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1.  Inter-rater Agreement for Diagnoses of Epilepsy in Pregnant Women 
Epilepsy & behavior : E&B  2013;27(1):148-153.
We report on inter-rater agreement in assessing the types of seizures exhibited by one hundred mothers ascertained in a study of the teratogenicity of maternal epilepsy and antiepileptic drugs. A summary of each woman’s medical record, and a one-page report of her responses to questions about her epilepsy, were reviewed independently by six neurologists, three in pediatric neurology and three in adult neurology. Agreement was measured by the kappa statistic and log-linear modeling techniques. The adult neurologists agreed with each other 59 percent of the time, with agreement higher when all three used information from the patients’ records, such as an EEG, rather than when depending on the woman’s responses to questions about her epilepsy. Pediatric neurologists agreed with each other 44% of the time and tended to rely more heavily, than adult neurologists, on information in the patients’ records, such as an EEG or a prior diagnosis.
PMCID: PMC3602402  PMID: 23416992
types of seizures; adult and pediatric neurologists; log linear modeling
2.  A Genome-Wide Metabolic QTL Analysis in Europeans Implicates Two Loci Shaped by Recent Positive Selection 
PLoS Genetics  2011;7(9):e1002270.
We have performed a metabolite quantitative trait locus (mQTL) study of the 1H nuclear magnetic resonance spectroscopy (1H NMR) metabolome in humans, building on recent targeted knowledge of genetic drivers of metabolic regulation. Urine and plasma samples were collected from two cohorts of individuals of European descent, with one cohort comprised of female twins donating samples longitudinally. Sample metabolite concentrations were quantified by 1H NMR and tested for association with genome-wide single-nucleotide polymorphisms (SNPs). Four metabolites' concentrations exhibited significant, replicable association with SNP variation (8.6×10−11
Author Summary
Physiological concentrations of metabolites—small molecules involved in biochemical processes in living systems—can be measured and used to diagnose and predict disease states. A common goal is to detect and clinically exploit statistical differences in metabolite concentrations between diseased and healthy individuals. As a basis for the design and interpretation of case-control studies, it is useful to have a characterization of metabolic diversity amongst healthy individuals, some of which stems from inter-individual genetic variation. When a single genetic locus has a sufficiently strong effect on metabolism, its genomic position can be determined by collecting metabolite concentration data and genome-wide genotype data on a set of individuals and searching for associations between the two data sets—a so-called metabolite quantitative trait locus (mQTL) study. By so tracing mQTLs, we can identify the genetic drivers of metabolism, characterize how the nature or quantity of the corresponding expressed protein(s) feeds forward to influence metabolite levels, and specify disease-predictive models that incorporate mutual dependence amongst genetics, environment, and metabolism.
PMCID: PMC3169529  PMID: 21931564
A comprehensive variation map of the human metabolome identifies genetic and stable-environmental sources as major drivers of metabolite concentrations. The data suggest that sample sizes of a few thousand are sufficient to detect metabolite biomarkers predictive of disease.
We designed a longitudinal twin study to characterize the genetic, stable-environmental, and longitudinally fluctuating influences on metabolite concentrations in two human biofluids—urine and plasma—focusing specifically on the representative subset of metabolites detectable by 1H nuclear magnetic resonance (1H NMR) spectroscopy.We identified widespread genetic and stable-environmental influences on the (urine and plasma) metabolomes, with (30 and 42%) attributable on average to familial sources, and (47 and 60%) attributable to longitudinally stable sources.Ten of the metabolites annotated in the study are estimated to have >60% familial contribution to their variation in concentration.Our findings have implications for the design and interpretation of 1H NMR-based molecular epidemiology studies. On the basis of the stable component of variation quantified in the current paper, we specified a model of disease association under which we inferred that sample sizes of a few thousand should be sufficient to detect disease-predictive metabolite biomarkers.
Metabolites are small molecules involved in biochemical processes in living systems. Their concentration in biofluids, such as urine and plasma, can offer insights into the functional status of biological pathways within an organism, and reflect input from multiple levels of biological organization—genetic, epigenetic, transcriptomic, and proteomic—as well as from environmental and lifestyle factors. Metabolite levels have the potential to indicate a broad variety of deviations from the ‘normal' physiological state, such as those that accompany a disease, or an increased susceptibility to disease. A number of recent studies have demonstrated that metabolite concentrations can be used to diagnose disease states accurately. A more ambitious goal is to identify metabolite biomarkers that are predictive of future disease onset, providing the possibility of intervention in susceptible individuals.
