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1.  C. elegans Demonstrates Distinct Behaviors within a Fixed and Uniform Electric Field 
PLoS ONE  2016;11(3):e0151320.
C. elegans will orient and travel in a straight uninterrupted path directly towards the negative pole of a DC electric field. We have sought to understand the strategy worms use to navigate to the negative pole in a uniform electric field that is fixed in both direction and magnitude. We examined this behavior by quantifying three aspects of electrotaxis behavior in response to different applied field strengths: the mean approach trajectory angles of the animals’ tracks, turning behavior (pirouettes) and average population speeds. We determined that C. elegans align directly to the negative pole of an electric field at sub-preferred field strength and alter approach trajectories at higher field strengths to maintain taxis within a preferred range we have calculated to be ~ 5V/cm. We sought to identify the sensory neurons responsible for the animals’ tracking to a preferred field strength. eat-4 mutant animals defective in glutamatergic signaling of the amphid sensory neurons are severely electrotaxis defective and ceh-36 mutant animals, which are defective in the terminal differentiation of two types of sensory neurons, AWC and ASE, are partially defective in electrotaxis. To further elucidate the role of the AWC neurons, we examined the role of each of the pair of AWC neurons (AWCOFF and AWCON), which are functionally asymmetric and express different genes. nsy-5/inx-19 mutant animals, which express both neurons as AWCOFF, are severely impaired in electrotaxis behavior while nsy-1 mutants, which express both neurons as AWCON, are able to differentiate field strengths required for navigation to a specific field strength within an electric field. We also tested a strain with targeted genetic ablation of AWC neurons and found that these animals showed only slight disruption of directionality and turning behavior. These results suggest a role for AWC neurons in which complete loss of function is less disruptive than loss of functional asymmetry in electrotaxis behavior within a uniform fixed field.
PMCID: PMC4801214  PMID: 26998749
2.  An ecological approach to measuring the evolutionary consequences of gene flow from crops to wild or weedy relatives1 
Applications in Plant Sciences  2016;4(3):apps.1500114.
Premise of the study:
Agricultural practices routinely create opportunities for crops to hybridize with wild relatives, leading to crop gene introgression into wild genomes. Conservationists typically worry this introgression could lead to genetic homogenization of wild populations, over and above the central concern of transgene escape. Alternatively, viewing introgression as analogous to species invasion, we suggest that increased genetic diversity may likewise be an undesirable outcome.
Here, we compare the sensitivity of conventional population genetic metrics with species diversity indices as indicators of the impact of gene flow on genetic diversity. We illustrate this novel approach using multilocus genotype data (12 allozyme loci) from 10 wild (Beta vulgaris subsp. maritima) and eight putative crop–wild hybrid beet populations (B. vulgaris subsp. vulgaris × B. vulgaris subsp. maritima) scattered throughout Europe.
Conventional population genetic metrics mostly failed to detect shifts in genetic composition of putative hybrid populations. By contrast, species diversity indices unambiguously revealed increased genetic diversity in putative hybrid populations.
We encourage other workers to explore the utility of our more sensitive approach for risk assessment prior to the release of transgenic crops, with a view toward widespread adoption of our method in studies aimed at detecting allelic invasion.
PMCID: PMC4795919  PMID: 27011898
Beta vulgaris; biotic homogenization; crop–wild gene flow; genetic diversity; genetic homogenization; genetically engineered plants; risk assessment
3.  The efficacy of a new translational treatment for persecutory delusions: study protocol for a randomised controlled trial (The Feeling Safe Study) 
Trials  2016;17:134.
Persecutory delusions (strong unfounded fears that others intend harm to the person) occur in more than 70 % of the patients diagnosed with schizophrenia. This major psychotic experience is a key clinical target, for which substantial improvement in treatment is needed. Our aim is to use advances in theoretical understanding to develop a much more efficacious treatment that leads to recovery in at least 50 % of people with persistent persecutory delusions. Our cognitive conceptualisation is that persecutory delusions are threat beliefs, developed in the context of genetic and environmental risk, maintained by a number of psychological processes including excessive worry, low self-confidence, intolerance of anxious affect and other internal anomalous experiences, reasoning biases, and safety-seeking strategies. The clinical implication is that safety has to be relearned, by entering the feared situations after reduction of the influence of the maintenance factors. We have been individually evaluating modules targeting causal factors. These will now be tested together as a full treatment, called The Feeling Safe Programme. The treatment is modular, personalised, and includes patient preference. We will test whether the new treatment leads to greater recovery in persistent persecutory delusions, psychological well-being, and activity levels compared to befriending (that is, controlling for therapist attention).
