Sf 20-400) and in a TAG-deplete fraction (Sf<20), following ingestion of isoenergetic meals with either palm oil (PO), rice bran or coconut oil. Results from this study show that the majority of fasting chylomicrons are within the potentially pro-atherogenic Sf<20 fraction (70-75 %). Following the ingestion of test meals, chylomicronaemia was also principally distributed within the Sf<20 fraction. However, approximately 40 % of subjects demonstrated exaggerated postprandial lipaemia specifically in response to the SFA-rich PO meal, with a transient shift to more buoyant chylomicron fractions. The latter demonstrates that heterogeneity in the magnitude and duration of hyper-remnantaemia is dependent on both the nature of the meal fatty acids ingested and possible metabolic determinants that influence chylomicron metabolism. The study findings reiterate that fasting plasma TAG is a poor indicator of atherogenic chylomicron remnant homoeostasis and emphasises the merits of considering specifically, chylomicron remnant abundance and kinetics in the context of atherogenic risk. Few studies address the latter, despite the majority of life being spent in the postprandial and absorptive state.
- Published
- 2017
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59. Human CaaX protease ZMPSTE24 expressed in yeast: Structure and inhibition by HIV protease inhibitors.
- Author
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Clark KM, Jenkins JL, Fedoriw N, and Dumont ME
- Subjects
- Catalytic Domain, Humans, Membrane Proteins genetics, Membrane Proteins metabolism, Metalloendopeptidases genetics, Metalloendopeptidases metabolism, Recombinant Proteins chemistry, Recombinant Proteins genetics, Recombinant Proteins metabolism, Saccharomyces cerevisiae genetics, Saccharomyces cerevisiae metabolism, HIV Protease Inhibitors chemistry, Membrane Proteins antagonists & inhibitors, Membrane Proteins chemistry, Metalloendopeptidases antagonists & inhibitors, Metalloendopeptidases chemistry
- Abstract
The function and localization of proteins and peptides containing C-terminal "CaaX" (Cys-aliphatic-aliphatic-anything) sequence motifs are modulated by post-translational attachment of isoprenyl groups to the cysteine sulfhydryl, followed by proteolytic cleavage of the aaX amino acids. The zinc metalloprotease ZMPSTE24 is one of two enzymes known to catalyze this cleavage. The only identified target of mammalian ZMPSTE24 is prelamin A, the precursor to the nuclear scaffold protein lamin A. ZMPSTE24 also cleaves prelamin A at a second site 15 residues upstream from the CaaX site. Mutations in ZMPSTE24 result in premature-aging diseases and inhibition of ZMPSTE24 activity has been reported to be an off-target effect of HIV protease inhibitors. We report here the expression (in yeast), purification, and crystallization of human ZMPSTE24 allowing determination of the structure to 2.0 Å resolution. Compared to previous lower resolution structures, the enhanced resolution provides: (1) a detailed view of the active site of ZMPSTE24, including water coordinating the catalytic zinc; (2) enhanced visualization of fenestrations providing access from the exterior to the interior cavity of the protein; (3) a view of the C-terminus extending away from the main body of the protein; (4) localization of ordered lipid and detergent molecules at internal and external surfaces and also projecting through fenestrations; (5) identification of water molecules associated with the surface of the internal cavity. We also used a fluorogenic assay of the activity of purified ZMPSTE24 to demonstrate that HIV protease inhibitors directly inhibit the human enzyme in a manner indicative of a competitive mechanism., (© 2016 The Protein Society.)
- Published
- 2017
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60. Structure of the SLC4 transporter Bor1p in an inward-facing conformation.
- Author
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Coudray N, L Seyler S, Lasala R, Zhang Z, Clark KM, Dumont ME, Rohou A, Beckstein O, and Stokes DL
- Subjects
- Anion Exchange Protein 1, Erythrocyte ultrastructure, Structural Homology, Protein, Cryoelectron Microscopy methods, Fungal Proteins ultrastructure, Membrane Transport Proteins ultrastructure, Molecular Dynamics Simulation, Saccharomyces ultrastructure
- Abstract
Bor1p is a secondary transporter in yeast that is responsible for boron transport. Bor1p belongs to the SLC4 family which controls bicarbonate exchange and pH regulation in animals as well as borate uptake in plants. The SLC4 family is more distantly related to members of the Amino acid-Polyamine-organoCation (APC) superfamily, which includes well studied transporters such as LeuT, Mhp1, AdiC, vSGLT, UraA, SLC26Dg. Their mechanism generally involves relative movements of two domains: a core domain that binds substrate and a gate domain that in many cases mediates dimerization. To shed light on conformational changes governing transport by the SLC4 family, we grew helical membrane crystals of Bor1p from Saccharomyces mikatae and determined a structure at ∼6 Å resolution using cryo-electron microscopy. To evaluate the conformation of Bor1p in these crystals, a homology model was built based on the related anion exchanger from red blood cells (AE1). This homology model was fitted to the cryo-EM density map using the Molecular Dynamics (MD) Flexible Fitting method and then relaxed by all-atom MD simulation in explicit solvent and membrane. Mapping of water accessibility indicates that the resulting structure represents an inward-facing conformation. Comparisons of the resulting Bor1p model with the X-ray structure of AE1 in an outward-facing conformation, together with MD simulations of inward-facing and outward-facing Bor1p models, suggest rigid body movements of the core domain relative to the gate domain. These movements are consistent with the rocking-bundle transport mechanism described for other members of the APC superfamily., (© 2016 The Protein Society.)
- Published
- 2017
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61. The Efficacy of a Computer-Assisted Cognitive Rehabilitation Program for Patients with Mild Cognitive Deficits: A Pilot Study.
- Author
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Mansbach WE, Mace RA, and Clark KM
- Subjects
- Aged, Aged, 80 and over, Brief Psychiatric Rating Scale, Female, Humans, Male, Middle Aged, Pilot Projects, Cognition Disorders rehabilitation, Therapy, Computer-Assisted methods
- Abstract
Background/Study Context: Whereas computer-assisted cognitive rehabilitation (CR) programs show promise as tools for improving cognition in certain populations, there is not a consensus regarding their efficacy. This study focuses on restorative CR, a treatment designed to improve cognitive functioning affected by progressive brain changes due to disease or aging, through computer-assisted cognitive exercises. The purpose of this study was to investigate the efficacy of a computer-assisted restorative CR intervention for improving cognitive functioning in older rehabilitation patients with relatively mild cognitive deficits., Methods: Older adult residents in a Maryland retirement community (N = 43) who met inclusion criteria were assigned to either the CR treatment or the control group. Treatment group participants completed 3 weeks (nine sessions) of Memory Match, an online CR module designed to improve attention and visual memory, whereas the control group did not complete the CR program after the baseline assessment. Analyses were based on the 38 (n = 20 treatment, n = 18 control) participants (mean age = 78.08 ± 10.31) who completed the post-assessment Brief Cognitive Assessment Tool (BCAT) and a self-rating inventory (SRI) of cognitive ability., Results: Treatment group participants who received the CR treatment obtained significantly higher BCAT scores (medium to large effect size) at post-assessment than control group participants over the same period. Additional evidence for the efficacy of the CR program was found by comparing responses on a SRI of cognitive ability between the two groups., Conclusion: The authors discuss the merits and shortcoming of this pilot study, the utility of the CR program for older rehabilitation patients with relatively mild cognitive deficits, and ideas for future research.
- Published
- 2017
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62. Probing the role of the backbone carbonyl interaction with the Cu A center in azurin by replacing the peptide bond with an ester linkage.
- Author
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Clark KM, Tian S, van der Donk WA, and Lu Y
- Subjects
- Azurin genetics, Models, Molecular, Protein Conformation, Protein Engineering, Azurin chemistry, Azurin metabolism, Esters chemistry, Peptides chemistry
- Abstract
The role of a backbone carbonyl interaction with an engineered Cu
A center in azurin was investigated by developing a method of synthesis and incorporation of a depsipeptide where one of the amide bonds in azurin is replaced by an ester bond using expressed protein ligation. Studies by electronic absorption and electron paramagnetic resonance spectroscopic techniques indicate that, while the substitution does not significantly alter the geometry of the site, it weakens the axial interaction to the CuA center and strengthens the Cu-Cu bond, as evidenced by the blue shift of the near-IR absorption that has been assigned to the Cu-Cu ψ → ψ* transition. Interestingly, the changes in the electronic structure from the replacement did not result in a change in the reduction potential of the CuA center, suggesting that the diamond core structure of Cu2 SCys2 is resistant to variations in axial interactions.- Published
- 2016
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63. Using spatial patterns in illegal wildlife uses to reveal connections between subsistence hunting and trade.