If an extreme concentration of a metabolite is to serve as an indicator of disease status, it is usually important to know the distribution of metabolite levels among healthy individuals. It is also useful to characterize the sources of that observed variation in the healthy population. A proportion of that variation—the heritable component—is attributable to genetic differences between individuals, potentially at many genetic loci. An effective, molecular indicator of a heritable, complex disease is likely to have a substantive heritable component. Non-heritable biological variation in metabolite concentrations can arise from a variety of environmental influences, such as dietary intake, lifestyle choices, general physical condition, composition of gut microflora, and use of medication. Variation across a population in stable-environmental influences leads to long-term differences between individuals in their baseline metabolite levels. Dynamic environmental pressures lead to short-term fluctuations within an individual about their baseline level. A metabolite whose concentration changes substantially in response to short-term pressures is relatively unlikely to offer long-term prediction of disease. In summary, the potential suitability of a metabolite to predict disease is reflected by the relative contributions of heritable and stable/unstable-environmental factors to its variation in concentration across the healthy population.
Studies involving twins are an established technique for quantifying the heritable component of phenotypes in human populations. Monozygotic (MZ) twins share the same DNA genome-wide, while dizygotic (DZ) twins share approximately half their inherited DNA, as do ordinary siblings. By comparing the average extent of phenotypic concordance within MZ pairs to that within DZ pairs, it is possible to quantify the heritability of a trait, and also to quantify the familiality, which refers to the combination of heritable and common-environmental effects (i.e., environmental influences shared by twins in a pair). In addition to incorporating twins into the study design, it is useful to quantify the phenotype in some individuals at multiple time points. The longitudinal aspect of such a study allows environmental effects to be decomposed into those that affect the phenotype over the short term and those that exert stable influence.
For the current study, urine and blood samples were collected from a cohort of MZ and DZ twins, with some twins donating samples on two occasions several months apart. Samples were analysed by 1H nuclear magnetic resonance (1H NMR) spectroscopy—an untargeted, discovery-driven technique for quantifying metabolite concentrations in biological samples. The application of 1H NMR to a biological sample creates a spectrum, made up of multiple peaks, with each peak's size quantitatively representing the concentration of its corresponding hydrogen-containing metabolite.
In each biological sample in our study, we extracted a full set of peaks, and thereby quantified the concentrations of all common plasma and urine metabolites detectable by 1H NMR. We developed bespoke statistical methods to decompose the observed concentration variation at each metabolite peak into that originating from familial, individual-environmental, and unstable-environmental sources.
We quantified the variability landscape across all common metabolite peaks in the urine and plasma 1H NMR metabolomes. We annotated a subset of peaks with a total of 65 metabolites; the variance decompositions for these are shown in Figure 1. Ten metabolites' concentrations were estimated to have familial contributions in excess of 60%. The average proportion of stable variation across all extracted metabolite peaks was estimated to be 47% in the urine samples and 60% in the plasma samples; the average estimated familiality was 30% for urine and 42% for plasma. These results comprise the first quantitative variation map of the 1H NMR metabolome. The identification and quantification of substantive widespread stability provides support for the use of these biofluids in molecular epidemiology studies. On the basis of our findings, we performed power calculations for a hypothetical study searching for predictive disease biomarkers among 1H NMR-detectable urine and plasma metabolites. Our calculations suggest that sample sizes of 2000–5000 should allow reliable identification of disease-predictive metabolite concentrations explaining 5–10% of disease risk, while greater sample sizes of 5000–20 000 would be required to identify metabolite concentrations explaining 1–2% of disease risk.
1H Nuclear Magnetic Resonance spectroscopy (1H NMR) is increasingly used to measure metabolite concentrations in sets of biological samples for top-down systems biology and molecular epidemiology. For such purposes, knowledge of the sources of human variation in metabolite concentrations is valuable, but currently sparse. We conducted and analysed a study to create such a resource. In our unique design, identical and non-identical twin pairs donated plasma and urine samples longitudinally. We acquired 1H NMR spectra on the samples, and statistically decomposed variation in metabolite concentration into familial (genetic and common-environmental), individual-environmental, and longitudinally unstable components. We estimate that stable variation, comprising familial and individual-environmental factors, accounts on average for 60% (plasma) and 47% (urine) of biological variation in 1H NMR-detectable metabolite concentrations. Clinically predictive metabolic variation is likely nested within this stable component, so our results have implications for the effective design of biomarker-discovery studies. We provide a power-calculation method which reveals that sample sizes of a few thousand should offer sufficient statistical precision to detect 1H NMR-based biomarkers quantifying predisposition to disease.