The Feeling Safe Study is a parallel group randomised controlled trial for 150 patients who have persecutory delusions despite previous treatment in mental health services. Patients will be randomised (1:1 ratio) to The Feeling Safe Programme or befriending (both provided in 20 sessions over 6 months). Standard care will continue as usual. Online randomisation will use a permuted blocks algorithm, with randomly varying block size, stratified by therapist. Assessments, by a rater blind to allocation, will be conducted at 0, 6 (post treatment), and 12 months. The primary outcome is the level of delusional conviction at 6 months. Secondary outcomes include levels of psychological well-being, suicidal ideation, and activity. All main analyses will be intention-to-treat. The trial is funded by the NHS National Institute for Health Research.
The Feeling Safe study will provide a Phase II evaluation of a new targeted translational psychological treatment for persecutory delusions.
Trial registration
Current Controlled Trials ISRCTN18705064 (registered 11 November 2015).
PMCID: PMC4788840  PMID: 26969128
Paranoia; persecutory delusions; schizophrenia; psychosis; cognitive therapy
4.  Marriage, Social Networks, and Health at Older Ages 
Journal of population ageing  2015;8(1-2):7-25.
PMCID: PMC4531842  PMID: 26279707
5.  α,β-Dehydro-Dopa: A Hidden Participant in Mussel Adhesion 
Biochemistry  2016;55(5):743-750.
Dopa (L-3,4-dihydroxyphenylalanine) is a key chemical signature of mussel adhesive proteins, but its susceptibility to oxidation has limited mechanistic investigations as well as practical translation to wet adhesion technology. To investigate peptidyl-Dopa oxidation, the highly diverse chemical environment of Dopa in mussel adhesive proteins was simplified to a peptidyl-Dopa analogue, N-acetyl-Dopa ethyl ester. On the basis of cyclic voltammetry and UV–vis spectroscopy, the Dopa oxidation product at neutral to alkaline pH was shown to be α,β-dehydro-Dopa (ΔD), a vinylcatecholic tautomer of Dopa-quinone. ΔD exhibited an adsorption capacity on TiO2 20-fold higher than that of the Dopa homologue in the quartz crystal microbalance. Cyclic voltammetry confirmed the spontaneity of ΔD formation in mussel foot protein 3F at neutral pH that is coupled to a change in protein secondary structure from random coil to β-sheet. A more complete characterization of ΔD reactivity adds a significant new perspective to mussel adhesive chemistry and the design of synthetic bioinspired adhesives.
Graphical abstract
PMCID: PMC4760353  PMID: 26745013
6.  Estimation of Cell-Type Composition Including T and B Cell Subtypes for Whole Blood Methylation Microarray Data 
DNA methylation levels vary markedly by cell-type makeup of a sample. Understanding these differences and estimating the cell-type makeup of a sample is an important aspect of studying DNA methylation. DNA from leukocytes in whole blood is simple to obtain and pervasive in research. However, leukocytes contain many distinct cell types and subtypes. We propose a two-stage model that estimates the proportions of six main cell types in whole blood (CD4+ T cells, CD8+ T cells, monocytes, B cells, granulocytes, and natural killer cells) as well as subtypes of T and B cells. Unlike previous methods that only estimate overall proportions of CD4+ T cell, CD8+ T cells, and B cells, our model is able to estimate proportions of naïve, memory, and regulatory CD4+ T cells as well as naïve and memory CD8+ T cells and naïve and memory B cells. Using real and simulated data, we are able to demonstrate that our model is able to reliably estimate proportions of these cell types and subtypes. In studies with DNA methylation data from Illumina's HumanMethylation450k arrays, our estimates will be useful both for testing for associations of cell type and subtype composition with phenotypes of interest as well as for adjustment purposes to prevent confounding in epigenetic association studies. Additionally, our method can be easily adapted for use with whole genome bisulfite sequencing (WGBS) data or any other genome-wide methylation data platform.
PMCID: PMC4757643  PMID: 26925097
DNA methylation; whole blood; T cell subtypes; B cell subtypes; epigenetics; deconvolution; cell-type composition
7.  C9orf72 ablation in mice does not cause motor neuron degeneration or motor deficits 
Annals of Neurology  2015;78(3):426-438.