- Author
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Sánchez-Mercado A, Asmüssen M, Rodríguez-Clark KM, Rodríguez JP, and Jedrzejewski W
- Subjects
- Animals, Birds, Humans, Reptiles, Rural Population, Urban Population, Animals, Wild, Commerce, Conservation of Natural Resources legislation & jurisprudence
- Abstract
Although most often considered independently, subsistence hunting, domestic trade, and international trade as components of illegal wildlife use (IWU) may be spatially correlated. Understanding how and where subsistence and commercial uses may co-occur has important implications for the design and implementation of effective conservation actions. We analyzed patterns in the joint geographical distribution of illegal commercial and subsistence use of multiple wildlife species in Venezuela and evaluated whether available data were sufficient to provide accurate estimates of the magnitude, scope, and detectability of IWU. We compiled records of illegal subsistence hunting and trade from several sources and fitted a random-forest classification model to predict the spatial distribution of IWUs. From 1969 to 2014, 404 species and 8,340,921 specimens were involved in IWU, for a mean extraction rate of 185,354 individuals/year. Birds were the most speciose group involved (248 spp.), but reptiles had the highest extraction rates (126,414 individuals/year vs. 3,133 individuals/year for birds). Eighty-eight percent of international trade records spatially overlapped with domestic trade, especially in the north and along the coast but also in western inland areas. The distribution of domestic trade was broadly distributed along roads, suggesting that domestic trade does not depend on large markets in cities. Seventeen percent of domestic trade records overlapped with subsistence hunting, but the spatial distribution of this overlap covered a much larger area than between commercial uses. Domestic trade seems to respond to demand from rural more than urban communities. Our approach will be useful for understanding how IWU works at national scales in other parts of the world., (© 2016 Society for Conservation Biology.)
- Published
- 2016
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64. Identification of Homogentisate Dioxygenase as a Target for Vitamin E Biofortification in Oilseeds.
- Author
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Stacey MG, Cahoon RE, Nguyen HT, Cui Y, Sato S, Nguyen CT, Phoka N, Clark KM, Liang Y, Forrester J, Batek J, Do PT, Sleper DA, Clemente TE, Cahoon EB, and Stacey G
- Subjects
- 4-Hydroxyphenylpyruvate Dioxygenase antagonists & inhibitors, 4-Hydroxyphenylpyruvate Dioxygenase metabolism, Adaptation, Physiological drug effects, Arabidopsis genetics, Enzyme Inhibitors toxicity, Gene Deletion, Genome, Plant, Herbicides toxicity, Homogentisic Acid metabolism, Isoenzymes metabolism, Metabolic Networks and Pathways drug effects, Mutation genetics, Phenotype, Plant Cells drug effects, Plant Cells metabolism, Glycine max drug effects, Glycine max physiology, Biofortification, Homogentisate 1,2-Dioxygenase metabolism, Plant Oils metabolism, Seeds enzymology, Glycine max enzymology, Vitamin E metabolism
- Abstract
Soybean (Glycine max) is a major plant source of protein and oil and produces important secondary metabolites beneficial for human health. As a tool for gene function discovery and improvement of this important crop, a mutant population was generated using fast neutron irradiation. Visual screening of mutagenized seeds identified a mutant line, designated MO12, which produced brown seeds as opposed to the yellow seeds produced by the unmodified Williams 82 parental cultivar. Using forward genetic methods combined with comparative genome hybridization analysis, we were able to establish that deletion of the GmHGO1 gene is the genetic basis of the brown seeded phenotype exhibited by the MO12 mutant line. GmHGO1 encodes a homogentisate dioxygenase (HGO), which catalyzes the committed enzymatic step in homogentisate catabolism. This report describes to our knowledge the first functional characterization of a plant HGO gene, defects of which are linked to the human genetic disease alkaptonuria. We show that reduced homogentisate catabolism in a soybean HGO mutant is an effective strategy for enhancing the production of lipid-soluble antioxidants such as vitamin E, as well as tolerance to herbicides that target pathways associated with homogentisate metabolism. Furthermore, this work demonstrates the utility of fast neutron mutagenesis in identifying novel genes that contribute to soybean agronomic traits., (© 2016 American Society of Plant Biologists. All Rights Reserved.)
- Published
- 2016
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65. Predicting Off-Label Antipsychotic Medication Use in a Randomly Selected Nursing Home Sample Based on Resident and Facility Characteristics.
- Author
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Mansbach WE, Mace RA, Clark KM, Firth IM, and Breeden JK
- Subjects
- Aged, Aged, 80 and over, Female, Homes for the Aged, Humans, Male, Maryland, Antipsychotic Agents therapeutic use, Dementia drug therapy, Drug Utilization Review, Nursing Homes statistics & numerical data, Off-Label Use statistics & numerical data
- Abstract
Reducing off-label antipsychotic medication use for behavioral and psychological symptoms of dementia (BPSD) in nursing home residents has been a centerpiece of government regulation, but without insight into utilization differences based on resident and facility characteristics. To examine whether resident and facility characteristics can predict off-label antipsychotic medication treatment for BPSD, residents prescribed antipsychotic medication (N = 216) from 17 Maryland nursing facilities were randomly selected. Based on physician diagnoses, 59.7% of participants were taking off-label antipsychotic medications for BPSD. Hierarchical logistic regression results suggest that dementia level (indicated by Brief Cognitive Assessment Tool scores) and age, but not facility characteristics, significantly predict greater likelihood of using off-label antipsychotic medications for BPSD. Having moderate-severe dementia was associated with more than a four-fold increase in off-label antipsychotic medication use for BPSD. Off-label use of antipsychotic medications for BPSD remains high, especially for older nursing home residents with more severe dementia, indicating that more targeted reduction approaches are needed. [Res Gerontol Nurs. 2016; 9(6):257-266.]., (Copyright 2016, SLACK Incorporated.)
- Published
- 2016
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66. Plasma triglyceride and high density lipoprotein cholesterol are poor surrogate markers of pro-atherogenic chylomicron remnant homeostasis in subjects with the metabolic syndrome.
- Author
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Irawati D, Mamo JC, Dhaliwal SS, Soares MJ, Slivkoff-Clark KM, and James AP
- Abstract
Background: Subjects with metabolic syndrome (MetS) exhibit impaired lipoprotein metabolism and have an increased risk of cardiovascular disease. Although the risk is attributed primarily to the risk associated with individual components, it is also likely affected by other associated metabolic defects. Remnants of postprandial lipoproteins show potent atherogenicity in cell and animal models of insulin resistance and in pre-diabetic subjects with postprandial dyslipidemia. However, few studies have considered regulation of chylomicron remnant homeostasis in MetS per se. This study measured the plasma concentration in Caucasian men and women of small dense chylomicrons following fasting and explored associations with metabolic and anthropometric measures., Methods: A total of 215 Australian Caucasian participants (median age 62 years) were investigated. Of them, 40 participants were classified as having MetS. Apolipoprotein (apo) B-48, an exclusive marker of chylomicrons, metabolic markers and anthropometric measures were determined following an overnight fast., Results: The fasting apo B-48 concentration was 40 % higher in subjects with MetS than those without MetS. In all subjects, triglyceride (r = 0.445, P < 0.0005), non-HDL cholesterol (r = 0.28, P < 0.0005) and HDL cholesterol concentration (r = -0.272, P < 0.0005) were weakly associated with apo B-48 concentration. In subjects with MetS, the association of apo B-48 with triglyceride and non-HDL cholesterol was enhanced, but neither were robust markers of elevated apo B-48 in MetS (r = 0.618 and r = 0.595 respectively). There was no association between apo B-48 and HDL cholesterol in subjects with MetS., Conclusion: This study demonstrates a substantial accumulation of pro-atherogenic remnants in subjects with MetS. We have shown that in a Caucasian cohort, the fasting plasma concentration of triglyceride or HDL/non-HDL cholesterol serves as poor surrogate markers of atherogenic chylomicron remnants. These findings suggest that subjects with MetS exhibit a chronic defect in chylomicron metabolism that is likely to contribute to their increased CV risk.
- Published
- 2016
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67. Deducing the symmetry of helical assemblies: Applications to membrane proteins.
- Author
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Coudray N, Lasala R, Zhang Z, Clark KM, Dumont ME, and Stokes DL
- Subjects
- Cryoelectron Microscopy, Escherichia coli, Image Processing, Computer-Assisted, Imaging, Three-Dimensional, Membrane Proteins ultrastructure, Membrane Transport Proteins ultrastructure, Models, Molecular, Porins ultrastructure, Saccharomyces cerevisiae chemistry, Saccharomyces cerevisiae Proteins ultrastructure, Membrane Proteins chemistry, Membrane Transport Proteins chemistry, Porins chemistry, Protein Conformation, alpha-Helical, Saccharomyces cerevisiae Proteins chemistry
- Abstract
Helical reconstruction represents a convenient and powerful approach for structure determination of macromolecules that assemble into helical arrays. In the case of membrane proteins, formation of tubular crystals with helical symmetry represents an attractive alternative, especially when their small size precludes the use of single-particle analysis. An essential first step for helical reconstruction is to characterize the helical symmetry. This process is often daunting, due to the complexity of helical diffraction and to the low signal-to-noise ratio in images of individual assemblies. Furthermore, the large diameters of the tubular crystals produced by membrane proteins exacerbates the innate ambiguities that, if not resolved, will produce incorrect structures. In this report, we describe a set of tools that can be used to eliminate ambiguities and to validate the choice of symmetry. The first approach increases the signal-to-noise ratio along layer lines by incoherently summing data from multiple helical assemblies, thus producing several candidate indexing schemes. The second approach compares the layer lines from images with those from synthetic models built with the various candidate schemes. The third approach uses unit cell dimensions measured from collapsed tubes to distinguish between these candidate schemes. These approaches are illustrated with tubular crystals from a boron transporter from yeast, Bor1p, and a β-barrel channel from the outer membrane of E. coli, OmpF., (Copyright © 2016 Elsevier Inc. All rights reserved.)