How hexanucleotide (GGGGCC) repeat expansions in C9ORF72 cause amyotrophic lateral sclerosis (ALS) remains poorly understood. Both gain‐ and loss‐of‐function mechanisms have been proposed. Evidence supporting these mechanisms in vivo is, however, incomplete. Here we determined the effect of C9orf72 loss‐of‐function in mice.
We generated and analyzed a conditional C9orf72 knockout mouse model. C9orf72fl/fl mice were crossed with Nestin‐Cre mice to selectively remove C9orf72 from neurons and glial cells. Immunohistochemistry was performed to study motor neurons and neuromuscular integrity, as well as several pathological hallmarks of ALS, such as gliosis and TDP‐43 mislocalization. In addition, motor function and survival were assessed.
Neural‐specific ablation of C9orf72 in conditional C9orf72 knockout mice resulted in significantly reduced body weight but did not induce motor neuron degeneration, defects in motor function, or altered survival.
Our data suggest that C9orf72 loss‐of‐function, by itself, is insufficient to cause motor neuron disease. These results may have important implications for the development of therapeutic strategies for C9orf72‐associated ALS. Ann Neurol 2015;78:426–438
PMCID: PMC4744979  PMID: 26044557
8.  Cross-sectional and longitudinal associations between the active vitamin D metabolite (1,25 dihydroxyvitamin D) and haemoglobin levels in older Australian men: the Concord Health and Ageing in Men Project 
Age  2015;37(1):8.
Anaemia and low 25 hydroxyvitamin D (25D) and 1,25 dihydroxyvitamin D (1,25D) levels are common in older people and may adversely affect morbidity and mortality. While there is some evidence for an association between low serum 25D levels and anaemia, there are limited studies among community-dwelling older people. In addition, the relationship between anaemia and the active vitamin D metabolite, 1,25D, has not been investigated. The aim of this study was to examine the associations between serum 25D and 1,25D with anaemia in community-living men aged ≥70 years. Population-based, cross-sectional analysis of the baseline phase and longitudinal analysis of the Concord Health and Ageing in Men Project (CHAMP), a large epidemiological study conducted in Sydney among men aged 70 years and older, were performed; 1666 men were seen at baseline (2005–2007), 1314 men at a 2-year follow-up (2007–2009) and 917 at a 5-year follow-up (2012–2013). The main outcome measurement was haemoglobin levels as a continuous measure. Covariates included 25D and 1,25D, estimated glomerular filtration rate, demographic information, lifestyle measures, health conditions and medication information. The prevalence of anaemia (Hb < 13.0 g/dL, WHO definition) was 14.6 %. In cross-sectional analysis, serum 25D concentrations were positively associated with haemoglobin levels in unadjusted analysis (β value 0.004; 95 % confidence interval (CI) 0.0009, 0.007; p = 0.01), but the associations were no longer significant after multivariate adjustment. The association between 1,25D levels and haemoglobin levels was significant in unadjusted analysis (β value 0.003; 95 % CI 0.002, 0.004; p < 0.0001) and remained significant in adjusted analysis (β value 0.001; 95 % CI 0.004, 0.003; p = 0.01). Serum 1,25D (but not 25D) levels at baseline were significantly associated with changes in haemoglobin over 2 and 5 years in unadjusted (β value 0.002; 95 % CI 0.0009, 0.003; p < 0.0001) and in fully adjusted analyses (β value 0.001; 95 % CI 0.0004, 0.002; p = 0.001). Serum 1,25D, but not 25D, concentrations are independently associated with haemoglobin levels in older men in both cross-sectional and longitudinal analyses. This raises the question whether vitamin D metabolites may influence anaemia states, mediated through different biological pathways, or represent a time-dependent biomarker of chronic ill health.
PMCID: PMC4315774  PMID: 25649710
Vitamin D; Calcitriol; Anaemia older men; Population study
9.  Development and Validation of the Comprehensive Health Activities Scale: A New Approach to Health Literacy Measurement 
Journal of health communication  2014;20(2):157-164.
Current health literacy measures have been criticized for solely measuring reading and numeracy skills when a broader set of skills is necessary for making informed health decisions, especially when information is often conveyed verbally and through multimedia video. We devised nine health tasks and a corresponding 190 item assessment to more comprehensively measure health literacy skills. A sample of 826 participants age 55-74 recruited from an academic General Internal Medicine practice and three Federally Qualified Health Centers in Chicago, Illinois completed the assessment. Items were reduced using hierarchical factor analysis and item response theory resulting in the 45-item Comprehensive Health Activities Scale (CHAS). All 45 items loaded on one general latent trait and the resulting scale demonstrated high reliability and strong construct validity using measures of health literacy and global cognitive functioning. The predictive validity of the CHAS using self-reported general, physical, and mental health status was comparable to or better than widely used measures of health literacy, depending on the outcome. Despite comprehensively measuring health literacy skills, items in the CHAS supported one primary construct. With similar psychometric properties, current measures may be adequate, depending on the purpose of the assessment.
PMCID: PMC4346471  PMID: 25375025
10.  Insomnia Symptoms and Actigraph-Estimated Sleep Characteristics in a Nationally Representative Sample of Older Adults 
Reports of insomnia symptoms are common among the elderly. However, little is known about the relationship between insomnia symptoms and objective assessments of sleep in the general population of older adults. We assessed concordance between insomnia symptoms and actigraphic sleep characteristics in a nationally representative sample of older Americans.
In a national probability sample of 727 adults aged 62–91 years in 2010–2011 from the National Social Life, Health, and Aging Project, respondents were asked how often they (a) feel rested when they wake up, (b) have trouble falling asleep, (c) have trouble with waking up during the night, and (d) have trouble waking up too early and not being able to fall asleep again. Responses to these questions were compared to sleep characteristics estimated from three nights of actigraphy for the same individuals. Statistical analyses were adjusted for age, gender, race and ethnicity, income, assets, and education.
Feeling rested (Question (a), above) was not correlated with any actigraphy-estimated sleep characteristics. Questions (b)–(d) each had several significant correlations with the actigraphy metrics, but generally not with the specific objective sleep characteristics that each question intended to reference. In some cases, the associations were not in the expected direction.
Although three of four questions about insomnia symptoms were significantly associated with objectively estimated sleep characteristics, responses seem to be general indicators of sleep quality rather than reports of specific sleep characteristics.
PMCID: PMC4366601  PMID: 25199910
Epidemiology; Geriatric assessment; Sleep.
11.  Reduction of the Powerful Greenhouse Gas N2O in the South-Eastern Indian Ocean 
PLoS ONE  2016;11(1):e0145996.
Nitrous oxide (N2O) is a powerful greenhouse gas and a key catalyst of stratospheric ozone depletion. Yet, little data exist about the sink and source terms of the production and reduction of N2O outside the well-known oxygen minimum zones (OMZ). Here we show the presence of functional marker genes for the reduction of N2O in the last step of the denitrification process (nitrous oxide reductase genes; nosZ) in oxygenated surface waters (180–250 O2 μ in the south-eastern Indian Ocean. Overall copy numbers indicated that nosZ genes represented a significant proportion of the microbial community, which is unexpected in these oxygenated waters. Our data show strong temperature sensitivity for nosZ genes and reaction rates along a vast latitudinal gradient (32°S-12°S). These data suggest a large N2O sink in the warmer Tropical waters of the south-eastern Indian Ocean. Clone sequencing from PCR products revealed that most denitrification genes belonged to Rhodobacteraceae. Our work highlights the need to investigate the feedback and tight linkages between nitrification and denitrification (both sources of N2O, but the latter also a source of bioavailable N losses) in the understudied yet strategic Indian Ocean and other oligotrophic systems.
PMCID: PMC4723335  PMID: 26800249
13.  Real-Time PCR Assay for the Identification of the Brown Marmorated Stink Bug (Halyomorpha halys) 
The brown marmorated stink bug, Halyomorpha halys (Hemiptera: Pentatomidae), is a gregarious crop pest that has rapidly spread across the world in the last two decades. It is an excellent hitchhiker species, especially as an over-wintering adult. During this period it is often associated with non-biological commodities such as shipping containers and machinery that travel long distances. Inadequate identification keys and similarity to common species has assisted its spread across Europe, while accurate identification from immature stages or eggs is not possible. We developed a real-time TaqMan PCR assay for the accurate and sensitive detection of the brown marmorated stink bug from all life stages. The assay performance against required diagnostic criterion and within a quarantine framework are described.
PMCID: PMC4767901  PMID: 26955631
qPCR; invasive species; diagnostic test; Pentatomidae; biosecurity
14.  Familial frontotemporal dementia with amyotrophic lateral sclerosis and a shared haplotype on chromosome 9p 
Journal of neurology  2010;258(4):647-655.