- Published
- 2016
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68. Synthesis and Reactivity of Low-Coordinate Titanium Synthons Supported by a Reduced Redox-Active Ligand.
- Author
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Clark KM
- Abstract
To further explore the reactivity and redox capability of the bis-arylimino acenaphthylene ligand (BIAN) in early transition metal complexes, the coordinatively unsaturated titanium synthons, [(dpp-BAAN)Ti(R)2] ([dpp-BAAN](2-) = N,N'-bis(2,6-diisopropylphenylamido)acenaphthylene and R = O(t)Bu (2) or CH2C(CH3)3 (3)), in which the BAAN ligand is reduced by two electrons, were isolated in good yields via sterically induced radical elimination reactions. Addition of p-tolyl azide to complex 3 initiated reductive elimination of the neopentyl ligands to generate a putative imido species. The imido species was trapped by a second oxidative addition of chloride ligands to yield the titanium imido complex, [(dpp-BIAN)Ti[═N(4-C6H4Me)]Cl2 (4). These reactions demonstrate that the BAAN ligand can provide redox equivalents for enhanced reactivity that includes oxidative addition and reductive elimination at d(0) metal centers.
- Published
- 2016
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69. Pulsed resources at tundra breeding sites affect winter irruptions at temperate latitudes of a top predator, the snowy owl.
- Author
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Robillard A, Therrien JF, Gauthier G, Clark KM, and Bêty J
- Subjects
- Animals, Arctic Regions, Breeding, Seasons, Strigiformes, Tundra
- Abstract
Irruptive migration is mostly observed in species specialized on pulsed resources and is thought to be a response to unpredictable changes in food supply. We assessed two alternative hypotheses to explain the periodic winter irruptions of snowy owls Bubo scandiacus every 3-5 years in temperate North America: (a) the lack-of-food hypothesis, which states that a crash in small mammal abundance on the Arctic breeding grounds forces owls to move out of the tundra massively to search for food in winter; (b) the breeding-success hypothesis, which states that high abundance of tundra small mammals during the summer allows for high production of young, thus increasing the pool of migrants moving south the following winter. We modeled winter irruptions of snowy owls in relation to summer food resources and geographic location. Winter abundance of owls was obtained from citizen-based surveys from 1994 to 2011 and summer abundance of small mammals was collected in summer at two distant sites in Canada: Bylot Island, NU (eastern High Arctic) and Daring Lake, NWT (central Low Arctic). Winter owl abundance was positively related to prey abundance during the previous summer at both sites and tended to decrease from western to eastern temperate North America. Irruptive migration of snowy owls was therefore best explained by the breeding success hypothesis and was apparently caused by large-scale summer variations in food. Our results, combined with previous findings, suggest that the main determinants of irruptive migration may be species specific even in a guild of apparently similar species.
- Published
- 2016
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70. Iron deficiency (ID) at both birth and 9 months predicts right frontal EEG asymmetry in infancy.
- Author
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Armony-Sivan R, Zhu B, Clark KM, Richards B, Ji C, Kaciroti N, Shao J, and Lozoff B
- Subjects
- Electroencephalography, Female, Fetal Blood, Humans, Infant, Infant, Newborn, Male, Ferritins blood, Frontal Lobe physiopathology, Heme analysis, Iron Deficiencies, Protoporphyrins analysis
- Abstract
This study considered effects of timing and duration of iron deficiency (ID) on frontal EEG asymmetry in infancy. In healthy term Chinese infants, EEG was recorded at 9 months in three experimental conditions: baseline, peek-a-boo, and stranger approach. Eighty infants provided data for all conditions. Prenatal ID was defined as low cord ferritin or high ZPP/H. Postnatal ID was defined as ≥ two abnormal iron measures at 9 months. Study groups were pre- and postnatal ID, prenatal ID only, postnatal ID only, and not ID. GLM repeated measure analysis showed a main effect for iron group. The pre- and postnatal ID group had negative asymmetry scores, reflecting right frontal EEG asymmetry (mean ± SE: -.18 ± .07) versus prenatal ID only (.00 ± .04), postnatal ID only (.03 ± .04), and not ID (.02 ± .04). Thus, ID at both birth and 9 months was associated with right frontal EEG asymmetry, a neural correlate of behavioral withdrawal and negative emotions., Competing Interests: None of the authors had any personal or financial conflicts of interest., (© 2015 Wiley Periodicals, Inc.)
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- 2016
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71. Low-Dose Iron Supplementation in Infancy Modestly Increases Infant Iron Status at 9 Mo without Decreasing Growth or Increasing Illness in a Randomized Clinical Trial in Rural China.
- Author
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Lozoff B, Jiang Y, Li X, Zhou M, Richards B, Xu G, Clark KM, Liang F, Kaciroti N, Zhao G, Santos DC, Zhang Z, Tardif T, and Li M
- Subjects
- Anemia, Iron-Deficiency blood, Anemia, Iron-Deficiency drug therapy, Body Weight, China epidemiology, Dose-Response Relationship, Drug, Female, Ferritins blood, Hemoglobins metabolism, Humans, Infant, Iron Deficiencies, Iron, Dietary blood, Logistic Models, Male, Maternal Nutritional Physiological Phenomena, Nutritional Status, Pregnancy, Prevalence, Rural Population, Anemia, Iron-Deficiency epidemiology, Dietary Supplements, Infant Nutritional Physiological Phenomena, Iron, Dietary administration & dosage
- Abstract
Background: Previous trials of iron supplementation in infancy did not consider maternal iron supplementation., Objective: This study assessed effects of iron supplementation in infancy and/or pregnancy on infant iron status, illnesses, and growth at 9 mo., Methods: Enrollment occurred from December 2009 to June 2012 in Hebei, China. Infants born to women in a pregnancy iron supplementation trial were randomly assigned 1:1 to iron [∼1 mg Fe/(kg · d) as oral iron proteinsuccynilate] or placebo from 6 wk to 9 mo, excluding infants with cord ferritin <35 μg/L. Study groups were pregnancy placebo/infancy placebo (placebo/placebo), pregnancy placebo/infancy iron (placebo/iron), pregnancy iron/infancy placebo (iron/placebo), and pregnancy iron/infancy iron (iron/iron). The primary outcome was 9-mo iron status: iron deficiency (ID) by cutoff (≥2 abnormal iron measures) or body iron <0 mg/kg and ID + anemia (hemoglobin <110 g/L). Secondary outcomes were doctor visits or hospitalizations and weight or length gain from birth to 9 mo. Statistical analysis by intention to treat and dose-response (between number of iron bottles received and outcome) used logistic regression with concomitant RRs and general linear models, with covariate control as applicable., Results: Of 1482 infants randomly allocated, 1276 had 9-mo data (n = 312-327/group). Iron supplementation in infancy, but not pregnancy, reduced ID risk: RRs (95% CIs) were 0.89 (0.79, 0.998) for placebo/iron compared to placebo/placebo, 0.79 (0.63, 0.98) for placebo/iron compared to iron/placebo, 0.87 (0.77, 0.98) for iron/iron compared to placebo/placebo, and 0.86 (0.77, 0.97) for iron/iron compared to iron/placebo. However, >60% of infants still had ID at 9 mo. Receiving more bottles of iron in infancy was associated with better infant iron status at 9 mo but only among iron-supplemented infants whose mothers were also iron supplemented (i.e., the iron/iron group). There were no group differences in hospitalizations or illnesses and no adverse effects on growth overall or among infants who were iron sufficient at birth., Conclusions: Iron supplementation in Chinese infants reduced ID at 9 mo without adverse effects on growth or illness. Effects of iron supplementation in pregnancy were observed only when higher amounts of iron were distributed in infancy. This trial was registered at clinicaltrials.gov as NCT00613717., (© 2016 American Society for Nutrition.)
- Published
- 2016
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72. Delocalization and Valence Tautomerism in Vanadium Tris(iminosemiquinone) Complexes.
- Author
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Bendix J and Clark KM
- Abstract
To survey the noninnocence of bis(arylimino) acenaphthene (BIAN) ligands (L) in complexes with early metals, the homoleptic vanadium complex, [V(L)3 ] (1), and its monocation, [V(L)3 ]PF6 (2), were synthesized. These complexes were found to have a very rich electronic behavior, whereby 1 displays strong electronic delocalization and 2 can be observed in unprecedented valence tautomeric forms. The oxidation states of the metal and ligand components in these complexes were assigned by using spectroscopic, crystallographic, and magnetic analyses. Complex 1 was identified as [V(IV) (L(red) )(L(.) )2 ] (L(red) =N,N'-bis(3,5-dimethylphenylamido)acenaphthylene; L(.) =N,N'-bis(3,5-dimethylphenylimino)acenaphthenesemiquinonate). Complex 2 was determined to be [V(V) (L(red) )(L(.) )2 ](+) at T<150 K and [V(IV) (L(.) )3 ](+) at T>150 K. Cyclic voltammetry experiments reveal six quasi-reversible processes, thus indicating the potential of this metal-ligand combination in catalysis or materials applications., (© 2016 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.)
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- 2016
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73. Detection of the number of changes in a display in working memory.