Families with autosomal dominant frontotemporal dementia and amyotrophic lateral sclerosis (FTD/ALS) have previously been linked to a locus on chromosome 9p21. We describe the clinical phenotype and pathology of a large family with autosomal dominant FTD/ALS with nine affected members originating from Gwent in South Wales, UK. We also further refine the locus on chromosome 9p21 using a haplotype sharing approach and assess heterogeneity in 9p21 linked families. Within this family, affected individuals present with either FTD or ALS or both diseases simultaneously. In addition there was marked phenotypic variation including ataxia, Parkinsonism, psychosis and visuo-spatial cognitive deficits. The pathological features of the three cases described were consistent with type 2 FTD pathology, as previously reported in similar families. However, we also report distinctive cerebellar and glial pathology and a significant proportion of TDP-43 negative inclusions. No mutations in known genes for FTD or ALS were found. We identified a large 4.8-megabase haplotype on chromosome 9p21, which was shared by all affected family members. This haplotype overlaps and limits the previously reported FTD/ALS linkage region on chromosome 9p21. Sequencing of this region did not identify any evidence of a pathogenic exonic mutation. This suggests that the pathogenic change affects non-coding DNA and that the disease is caused by variation in gene or protein expression.
PMCID: PMC4696389  PMID: 21072532
Frontotemporal dementia; Amyotrophic lateral sclerosis; Mendelian; Chromosome 9
15.  Bridging Adhesion of Mussel-Inspired Peptides: Role of Charge, Chain Length, and Surface Type 
Langmuir  2014;31(3):1105-1112.
The 3,4-dihydroxyphenylalanine (Dopa)-containing proteins of marine mussels provide attractive design paradigms for engineering synthetic polymers that can serve as high performance wet adhesives and coatings. Although the role of Dopa in promoting adhesion between mussels and various substrates has been carefully studied, the context by which Dopa mediates a bridging or nonbridging macromolecular adhesion to surfaces is not understood. The distinction is an important one both for a mechanistic appreciation of bioadhesion and for an intelligent translation of bioadhesive concepts to engineered systems. On the basis of mussel foot protein-5 (Mfp-5; length 75 res), we designed three short, simplified peptides (15–17 res) and one relatively long peptide (30 res) into which Dopa was enzymatically incorporated. Peptide adhesion was tested using a surface forces apparatus. Our results show that the short peptides are capable of weak bridging adhesion between two mica surfaces, but this adhesion contrasts with that of full length Mfp-5, in that (1) while still dependent on Dopa, electrostatic contributions are much more prominent, and (2) whereas Dopa surface density remains similar in both, peptide adhesion is an order of magnitude weaker (adhesion energy Ead ∼ −0.5 mJ/m2) than full length Mfp-5 adhesion. Between two mica surfaces, the magnitude of bridging adhesion was approximately doubled (Ead ∼ −1 mJ/m2) upon doubling the peptide length. Notably, the short peptides mediate much stronger adhesion (Ead ∼ −3.0 mJ/m2) between mica and gold surfaces, indicating that a long chain length is less important when different interactions are involved on each of the two surfaces.
PMCID: PMC4310636  PMID: 25540823
16.  Marriage, Relationship Quality, and Sleep among U.S. Older Adults 
Sleep is a restorative behavior essential for health. Poor sleep has been linked to adverse health outcomes among older adults, however, we know little about the social processes that affect sleep. Using innovative actigraphy data from the National Social Life, Health and Aging Project (N=727), we considered the role of marriage, positive marital relationship support, and negative marital relationship strain on older adults’ (aged 62–90) self-reported and actigraph-measured sleep characteristics. We found that married older adults had better actigraph-estimated but not self-reported sleep characteristics than the unmarried. However, among the married, those who reported more negative aspects of their marital relationship reported more insomnia symptoms, with the association reduced when psychosocial characteristics were added to the model. The married who reported more positive aspects of their marital relationship showed better actigraph-estimated sleep characteristics; taking characteristics of the physical and mental health and home environment into account reduced this association.
PMCID: PMC4677485  PMID: 26272988
17.  High-performance mussel-inspired adhesives of reduced complexity 
Nature Communications  2015;6:8663.
Despite the recent progress in and demand for wet adhesives, practical underwater adhesion remains limited or non-existent for diverse applications. Translation of mussel-inspired wet adhesion typically entails catechol functionalization of polymers and/or polyelectrolytes, and solution processing of many complex components and steps that require optimization and stabilization. Here we reduced the complexity of a wet adhesive primer to synthetic low-molecular-weight catecholic zwitterionic surfactants that show very strong adhesion (∼50 mJ m−2) and retain the ability to coacervate. This catecholic zwitterion adheres to diverse surfaces and self-assembles into a molecularly smooth, thin (<4 nm) and strong glue layer. The catecholic zwitterion holds particular promise as an adhesive for nanofabrication. This study significantly simplifies bio-inspired themes for wet adhesion by combining catechol with hydrophobic and electrostatic functional groups in a small molecule.
Mussels use strong filaments to adhere to rocks, preventing them from being swept away in strong currents. Here, the authors borrow and simplify chemistries from the mussel foot to create a one component adhesive system which holds potential for employment in nanofabrication protocols.
PMCID: PMC4667698  PMID: 26478273
18.  Multiple, but not traditional risk factors predict mortality in older people: the concord health and ageing in men project 
Age  2014;36(6):9732.
This study aims to identify the common risk factors for mortality in community-dwelling older men. A prospective population-based study was conducted with a median of 6.7 years of follow-up. Participants included 1705 men aged ≥70 years at baseline (2005–2007) living in the community in Sydney, Australia. Demographic information, lifestyle factors, health status, self-reported history of diseases, physical performance measures, blood pressure, height and weight, disability (activities of daily living (ADL) and instrumental ADLs, instrumental ADLs (IADLs)), cognitive status, depressive symptoms and blood analyte measures were considered. Cox regression analyses were conducted to model predictors of mortality. During follow-up, 461 men (27 %) died. Using Cox proportional hazards model, significant predictors of mortality included in the final model (p < 0.05) were older age, body mass index < 20 kg m2, high white cell count, anaemia, low albumin, current smoking, history of cancer, history of myocardial infarction, history of congestive heart failure, depressive symptoms and ADL and IADL disability and impaired chair stands. We found that overweight and obesity and/or being a lifelong non-drinker of alcohol were protective against mortality. Compared to men with less than or equal to one risk factor, the hazard ratio in men with three risk factors was 2.5; with four risk factors, it was 4.0; with five risk factors, it was 4.9; and for six or more risk factors, it was 11.4, respectively. We have identified common risk factors that predict mortality that may be useful in making clinical decisions among older people living in the community. Our findings suggest that, in primary care, screening and management of multiple risk factors are important to consider for extending survival, rather than simply considering individual risk factors in isolation. Some of the “traditional” risk factors for mortality in a younger population, including high blood pressure, hypercholesterolaemia, overweight and obesity and diabetes, were not independent predictors of mortality in this population of older men.
PMCID: PMC4234745  PMID: 25403157
Mortality; Sociodemographic; Economic and lifestyle factors; Health conditions; Physical function; Disability
19.  Assessment of Surgical Effects on Patients with Obstructive Sleep Apnea Syndrome Using Computational Fluid Dynamics Simulations 
Obstructive sleep apnea syndrome is one of the most common sleep disorders. To treat patients with this health problem, it is important to detect the severity of this syndrome and occlusion sites in each patient. The goal of this study is to test the hypothesis that the cure of obstructive sleep apnea syndrome by maxillomandibular advancement surgery can be predicted by analyzing the effect of anatomical airway changes on the pressure effort required for normal breathing using a high-fidelity, 3-D numerical model. The employed numerical model consists of: 1) 3-D upper airway geometry construction from patient-specific computed tomographic scans using an image segmentation technique, 2) mixed-element mesh generation of the numerically constructed airway geometry for discretizing the domain of interest, and 3) computational fluid dynamics simulations for predicting the flow field within the airway and the degree of severity of breathing obstruction. In the present study, both laminar and turbulent flow simulations were performed to predict the flow field in the upper airway of the selected patients before and after maxillomandibular advancement surgery. Patients of different body mass indices were also studied to assess their effects. The numerical results were analyzed to evaluate the pressure gradient along the upper airway. The magnitude of the pressure gradient is regarded as the pressure effort required for breathing, and the extent of reduction of the pressure effort is taken to measure the success of the surgery. The description of the employed numerical model, numerical results from simulations of various patients, and suggestion for future work are detailed in this paper.
PMCID: PMC4269252  PMID: 25530663
Obstructive Sleep Apnea Syndrome (OSAS); sleep apnea; Computational Fluid Dynamics (CFD); mesh generation; Maxillomandibular Advancement (MMA)
20.  Interpretation of ambiguity: Differences between children and adolescents with and without an anxiety disorder 
Journal of Affective Disorders  2015;188:194-201.