- Author
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Cowan N, Hardman K, Saults JS, Blume CL, Clark KM, and Sunday MA
- Subjects
- Attention, Awareness, Female, Humans, Judgment, Male, Metacognition, Models, Psychological, Photic Stimulation, Visual Perception, Memory, Short-Term, Psychological Tests
- Abstract
Here we examine a new task to assess working memory for visual arrays in which the participant must judge how many items changed from a studied array to a test array. As a clue to processing, on some trials in the first 2 experiments, participants carried out a metamemory judgment in which they were to decide how many items were in working memory. Trial-to-trial fluctuations in these working memory storage judgments correlated with performance fluctuations within an individual, indicating a need to include trial-to-trial variation within capacity models (through either capacity fluctuation or some other attention parameter). Mathematical modeling of the results achieved a good fit to a complex pattern of results, suggesting that working memory capacity limits can apply even to judgments that involve an entire array rather than just a single item that may have changed, thus providing the expected conscious access to at least some of the contents of working memory., ((c) 2016 APA, all rights reserved).)
- Published
- 2016
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74. Mild cognitive impairment (MCI) in long-term care patients: subtype classification and occurrence.
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Mansbach WE, Mace RA, and Clark KM
- Subjects
- Aged, Aged, 80 and over, Female, Humans, Long-Term Care, Male, Middle Aged, Assisted Living Facilities statistics & numerical data, Cognitive Dysfunction classification, Homes for the Aged statistics & numerical data, Nursing Homes statistics & numerical data
- Abstract
Objectives: This study examines mild cognitive impairment (MCI) in long-term care settings by identifying and quantifying MCI subtypes in a combined sample of nursing home and assisted-living patients. We compared impairment thresholds of 1-SD and 1.5-SD to determine if different cut-offs differentially affect occurrence rates., Method: One hundred and eight participants who met general criteria for MCI were included for the purposes of this study. The general diagnosis of MCI was based on criteria. Participants were further grouped into MCI subtypes. Based on previously established norms, Brief Cognitive Assessment Tool (BCAT) factor scores were used to assess whether MCI participants met either the 1-SD and 1.5-SD impairment thresholds for memory, executive functions, and attentional capacity., Results: Using both 1-SD and 1.5-SD impairment thresholds, three clear MCI subtypes were identified: amnestic, single-domain; non-amnestic, single-domain (executive); and amnestic, multi-domain (memory and executive). A fourth category (undifferentiated) was identified in patients who did not meet criteria for a distinct MCI subtype, but still had cognitive impairments. The stricter impairment threshold of 1.5-SD resulted in fewer patients classified as having any of the three domain-specific subtypes., Conclusion: Based on a sample of nursing home and assisted-living patients, we identified three MCI subtypes, and a fourth category consisting of participants with general MCI, but without clear evidence of domain-specific cognitive impairment. When selecting impairment thresholds, one should consider the impact on the identification of MCI subtypes and the probability of misdiagnoses.
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- 2016
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75. Rapid Cognitive Assessment of Nursing Home Residents: A Comparison of the Brief Interview for Mental Status (BIMS) and Brief Cognitive Assessment Tool-Short Form (BCAT-SF).
- Author
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Mace RA, Mansbach WE, and Clark KM
- Subjects
- Aged, Female, Geriatric Assessment methods, Humans, Neuropsychological Tests, Nursing Homes, Psychometrics instrumentation, Cognition Disorders diagnosis, Interview, Psychological standards, Nursing Diagnosis standards
- Abstract
In nursing homes, the ability to identify residents with cognitive impairment is critical; however, many providers fail to address symptoms of dementia due to insufficient time to assess cognition. In the current study, the authors compared two rapidly administered instruments, the Brief Interview for Mental Status (BIMS) and Brief Cognitive Assessment Tool-Short Form (BCAT-SF), in predicting specific cognitive stages. Two hundred twenty-five nursing home residents who were referred for neurocognitive evaluation and met inclusion criteria participated in the study. Both cognitive instruments were found to predict cognitive diagnoses generally, but only the BCAT-SF demonstrated sensitivity in differentiating among all cognitive levels. Receiver operating characteristic analyses did not confirm cutoff scores reported in the original BIMS study. However, sensitivity (0.91) and specificity (0.96) values for the BCAT-SF were robust for differentiating between dementia and non-dementia. The BCAT-SF appears to be a more sensitive instrument for predicting cognitive stages than the BIMS for nursing home residents., (Copyright 2016, SLACK Incorporated.)
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- 2016
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76. Hypertriglyceridemic subjects exhibit an accumulation of small dense chylomicron particles in the fasting state.
- Author
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Irawati D, Mamo JC, Soares MJ, Slivkoff-Clark KM, and James AP
- Subjects
- Aged, Anthropometry, Apolipoprotein B-100 blood, Apolipoprotein B-48 blood, Blood Glucose analysis, Cross-Sectional Studies, Fasting, Female, Humans, Insulin blood, Lipids blood, Lipoproteins, HDL blood, Lipoproteins, VLDL blood, Male, Middle Aged, Particle Size, Risk Factors, Triglycerides blood, Chylomicrons blood, Hypertriglyceridemia blood
- Abstract
Aim: Normocholesterolemic subjects with elevated fasting plasma triglycerides are at increased risk of atherosclerosis through mechanisms that are not yet delineated. We hypothesized that elevated plasma triglyceride is associated with increased vascular exposure to pro-atherogenic lipoprotein remnants. To test this hypothesis, the abundance, and size distribution of chylomicron particles were determined in individuals with and without hypertriglyceridemia., Methods: Twelve hypertriglyceridemic subjects (HTG group, triglyceride concentration ≥1.7 mmol/L) and twelve normotriglyceridemic subjects (NTG group) matched for age and gender were studied. The distribution of chylomicron particles was assessed by determining the fasting concentration of apo B-48 in serum lipoprotein fractions with Svedberg flotation rates of (Sf) > 400, Sf 20-400 and Sf < 20., Results: The total concentration of apo B-48 in subjects with HTG was almost twice that observed in NTG controls with ∼80% of the increase residing in the Sf < 20 fraction (HTG: 8.7 ± 1.0 μg/mL vs NTG: 5.0 ± 0.6 μg/mL; P = 0.016). Significantly greater concentrations of apo B-48 were also observed in the less dense Sf 20-400 (HTG: 1.1 ± 0.2 μg/mL vs NTG: 0.4 ± 0.07 μg/mL; P < 0.001) and the Sf > 400 (HTG: 1.1 ± 0.3 μg/mL vs NTG: 0.3 ± 0.04 μg/mL; P < 0.001) fractions. An accumulation of triglyceride was also observed across all lipoprotein fractions in HTG subjects compared to NTG (Sf 400 & Sf 20-400: P < 0.001 and Sf < 20: P = 0.013)., Conclusion: Normocholesterolemic, moderately hypertriglyceridemic subjects are at increased atherogenic risk due to greater apo B-48 concentration in the small, dense lipoprotein fraction., (Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.)
- Published
- 2015
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77. Prenatal Iron Supplementation Reduces Maternal Anemia, Iron Deficiency, and Iron Deficiency Anemia in a Randomized Clinical Trial in Rural China, but Iron Deficiency Remains Widespread in Mothers and Neonates.
- Author
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Zhao G, Xu G, Zhou M, Jiang Y, Richards B, Clark KM, Kaciroti N, Georgieff MK, Zhang Z, Tardif T, Li M, and Lozoff B
- Subjects
- Adult, Anemia, Iron-Deficiency epidemiology, China epidemiology, Female, Humans, Infant, Newborn, Iron Deficiencies, Maternal Nutritional Physiological Phenomena, Pregnancy, Young Adult, Anemia, Iron-Deficiency prevention & control, Dietary Supplements, Iron administration & dosage, Rural Population
- Abstract
Background: Previous trials of prenatal iron supplementation had limited measures of maternal or neonatal iron status., Objective: The purpose was to assess effects of prenatal iron-folate supplementation on maternal and neonatal iron status., Methods: Enrollment occurred June 2009 through December 2011 in Hebei, China. Women with uncomplicated singleton pregnancies at ≤20 wk gestation, aged ≥18 y, and with hemoglobin ≥100 g/L were randomly assigned 1:1 to receive daily iron (300 mg ferrous sulfate) or placebo + 0.40 mg folate from enrollment to birth. Iron status was assessed in maternal venous blood (at enrollment and at or near term) and cord blood. Primary outcomes were as follows: 1) maternal iron deficiency (ID) defined in 2 ways as serum ferritin (SF) <15 μg/L and body iron (BI) <0 mg/kg; 2) maternal ID anemia [ID + anemia (IDA); hemoglobin <110 g/L]; and 3) neonatal ID (cord blood ferritin <75 μg/L or zinc protoporphyrin/heme >118 μmol/mol)., Results: A total of 2371 women were randomly assigned, with outcomes for 1632 women or neonates (809 placebo/folate, 823 iron/folate; 1579 mother-newborn pairs, 37 mothers, 16 neonates). Most infants (97%) were born at term. At or near term, maternal hemoglobin was significantly higher (+5.56 g/L) for iron vs. placebo groups. Anemia risk was reduced (RR: 0.53; 95% CI: 0.43, 0.66), as were risks of ID (RR: 0.74; 95% CI: 0.69, 0.79 by SF; RR: 0.65; 95% CI: 0.59, 0.71 by BI) and IDA (RR: 0.49; 95% CI: 0.38, 0.62 by SF; RR: 0.51; 95% CI: 0.40, 0.65 by BI). Most women still had ID (66.8% by SF, 54.7% by BI). Adverse effects, all minor, were similar by group. There were no differences in cord blood iron measures; >45% of neonates in each group had ID. However, dose-response analyses showed higher cord SF with more maternal iron capsules reported being consumed (β per 10 capsules = 2.60, P < 0.05)., Conclusions: Prenatal iron supplementation reduced anemia, ID, and IDA in pregnant women in rural China, but most women and >45% of neonates had ID, regardless of supplementation. This trial was registered at clinicaltrials.gov as NCT02221752., (© 2015 American Society for Nutrition.)