Theory and treatment of anxiety disorders in young people are commonly based on the premise that interpretation biases found in anxious adults are also found in children and adolescents. Although there is some evidence that this may be the case, studies have not typically taken age into account, which is surprising given the normative changes in cognition that occur throughout childhood. The aim of the current study was to identify whether associations between anxiety disorder status and interpretation biases differed in children and adolescents.
The responses of children (7–10 years) and adolescents (13–16 years) with and without anxiety disorders (n=120) were compared on an ambiguous scenarios task.
Children and adolescents with an anxiety disorder showed significantly higher levels of threat interpretation and avoidant strategies than non-anxious children and adolescents. However, age significantly moderated the effect of anxiety disorder status on interpretation of ambiguity, in that adolescents with anxiety disorders showed significantly higher levels of threat interpretation and associated negative emotion than non-anxious adolescents, but a similar relationship was not observed among children.
The findings suggest that theoretical accounts of interpretation biases in anxiety disorders in children and adolescents should distinguish between different developmental periods. For both ages, treatment that targets behavioral avoidance appears warranted. However, while adolescents are likely to benefit from treatment that addresses interpretation biases, there may be limited benefit for children under the age of ten.
•Cognitive theories of anxiety emphasize the role of interpretation bias.•We examine interpretation bias in anxious and non-anxious children and adolescents.•Anxious adolescents show more threat interpretation than non-anxious adolescents.•Anxious and non-anxious children show similar levels of threat interpretation.•Theories should distinguish between different developmental periods.
PMCID: PMC4641870  PMID: 26363617
Anxiety/anxiety disorders; Child/adolescent; Cognition
21.  Mussel Coating Protein-Derived Complex Coacervates Mitigate Frictional Surface Damage 
The role of friction in the functional performance of biomaterial interfaces is widely reckoned to be critical and complicated but poorly understood. To better understand friction forces, we investigated the natural adaptation of the holdfast or byssus of mussels that live in high-energy surf habitats. As the outermost covering of the byssus, the cuticle deserves particular attention for its adaptations to frictional wear under shear. In this study, we coacervated one of three variants of a key cuticular component, mussel foot protein 1, mfp-1 [(1) Mytilus californianus mcfp-1, (2) rmfp-1, and (3) rmfp-1-Dopa], with hyaluronic acid (HA) and investigated the wear protection capabilities of these coacervates to surfaces (mica) during shear. Native mcfp-1/HA coacervates had an intermediate coefficient of friction (μ ∼0.3) but conferred excellent wear protection to mica with no damage from applied loads, F⊥, as high as 300 mN (pressure, P, > 2 MPa). Recombinant rmfp-1/HA coacervates exhibited a comparable coefficient of friction (μ ∼0.3); however, wear protection was significantly inferior (damage at F⊥ > 60 mN) compared with that of native protein coacervates. Wear protection of rmfp-1/HA coacervates increased 5-fold upon addition of the surface adhesive group 3,4-dihydroxyphenylalanine, (Dopa). We propose a Dopa-dependent wear protection mechanism to explain the differences in wear protection between coacervates. Our results reveal a significant untapped potential for coacervates in applications that require adhesion, lubrication, and wear protection. These applications include artificial joints, contact lenses, dental sealants, and hair and skin conditioners.
PMCID: PMC4642218  PMID: 26618194
biomimetic; adhesion; wear protection; interface; Mytilus californianus foot protein 1; mcfp-1; hyaluronic acid; HA
22.  Relationship Quality and Shared Activity in Marital and Cohabiting Dyads in the National Social Life, Health, and Aging Project, Wave 2 
This paper introduces scales on shared activity and relationship quality for married and partnered older adults using multiple indicators from the second wave of National Social Life, Health, and Aging Project.
We assessed the reliability of the scales using Cronbach’s alpha and the item-total correlation. We conducted exploratory factor analysis to explore the structure of the items and compared the distribution of each scale means by age group and gender.
We found that the relational quality scale has a 2-factor structure, including a positive and negative dimension. The shared activity scale has a 1-factor structure. We found that partnered men show both higher positive and higher negative relationship quality than do partnered women, suggesting that more older men than women experience ambivalent feelings toward their spouse or partner and more women than men have relationships of indifferent quality, with relatively low costs and relatively low benefits.
The separate conceptualization of shared activity and relationship quality provides one way to examine the dynamic nature of marital quality in later life such as the extent to which shared activities among couples promote or detract from relationships’ quality. Analyses for individuals and for dyads are discussed.
PMCID: PMC4303087  PMID: 25123690
Dyads; Relationship quality; Shared activity.