- Published
- 2015
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78. Exploring age differences in visual working memory capacity: is there a contribution of memory for configuration?
- Author
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Cowan N, Saults JS, and Clark KM
- Subjects
- Adult, Child, Color Perception physiology, Female, Form Perception physiology, Humans, Male, Child Development physiology, Memory, Short-Term physiology, Pattern Recognition, Visual physiology
- Abstract
Recent research has shown marked developmental increases in the apparent capacity of working memory. This recent research is based largely on performance on tasks in which a visual array is to be retained briefly for comparison with a subsequent probe display. Here we examined a possible theoretical alternative (or supplement) to a developmental increase in working memory in which children could improve in the ability to combine items in an array to form a coherent configuration. Elementary school children and adults received, on each trial, an array of colored spots to be remembered. On some trials, we provided structure in the probe display to facilitate the formation of a mental representation in which a coherent configuration is encoded. This stimulus structure in the probe display helped younger children, and thus reduced the developmental trend, but only on trials in which the participants were held responsible for the locations of items in the array. We conclude that, in addition to the development of the ability to form precise spatial configurations from items, the evidence is consistent with the existence of an actual developmental increase in working memory capacity for objects in an array., (Copyright © 2015 Elsevier Inc. All rights reserved.)
- Published
- 2015
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79. The Brief Anxiety and Depression Scale (BADS): a new instrument for detecting anxiety and depression in long-term care residents.
- Author
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Mansbach WE, Mace RA, and Clark KM
- Subjects
- Aged, Aged, 80 and over, Anxiety psychology, Anxiety Disorders diagnosis, Anxiety Disorders psychology, Depression psychology, Depressive Disorder, Major diagnosis, Depressive Disorder, Major psychology, Female, Humans, Long-Term Care statistics & numerical data, Male, Middle Aged, Neuropsychological Tests, Nursing Homes statistics & numerical data, Psychometrics, Reproducibility of Results, Anxiety diagnosis, Depression diagnosis, Long-Term Care psychology, Psychiatric Status Rating Scales
- Abstract
Background: Depression and anxiety are common among long-term care residents, yet both appear to be under-recognized and under-treated. In our survey of 164 geriatric health care professionals from 34 U.S. states, 96% of respondents reported that a new instrument that rapidly assesses both depression and anxiety is needed. The Brief Anxiety and Depression Scale (BADS) is a new screening tool that can identify possible major depressive episodes (MDE) and generalized anxiety disorders (GAD) in long-term care residents., Methods: The psychometric properties of the BADS were investigated in a sample of 224 U.S. long-term care residents (aged 80.52 ± 9.07). Participants completed a battery of several individually administered mood and cognitive tests, including the BADS. MDE and GAD were diagnosed based on the DSM-IV-TR criteria., Results: Adequate internal consistency and construct validity were found. A principle component analysis (PCA) revealed an Anxiety Factor and a Depression Factor, which explained 50.26% of the total variance. The Anxiety Factor had a sensitivity of 0.73 and specificity of 0.81 for identifying GAD (PPV = 0.69, NPV = 0.84). The Depression Factor had a sensitivity of 0.76 and a specificity of 0.73 for identifying MDE (PPV = 0.77, NPV = 0.72)., Conclusions: The BADS appears to be a reliable and valid screening instrument for MDE and GAD in long-term residents. The BADS can be rapidly administered, is sensitive to mood diagnoses in both patients without dementia and with dementia, and produces separate depression and anxiety factor scores that can be used clinically to identify probable mood diagnoses.
- Published
- 2015
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80. A practical guide to the application of the IUCN Red List of Ecosystems criteria.
- Author
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Rodríguez JP, Keith DA, Rodríguez-Clark KM, Murray NJ, Nicholson E, Regan TJ, Miller RM, Barrow EG, Bland LM, Boe K, Brooks TM, Oliveira-Miranda MA, Spalding M, and Wit P
- Subjects
- Classification methods, Conservation of Natural Resources methods, Ecosystem, Endangered Species statistics & numerical data, Models, Biological, Risk Assessment methods
- Abstract
The newly developed IUCN Red List of Ecosystems is part of a growing toolbox for assessing risks to biodiversity, which addresses ecosystems and their functioning. The Red List of Ecosystems standard allows systematic assessment of all freshwater, marine, terrestrial and subterranean ecosystem types in terms of their global risk of collapse. In addition, the Red List of Ecosystems categories and criteria provide a technical base for assessments of ecosystem status at the regional, national, or subnational level. While the Red List of Ecosystems criteria were designed to be widely applicable by scientists and practitioners, guidelines are needed to ensure they are implemented in a standardized manner to reduce epistemic uncertainties and allow robust comparisons among ecosystems and over time. We review the intended application of the Red List of Ecosystems assessment process, summarize 'best-practice' methods for ecosystem assessments and outline approaches to ensure operational rigour of assessments. The Red List of Ecosystems will inform priority setting for ecosystem types worldwide, and strengthen capacity to report on progress towards the Aichi Targets of the Convention on Biological Diversity. When integrated with other IUCN knowledge products, such as the World Database of Protected Areas/Protected Planet, Key Biodiversity Areas and the IUCN Red List of Threatened Species, the Red List of Ecosystems will contribute to providing the most complete global measure of the status of biodiversity yet achieved., (© 2015 The Author(s) Published by the Royal Society. All rights reserved.)
- Published
- 2015
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81. Preliminary investigation of the psychometric properties of the Korean version of the brief cognitive assessment tool-short form for Korean American nursing home residents.
- Author
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Mansbach WE, Mace RA, and Clark KM
- Subjects
- Asian, Female, Humans, Male, Neuropsychological Tests, Republic of Korea, Cognition, Inpatients, Nursing Homes, Psychometrics
- Abstract
The authors of the current article developed and investigated the psychometric properties of a Korean version of the Brief Cognitive Assessment Tool-Short Form (BCAT-SF-K) to better understand cognitive functioning of Korean American nursing home residents. In Step I, normative values were established for the BCAT-SF-K based on a sample of Korean American community-dwelling older adults (n = 34). In Step II, the authors confirmed construct validity for the BCAT-SF-K in a sample of Korean American nursing home residents (n = 26), described cognitive levels, and reported key demographics. In the nursing home sample, 84.6% of individuals had severe cognitive impairment, 7.7% had mild impairment, and 7.7% had normal cognition. The BCAT-SF-K appears to be a reliable cognitive screening measure for Korean American nursing home residents. Based on the current study's findings, Korean American nursing home residents are both older and more cognitively impaired than their American-born nursing home counterparts. Study findings are discussed in relation to improving care for these vulnerable nursing home residents., (Copyright 2015, SLACK Incorporated.)
- Published
- 2015
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82. Finding the "Conservation" in Conservation Genetics--Progress in Latin America.
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Rodríguez-Clark KM, Oliveira-Miranda MA, Aguilera Meneses M, Martino Á, Méndez MA, Miyaki C, Montiel-Villalobos MG, de Oliveira-Miranda RM, Poulin E, Ruzzante D, and Solé-Cava A
- Subjects
- Latin America, Conservation of Natural Resources, Ecology education, Genetic Variation
- Published
- 2015
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- View/download PDF
83. Knowledge cannot explain the developmental growth of working memory capacity.
- Author
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Cowan N, Ricker TJ, Clark KM, Hinrichs GA, and Glass BA
- Subjects
- Adolescent, Adult, Age Factors, Child, Female, Humans, Male, Photic Stimulation, Retention, Psychology, Verbal Learning physiology, Young Adult, Child Development physiology, Knowledge, Memory, Short-Term physiology
- Abstract
According to some views of cognitive growth, the development of working memory capacity can account for increases in the complexity of cognition. It has been difficult to ascertain, though, that there actually is developmental growth in capacity that cannot be attributed to other developing factors. Here we assess the role of item familiarity. We document developmental increases in working memory for visual arrays of English letters versus unfamiliar characters. Although letter knowledge played a special role in development between the ages of 6 and 8 years, children with adequate letter knowledge showed practically the same developmental growth in normalized functions for letters and unfamiliar characters. The results contribute to a growing body of evidence that the developmental improvement in working memory does not wholly stem from supporting processes such as encoding, mnemonic strategies, and knowledge. A video abstract is available at: https://www.youtube.com/watch?v=LJdqErLR2Hs&feature=youtu.be., (© 2014 John Wiley & Sons Ltd.)
- Published
- 2015
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84. Differentiating levels of cognitive functioning: a comparison of the Brief Interview for Mental Status (BIMS) and the Brief Cognitive Assessment Tool (BCAT) in a nursing home sample.
- Author
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Mansbach WE, Mace RA, and Clark KM
- Subjects
- Aged, Aged, 80 and over, Female, Humans, Male, Middle Aged, Cognition Disorders diagnosis, Neuropsychological Tests standards, Nursing Homes, Psychiatric Status Rating Scales standards, Psychometrics instrumentation
- Abstract
Objectives: In US nursing homes, cognitive assessment has been an essential component of the federally mandated Minimum Data Set assessment system, inclusive of the Brief Interview for Mental Status (BIMS) for identifying possible cognitive impairment. We compare it with the Brief Cognitive Assessment Tool (BCAT) to determine which instrument is more sensitive in differentiating degrees of cognitive functioning in nursing home residents. We attempt to cross-validate the psychometric properties of both measures., Method: Two hundred twenty-nine individuals residing in a Maryland skilled nursing facility were referred for neurocognitive evaluation over a 10-month period. One hundred eighty-nine of these residents met inclusion criteria by completing the BCAT and BIMS, and were aged 60 or older., Results: The BIMS and the BCAT were confirmed to have strong internal consistency reliability and construct validity. Both cognitive tools were found to predict cognitive diagnoses generally, but only the BCAT was able to identify residents at all specific cognitive levels. The BIMS did not differentiate between residents with normal cognition and those with mild cognitive impairment, or between mild and moderate dementia. Both measures demonstrated high specificity and positive predictive values for identifying severe cognitive impairment or probable dementia. The BIMS had lower sensitivity and negative predictive values for identifying dementia compared to the BCAT. The BCAT accounted for an additional 47% of the variance in dementia diagnoses over and above BIMS scores., Conclusion: Based on these findings, the BCAT appears to be more sensitive than the BIMS in predicting cognitive level for nursing home residents.
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- 2014
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85. Iron supplementation in infancy contributes to more adaptive behavior at 10 years of age.
- Author
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Lozoff B, Castillo M, Clark KM, Smith JB, and Sturza J
- Subjects
- Anemia, Iron-Deficiency prevention & control, Child, Chile, Depression prevention & control, Depression psychology, Double-Blind Method, Emotions physiology, Female, Follow-Up Studies, Humans, Infant, Male, Socioeconomic Factors, Adaptation, Psychological drug effects, Dietary Supplements, Emotions drug effects, Infant Nutritional Physiological Phenomena, Iron, Dietary administration & dosage
- Abstract
Most studies of behavioral/developmental effects of iron deficiency anemia (IDA) or iron supplementation in infancy have found social-emotional differences. Differences could relate to behavioral inhibition or lack of positive affect and altered response to reward. To determine long-term behavioral effects, the study was a follow-up of a randomized controlled trial of behavioral/developmental effects of preventing IDA in infancy. Healthy Chilean infants free of IDA at age 6 mo were randomly assigned to iron supplementation or no added iron (formula with iron/powdered cow milk, vitamins with/without iron) from ages 6 to 12 mo. At age 10 y, 59% (666 of 1123) and 68% (366 of 534) of iron-supplemented and no-added-iron groups were assessed. Social-emotional outcomes included maternal-reported behavior problems, self-reported behavior, examiner ratings, and video coding of a social stress task and gamelike paradigms. Examiners rated the iron-supplemented group as more cooperative, confident, persistent after failure, coordinated, and direct and reality-oriented in speech and working harder after praise compared with the no-added-iron group. In a task designed to elicit positive affect, supplemented children spent more time laughing and smiling together with their mothers and started smiling more quickly. In the social stress task they smiled and laughed more and needed less prompting to complete the task. All P values were <0.05; effect sizes were 0.14-0.36. There were no differences in behaviors related to behavioral inhibition, such as anxiety/depression or social problems. In sum, iron supplementation in infancy was associated with more adaptive behavior at age 10 y, especially in affect and response to reward, which may improve performance at school and work, mental health, and personal relationships., (© 2014 American Society for Nutrition.)
- Published
- 2014
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86. HPV E6/E7 RNA in situ hybridization signal patterns as biomarkers of three-tier cervical intraepithelial neoplasia grade.
- Author
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Evans MF, Peng Z, Clark KM, Adamson CS, Ma XJ, Wu X, Wang H, Luo Y, and Cooper K
- Subjects
- Adolescent, Adult, Cohort Studies, Cyclin-Dependent Kinase Inhibitor p16 metabolism, Disease Progression, Female, Genes, Viral, Genotype, Humans, In Situ Hybridization, Middle Aged, Papillomaviridae classification, Papillomaviridae genetics, Papillomavirus Infections diagnosis, Papillomavirus Infections virology, Young Adult, Biomarkers metabolism, DNA-Binding Proteins metabolism, Oncogene Proteins, Viral metabolism, RNA, Viral metabolism, Uterine Cervical Dysplasia diagnosis, Uterine Cervical Dysplasia virology
- Abstract
Cervical lesion grading is critical for effective patient management. A three-tier classification (cervical intraepithelial neoplasia [CIN] grade 1, 2 or 3) based on H&E slide review is widely used. However, for reasons of considerable inter-observer variation in CIN grade assignment and for want of a biomarker validating a three-fold stratification, CAP-ASCCP LAST consensus guidelines recommend a two-tier system: low- or high-grade squamous intraepithelial lesions (LSIL or HSIL). In this study, high-risk HPV E6/E7 and p16 mRNA expression patterns in eighty-six CIN lesions were investigated by RNAscope chromogenic in situ hybridization (CISH). Specimens were also screened by immunohistochemistry for p16INK4a (clone E6H4), and by tyramide-based CISH for HPV DNA. HPV genotyping was performed by GP5+/6+ PCR combined with cycle-sequencing. Abundant high-risk HPV RNA CISH signals were detected in 26/32 (81.3%) CIN 1, 22/22 (100%) CIN 2 and in 32/32 (100%) CIN 3 lesions. CIN 1 staining patterns were typified (67.7% specimens) by abundant diffusely staining nuclei in the upper epithelial layers; CIN 2 lesions mostly (66.7%) showed a combination of superficial diffuse-stained nuclei and multiple dot-like nuclear and cytoplasmic signals throughout the epithelium; CIN 3 lesions were characterized (87.5%) by multiple dot-like nuclear and cytoplasmic signals throughout the epithelial thickness and absence/scarcity of diffusely staining nuclei (trend across CIN grades: P<0.0001). These data are consistent with productive phase HPV infections exemplifying CIN 1, transformative phase infections CIN 3, whereas CIN 2 shows both productive and transformative phase elements. Three-tier data correlation was not found for the other assays examined. The dual discernment of diffuse and/or dot-like signals together with the assay's high sensitivity for HPV support the use of HPV E6/E7 RNA CISH as an adjunct test for deciding lesion grade when CIN 2 grading may be beneficial (e.g. among young women) or when 'LSIL vs. HSIL' assignment is equivocal.
- Published
- 2014
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87. Science, not blame: pediatric obesity update.
- Author
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Clark KM
- Subjects
- Child, Digestion physiology, Epigenomics, Health Behavior, Humans, Intestines microbiology, Obesity microbiology, Obesity prevention & control, Obesity physiopathology
- Published
- 2014
- Full Text
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88. Modulating the Copper-Sulfur Interaction in Type 1 Blue Copper Azurin by Replacing Cys112 with Nonproteinogenic Homocysteine.
- Author
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Clark KM, Yu Y, van der Donk WA, Blackburn N, and Lu Y
- Abstract
The Cu-S
Cys interaction is known to play a dominant role in defining the type 1 (T1) blue copper center with respect to both its electronic structure and electron transfer function. Despite this importance, its role has yet to be probed by mutagenesis studies without dramatic change of its T1 copper character. We herein report replacement of the conserved Cys112 in azurin with the nonproteinogenic amino acid homocysteine. Based on electronic absorption, electron paramagnetic resonance, and extended x-ray absorption fine structural spectroscopic studies, this variant displays typical type 1 copper site features. Surprisingly, instead of increasing the strength of the Cu-sulfur interaction by the introduction of the extra methylene group, the Cys112Hcy azurin showed a decrease in the covalent interaction between SHcy and Cu(II) when compared with the WT SCys -Cu(II) interaction. This is likely due to geometric adjustment of the center that resulted in the copper ion moving out of the trigonal plane defined by two histidines and one Hcy and closer to Met121. These structural changes resulted in an increase of reduction potential by 35 mV, consistent with lower Cu-S covalency. These results suggest that the Cu-SCys interaction is close to being optimal in native blue copper protein. It also demonstrates the power of using nonproteinogenic amino acids in addressing important issues in bioinorganic chemistry.- Published
- 2014
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89. Preliminary investigation of the Kitchen Picture Test (KPT): a new screening test of practical judgment for older adults.
- Author
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Mansbach WE, MacDougall EE, Clark KM, and Mace RA
- Subjects
- Age Factors, Aged, Aged, 80 and over, Female, Humans, Male, Middle Aged, Psychometrics, Reproducibility of Results, Dementia diagnosis, Executive Function, Judgment, Neuropsychological Tests
- Abstract
Judgment is widely recognized as an important executive function, and deficits in judgment can lead to health risks, safety concerns, and hospitalizations. Surprisingly, relatively few tests of judgment have been developed specifically for older adults--a population particularly vulnerable to executive and functional declines. The Kitchen Picture Test (KPT) is a new screening measure of practical judgment. In two independent studies (Study 1, N = 99 nursing home patients; Study 2, N = 163 nursing home and assisted living patients), psychometric analyses confirmed strong evidence for reliability, construct validity, and predictive validity. A receiver operating characteristic (ROC) curve was calculated from sensitivity and 1-specificity values for diagnoses of dementia versus no dementia. A KPT cut score can be used for identifying persons to be referred to appropriate health-care professionals who have specific expertise in the evaluation and treatment of cognitive impairment.