23.  Assessment of Sleep in the National Social Life, Health, and Aging Project 
The relationship of sleep to health has been an active area of research in recent years, and the National Social Life, Health, and Aging Project (NSHAP) expanded sleep data collection in Wave 2 with enhanced core questions and a novel sleep module that included an objective measure of sleep duration and quality.
A randomly selected one-third of Wave 2 participants and their spouses or coresident partners were invited to participate in the sleep module. Objective sleep data were collected using wrist actigraphy, an accelerometer that records an integrated measure of motion over short epochs (15 s each). This information is stored and subsequently analyzed to determine sleep and wake periods by epoch. Individuals were instructed to wear the actiwatches for 72hr. Several sleep parameters were derived from the accelerometer. Individuals concurrently kept a sleep diary.
Sleep actigraphy data were successfully collected from 780 individuals. Many of the survey-based and the actigraph-estimated sleep parameters varied by age and gender. However, age and gender patterns often differed for sleep characteristics that were both asked and measured, such as sleep duration.
The survey and actigraphy data provide different information about sleep characteristics. The opportunity to examine actigraph-estimated sleep characteristics in a nationally representative sample of older adults allows novel analyses of the associations of sleep parameters with social and health data.
PMCID: PMC4303091  PMID: 25360013
Actigraphy; Sleep; Sleep duration; Sleep quality.
24.  Sexuality and Physical Contact in National Social Life, Health, and Aging Project Wave 2 
Wave 2 of the National Social Life, Health, and Aging Project (NSHAP) includes new measures of sexual interest and behavior, as well as new measures of the context of sexual experience and the frequency and appeal of physical contact. This is the first time many of these constructs have been measured in a nationally representative sample.
We describe the new measures and compare the distributions of each across gender and age groups, in some cases by partnership status.
Two components of sexuality decrease with age among both men and women: frequency of finding an unknown person sexually attractive and receptivity to a partner’s sexual overtures. In contrast, the inclination to make one’s self sexually attractive to others was a more complicated function of partner status, gender, and age: partnered women and unpartnered men made the most effort, with the more effortful gender’s effort decreasing with age. Both men and women find nonsexual physical contact appealing but sexual physical contact is more appealing to men than women. Finally, two fifths of men and women report dissatisfaction with their partner’s frequency of caring behaviors that make later sexual interactions pleasurable, and a fifth of women and a quarter of men who had vaginal sex in the past year report dissatisfaction with amount of foreplay.
These data offer the opportunity to characterize sexual motivation in older adulthood more precisely and richly and to examine how the context of sexual experience and the nonsexual aspects of physical intimacy correlate with sexual behavior, enjoyment, and problems.
PMCID: PMC4303093  PMID: 25360027
Caring touch; Physical contact; Sex behavior; Sexual interest; Sexuality.
25.  Geriatric Syndromes and Functional Status in NSHAP: Rationale, Measurement, and Preliminary Findings 
The geriatric functional measures and syndromes collected 5 years apart in Waves 1 and 2 of the National Social Life, Health, and Aging Project (NSHAP) data set included: difficulty with activities of daily living and instrumental activities of daily living, the timed up and go, a 3-m timed walk, repeated chair stands, self-reported physical activity, accelerometry-assessed (in)activity, falls, fractures, and frailty. The purpose of this paper was to describe the data collection methods and report preliminary population estimates for each measures.
Frequencies, means, or medians were estimated for each measure stratified by age and gender, using the age-eligible samples in Wave 1 (n = 3,005) and Wave 2 (n = 3,196). An adapted phenotypic frailty scale was constructed in the sample common to both waves (n = 2,261). Changes over 5 years were reported for four measures common to both waves.
The functional measures worsened with age (p < .001). The syndromes were more prevalent with age except “all fractures” (p value range < .001–.03). Functional measures were worse among females than males except chair stand performance and the accelerometry-assessed (in)activity measures (p value range < .001–.01). The syndromes were more common among females than males except Wave 2 falls and Wave 2 hip fractures (p value range < .001–.03). Changes from Wave 1 to 2 revealed 11.5%–25.2% of individuals reported better health and 21.3%–44.7% reported worse health.
The NSHAP provides a comprehensive assessment of geriatric health. Our findings are consistent with the literature and support the construct of the study measures.
PMCID: PMC4303102  PMID: 25360019
Accelerometry; Falls; Fracture; Frailty; Functional assessment; Gait; Older adults; Physical activity.

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