- Published
- 2014
- Full Text
- View/download PDF
90. Story recall and word lists: differential and combined utilities in predicting cognitive diagnosis.
- Author
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Mansbach WE, Mace RA, and Clark KM
- Subjects
- Aged, Aged, 80 and over, Female, Geriatric Assessment, Humans, Male, Middle Aged, Psychiatric Status Rating Scales, Regression Analysis, Cognition physiology, Cognition Disorders diagnosis, Mental Recall physiology, Neuropsychological Tests, Verbal Learning physiology
- Abstract
Objectives: Verbal memory assessment metrics are an essential component of cognitive screening tools. We compared the relative utilities of word list and story recall metrics in predicting cognitive functioning in nondemented and demented nursing home patients. We selected memory metrics from the Brief Cognitive Assessment Tool (BCAT) and the Brief Interview for Mental Status (BIMS). The BCAT incorporates both word lists and story recall metrics, while the BIMS only has a word list feature., Method: Two hundred and thirty-nine individuals residing in a Maryland skilled nursing facility were referred for neurocognitive evaluation over a one-year period. These residents met inclusion criteria for retrospective data analysis by completing the BCAT and BIMS and were aged 60 or older., Results: For the entire sample and for demented individuals, all four verbal memory metrics significantly predicted cognitive diagnosis. For nondemented individuals, only the BCAT delayed word list significantly predicted cognitive diagnosis. There appears to be enhanced utility in using both verbal memory metric types, as the inclusion of word list and story recall was a stronger predictor of cognitive diagnosis than any individual verbal memory metric., Conclusion: This study highlights the importance of using cognitive screening tools that contain both story recall and word list metrics. This is particularly true in long-term care settings where the base rate of cognitive impairment is high.
- Published
- 2014
- Full Text
- View/download PDF
91. Functional significance of early-life iron deficiency: outcomes at 25 years.
- Author
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Lozoff B, Smith JB, Kaciroti N, Clark KM, Guevara S, and Jimenez E
- Subjects
- Adaptation, Psychological, Adult, Costa Rica, Emotions, Female, Follow-Up Studies, Humans, Infant, Iron Deficiencies, Male, Marital Status, Mass Screening, Mental Health, Social Class, Surveys and Questionnaires, Anemia, Iron-Deficiency complications, Anemia, Iron-Deficiency diagnosis, Educational Status
- Abstract
Objective: To evaluate adulthood function following chronic iron deficiency in infancy., Study Design: At 25 years, we compared 33 subjects with chronic iron deficiency in infancy to 89 who were iron-sufficient before and/or after iron therapy. Outcomes included education, employment, marital status, and physical and mental health., Results: Adjusting for sex and socioeconomic status, a higher proportion of the group with chronic iron deficiency did not complete secondary school (58.1% vs 19.8% in iron-sufficient group; Wald value = 8.74; P = .003), were not pursuing further education/training (76.1% vs 31.5%; Wald value = 3.01; P = .08; suggestive trend), and were single (83.9% vs 23.7%, Wald value = 4.49; P = .03). They reported poorer emotional health and more negative emotions and feelings of dissociation/detachment. Results were similar in secondary analyses comparing the chronic iron-deficient group with subjects in the iron-sufficient group who had been iron-deficient before treatment in infancy. Path analysis showed direct paths for chronic iron deficiency in infancy and being single and more detachment/dissociation at 25 years. There were indirect paths for chronic iron deficiency and not completing secondary school via poorer cognitive functioning in early adolescence and more negative emotions via behavior problems in adolescence, indicating a cascade of adverse outcomes., Conclusion: The observational nature of this study limits our ability to draw causal inference, even when controlling for background factors. Nonetheless, our results indicate substantial loss of human potential. There may be broader societal implications, considering that many adults worldwide had chronic iron deficiency in infancy. Iron deficiency can be prevented or treated before it becomes chronic or severe., (Copyright © 2013 Mosby, Inc. All rights reserved.)
- Published
- 2013
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92. Scientific foundations for an IUCN Red List of ecosystems.
- Author
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Keith DA, Rodríguez JP, Rodríguez-Clark KM, Nicholson E, Aapala K, Alonso A, Asmussen M, Bachman S, Basset A, Barrow EG, Benson JS, Bishop MJ, Bonifacio R, Brooks TM, Burgman MA, Comer P, Comín FA, Essl F, Faber-Langendoen D, Fairweather PG, Holdaway RJ, Jennings M, Kingsford RT, Lester RE, Mac Nally R, McCarthy MA, Moat J, Oliveira-Miranda MA, Pisanu P, Poulin B, Regan TJ, Riecken U, Spalding MD, and Zambrano-Martínez S
- Subjects
- Biodiversity, Conservation of Natural Resources methods, Ecosystem, Endangered Species, Models, Theoretical, Risk Assessment methods
- Abstract
An understanding of risks to biodiversity is needed for planning action to slow current rates of decline and secure ecosystem services for future human use. Although the IUCN Red List criteria provide an effective assessment protocol for species, a standard global assessment of risks to higher levels of biodiversity is currently limited. In 2008, IUCN initiated development of risk assessment criteria to support a global Red List of ecosystems. We present a new conceptual model for ecosystem risk assessment founded on a synthesis of relevant ecological theories. To support the model, we review key elements of ecosystem definition and introduce the concept of ecosystem collapse, an analogue of species extinction. The model identifies four distributional and functional symptoms of ecosystem risk as a basis for assessment criteria: A) rates of decline in ecosystem distribution; B) restricted distributions with continuing declines or threats; C) rates of environmental (abiotic) degradation; and D) rates of disruption to biotic processes. A fifth criterion, E) quantitative estimates of the risk of ecosystem collapse, enables integrated assessment of multiple processes and provides a conceptual anchor for the other criteria. We present the theoretical rationale for the construction and interpretation of each criterion. The assessment protocol and threat categories mirror those of the IUCN Red List of species. A trial of the protocol on terrestrial, subterranean, freshwater and marine ecosystems from around the world shows that its concepts are workable and its outcomes are robust, that required data are available, and that results are consistent with assessments carried out by local experts and authorities. The new protocol provides a consistent, practical and theoretically grounded framework for establishing a systematic Red List of the world's ecosystems. This will complement the Red List of species and strengthen global capacity to report on and monitor the status of biodiversity.
- Published
- 2013
- Full Text
- View/download PDF
93. Structure of the integral membrane protein CAAX protease Ste24p.
- Author
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Pryor EE Jr, Horanyi PS, Clark KM, Fedoriw N, Connelly SM, Koszelak-Rosenblum M, Zhu G, Malkowski MG, Wiener MC, and Dumont ME
- Subjects
- Amino Acid Sequence, Catalytic Domain, Crystallography, X-Ray, Molecular Sequence Data, Protein Structure, Secondary, Substrate Specificity, Cell Membrane enzymology, Membrane Proteins chemistry, Metalloendopeptidases chemistry, Saccharomyces cerevisiae Proteins chemistry
- Abstract
Posttranslational lipidation provides critical modulation of the functions of some proteins. Isoprenoids (i.e., farnesyl or geranylgeranyl groups) are attached to cysteine residues in proteins containing C-terminal CAAX sequence motifs (where A is an aliphatic residue and X is any residue). Isoprenylation is followed by cleavage of the AAX amino acid residues and, in some cases, by additional proteolytic cuts. We determined the crystal structure of the CAAX protease Ste24p, a zinc metalloprotease catalyzing two proteolytic steps in the maturation of yeast mating pheromone a-factor. The Ste24p core structure is a ring of seven transmembrane helices enclosing a voluminous cavity containing the active site and substrate-binding groove. The cavity is accessible to the external milieu by means of gaps between splayed transmembrane helices. We hypothesize that cleavage proceeds by means of a processive mechanism of substrate insertion, translocation, and ejection.
- Published
- 2013
- Full Text
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94. Facial erythematous annular plaques: a case of annular Demodex facial dermatitis?
- Author
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Martinez-Diaz GJ, Clark KM, Vasquez JG, and English JC 3rd
- Subjects
- Female, Humans, Young Adult, Facial Dermatoses diagnosis, Facial Dermatoses parasitology, Mite Infestations diagnosis
- Published
- 2012
- Full Text
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95. Important role of CCR2 in a murine model of coronary vasculitis.
- Author
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Martinez HG, Quinones MP, Jimenez F, Estrada C, Clark KM, Suzuki K, Miura N, Ohno N, Ahuja SK, and Ahuja SS
- Subjects
- Animals, Aorta pathology, B-Lymphocytes immunology, Bone Marrow Cells pathology, Candida albicans cytology, Candida albicans physiology, Cell Movement, Cell Proliferation, Cell Wall metabolism, Coronary Vessels immunology, Disease Models, Animal, Immunity immunology, Inflammation complications, Inflammation pathology, Interleukin-6 metabolism, Lymphocyte Depletion, Macrophages pathology, Mice, Mice, Inbred C57BL, Monocytes pathology, Peroxidase blood, Receptors, CCR2 deficiency, Receptors, CCR5 deficiency, Receptors, CCR5 metabolism, T-Lymphocytes immunology, T-Lymphocytes, Regulatory immunology, Th17 Cells cytology, Th17 Cells immunology, Vasculitis blood, Vasculitis microbiology, Vasculitis prevention & control, Coronary Vessels pathology, Receptors, CCR2 metabolism, Vasculitis immunology
- Abstract
Background: Chemokines and their receptors play a role in the innate immune response as well as in the disruption of the balance between pro-inflammatory Th17 cells and regulatory T cells (Treg), underlying the pathogenesis of coronary vasculitis in Kawasaki disease (KD)., Results: Here we show that genetic inactivation of chemokine receptor (CCR)-2 is protective against the induction of aortic and coronary vasculitis following injection of Candida albicans water-soluble cell wall extracts (CAWS). Mechanistically, both T and B cells were required for the induction of vasculitis, a role that was directly modulated by CCR2. CAWS administration promoted mobilization of CCR2-dependent inflammatory monocytes (iMo) from the bone marrow (BM) to the periphery as well as production of IL-6. IL-6 was likely to contribute to the depletion of Treg and expansion of Th17 cells in CAWS-injected Ccr2(+/+) mice, processes that were ameliorated following the genetic inactivation of CCR2., Conclusion: Collectively, our findings provide novel insights into the role of CCR2 in the pathogenesis of vasculitis as seen in KD and highlight novel therapeutic targets, specifically for individuals resistant to first-line treatments.
- Published
- 2012
- Full Text
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96. Academy of Nutrition and Dietetics: Standards of professional performance for registered dietitians (competent, proficient, expert) in clinical nutrition management.
- Author
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Clark KM, Moore C, Trombley L, Skates J, Rogalski MJ, Schofield M, and Welch J
- Subjects
- Humans, Professional Competence standards, Societies, United States, Clinical Competence standards, Dietetics standards, Nutrition Therapy standards, Professional Practice standards
- Published
- 2012
- Full Text
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97. Synthesis and characterization of a neutral titanium tris(iminosemiquinone) complex featuring redox-active ligands.
- Author
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Clark KM, Bendix J, Heyduk AF, and Ziller JW
- Subjects
- Ligands, Models, Molecular, Molecular Structure, Oxidation-Reduction, Quantum Theory, Organometallic Compounds chemical synthesis, Organometallic Compounds chemistry, Quinones chemistry, Titanium chemistry
- Abstract
The neutral tris(semiquinonate) complex [Ti(dmp-BIAN(isq))(3)] [dmp-BIAN(isq) = N,N'-bis(3,5-dimethylphenylimino)acenaphthenesemiquinonate] was structurally, spectroscopically, and electrochemically characterized. Solid-state magnetism experiments reveal field-quenchable, enhanced temperature-independent paramagnetism (TIP). Density functional theory calculations employing the experimental geometry predicts a strong antiferromagnetic coupling, leading to an S = 0 ground state, but they also hint at spin frustration and concomitant close-lying, excited states, which cause the observed large TIP by admixture into the ground state. The dmp-BIAN(isq) ligand, which facilitates intramolecular electron transfer, was shown to undergo four quasi-reversible redox processes, demonstrating the ability of the ligand to act as an electron reservoir in complexes of early metals.
- Published
- 2012
- Full Text
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98. The effects of verbal operant training and response interruption and redirection on appropriate and inappropriate vocalizations.
- Author
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Colón CL, Ahearn WH, Clark KM, and Masalsky J
- Subjects
- Child, Child Development Disorders, Pervasive complications, Female, Humans, Male, Stereotypic Movement Disorder etiology, Time Factors, Behavior Therapy methods, Conditioning, Operant, Stereotyped Behavior physiology, Stereotypic Movement Disorder rehabilitation, Verbal Behavior physiology, Voice
- Abstract
Past research has shown that response interruption and redirection (RIRD) can effectively decrease automatically reinforced motor behavior (Hagopian & Adelinis, 2001). Ahearn, Clark, MacDonald, and Chung (2007) found that a procedural adaptation of RIRD reduced vocal stereotypy and increased appropriate vocalizations for some children, although appropriate vocalizations were not targeted directly. The purpose of the current study was to examine the effects of directly targeting appropriate language (i.e., verbal operant training) on vocal stereotypy and appropriate speech in 3 children with an autism spectrum disorder. The effects of verbal operant (i.e., tact) training were evaluated in a nonconcurrent multiple baseline design across participants. In addition, RIRD was implemented with 2 of the 3 participants to further decrease levels of vocal stereotypy. Verbal operant training alone produced slightly lower levels of stereotypy and increased appropriate vocalizations for all 3 participants; however, RIRD was required to produce acceptably low levels of stereotypy for 2 of the 3 participants.
- Published
- 2012
- Full Text
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99. The chronic effects of fish oil with exercise on postprandial lipaemia and chylomicron homeostasis in insulin resistant viscerally obese men.
- Author
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Slivkoff-Clark KM, James AP, and Mamo JC
- Abstract
Background: Visceral obesity and insulin resistance are associated with a postprandial accumulation of atherogenic chylomicron remnants that is difficult to modulate with lipid-lowering therapies. Dietary fish oil and exercise are cardioprotective interventions that can significantly modify the metabolism of TAG-rich lipoproteins. In this study, we investigated whether chronic exercise and fish oil act in combination to affect chylomicron metabolism in obese men with moderate insulin resistance., Methods: The single blind study tested the effect of fish oil, exercise and the combined treatments on fasting and postprandial chylomicron metabolism. Twenty nine men with metabolic syndrome were randomly assigned to take fish oil or placebo for four weeks, before undertaking an additional 12 week walking program. At baseline and at the end of each treatment, subjects were tested for concentrations of fasting apo B48, plasma lipids and insulin. Postprandial apo B48 and TAG kinetics were also determined following ingestion of a fat enriched meal., Results: Combining fish oil and exercise resulted in a significant reduction in the fasting apo B48 concentration, concomitant with attenuation of fasting TAG concentrations and the postprandial TAGIAUC response (p < 0.05). Fish oil by itself reduced the postprandial TAG response (p < 0.05) but not postprandial apo B48 kinetics. Individual treatments of fish oil and exercise did not correspond with improvements in fasting plasma TAG and apo B48., Conclusion: Fish oil was shown to independently improve plasma TAG homeostasis but did not resolve hyper-chylomicronaemia. Instead, combining fish oil with chronic exercise reduced the plasma concentration of pro-atherogenic chylomicron remnants; in addition it reduced the fasting and postprandial TAG response in viscerally obese insulin resistant subjects.
- Published
- 2012
- Full Text
- View/download PDF
100. Parainfluenza virus 5-based vaccine vectors expressing vaccinia virus (VACV) antigens provide long-term protection in mice from lethal intranasal VACV challenge.
- Author
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Clark KM, Johnson JB, Kock ND, Mizel SB, and Parks GD
- Subjects
- Animals, Antibodies, Neutralizing blood, Antibodies, Viral blood, Antigens, Viral immunology, CD8-Positive T-Lymphocytes immunology, Enzyme-Linked Immunosorbent Assay, Membrane Glycoproteins genetics, Mice, Mice, Inbred BALB C, Neutralization Tests, Paramyxovirinae immunology, Vaccinia virus genetics, Viral Envelope Proteins genetics, Viral Vaccines genetics, Membrane Glycoproteins immunology, Paramyxovirinae genetics, Respiratory Tract Infections immunology, Vaccinia prevention & control, Vaccinia virus immunology, Viral Envelope Proteins immunology, Viral Vaccines immunology
- Abstract
To test the potential for parainfluenza virus 5 (PIV5)-based vectors to provide protection from vaccinia virus (VACV) infection, PIV5 was engineered to express secreted VACV L1R and B5R proteins, two important antigens for neutralization of intracellular mature (IMV) and extracellular enveloped (EEV) virions, respectively. Protection of mice from lethal intranasal VACV challenge required intranasal immunization with PIV5-L1R/B5R in a prime-boost protocol, and correlated with low VACV-induced pathology in the respiratory tract and anti-VACV neutralizing antibody. Mice immunized with PIV5-L1R/B5R showed some disease symptoms following VACV challenge such as loss of weight and hunching, but these symptoms were delayed and less severe than with unimmunized control mice. While immunization with PIV5 expressing B5R alone conferred at least some protection, the most effective immunization included the PIV5 vector expressing L1R alone or in combination with PIV5-B5R. PIV5-L1R/B5R vectors elicited protection from VACV challenge even when CD8+ cells were depleted, but not in the case of mice that were defective in B cell production. Mice were protected from VACV challenge out to at least 1.5 years after immunization with PIV5-L1R/B5R vectors, and showed significant levels of anti-VACV neutralizing antibodies. These results demonstrate the potential for PIV5-based vectors to provide long lasting protection against complex human respiratory pathogens such as VACV, but also highlight the need to understand mechanisms for the generation of strong immune responses against poorly immunogenic viral proteins., (Copyright © 2011 Elsevier Inc. All rights reserved.)
- Published
- 2011
- Full Text
- View/download PDF
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