PMCID: PMC3202796  PMID: 21878913
biomarker; 1H nuclear magnetic resonance spectroscopy; metabolome-wide association study; top-down systems biology; variance decomposition
Emerging Infectious Diseases  2008;14(6):944-947.
Global surveillance for a novel rhinovirus genotype indicated its association with community outbreaks and pediatric respiratory disease in Africa, Asia, Australia, Europe, and North America. Molecular dating indicates that these viruses have been circulating for at least 250 years.
PMCID: PMC2600308  PMID: 18507910
picornavirus; rhinovirus; HRV-C; multiplex MassTag PCR; lower respiratory tract infection; childhood pneumonia; dispatch
Mand functions for two stimuli (A1 and A2) were trained for 3 children with autism and were then incorporated into two related conditional discriminations (A1-B1/A2 -B2 and B1-C1/B2-C2). Tests were conducted to probe for a derived transfer of mand response functions from A1 and A2 to C1 and C2, respectively. When 1 participant failed to demonstrate derived transfer of mand response functions, transfer training using exemplars was conducted. When participants had demonstrated derived transfer of mand functions, the X1 and X2 tokens that were employed as reinforcers for mand responses were incorporated into two conditional discriminations (X1-Y1/X2-Y2 and Y1-Z1/Y2-Z2). Tests were conducted for derived transfer of reinforcing functions. Finally, tests were conducted to determine if the participants would demonstrate derived manding for the derived reinforcers (present C1 and C2 to mand for Z1 and Z2, respectively). Derived transfer of functions was observed when the sequence of training and testing was reversed (i.e., training and testing reinforcing functions before mand response functions) and when only minimal instructions were provided.
PMCID: PMC1309708  PMID: 16463526
derived transfer; mands; language; autism spectrum disorder; children
Objective: To compare the HMPAO SPECT cerebral perfusion patterns in early and late onset Alzheimer's disease.
Methods: Twenty patients with early onset disease (<65 years) and 44 patients with late onset disease (>65 years) were studied. All patients fulfilled NINCDS-ADRDA clinical criteria and had details of disease severity and length of history at the time of imaging. Technetium-99m HMPAO SPECT brain scans were acquired on a multi-detector gammacamera and analysed visually and with statistical parametric mapping (SPM99).
Results: Patients with early onset disease had significantly greater posterior cortical association area involvement whereas those with late onset disease had significantly greater medial temporal hypoperfusion. These findings were unchanged after controlling for disease severity and length of illness.
Discussion: These functional imaging findings of the differences between early and late onset Alzheimer's disease are supported by published findings that include histopathological and clinical evidence; namely late onset patients tend to present with the characteristic involvement of the medial temporal lobes producing marked memory loss whereas early onset patients present with predominant posterior cortical association area involvement. These age related findings should be borne in mind when clinically diagnosing, and interpreting functional brain imaging studies in, patients with suspected Alzheimer's disease.
PMCID: PMC1738480  PMID: 12754337
The current study aimed to test a Relational Frame Theory (RFT) model of analogical reasoning based on the relating of derived same and derived difference relations. Experiment 1 recorded reaction time measures of similar–similar (e.g., “apple is to orange as dog is to cat”) versus different–different (e.g., “he is to his brother as chalk is to cheese”) derived relational responding, in both speed-contingent and speed-noncontingent conditions. Experiment 2 examined the event-related potentials (ERPs) associated with these two response patterns. Both experiments showed similar–similar responding to be significantly faster than different–different responding. Experiment 2 revealed significant differences between the waveforms of the two response patterns in the left-hemispheric prefrontal regions; different–different waveforms were significantly more negative than similar–similar waveforms. The behavioral and neurophysiological data support the RFT prediction that, all things being equal, similar–similar responding is relationally “simpler” than, and functionally distinct from, different–different analogical responding. The ERP data were fully consistent with findings in the neurocognitive literature on analogy. These findings strengthen the validity of the RFT model of analogical reasoning and supplement the behavior-analytic approach to analogy based on the relating of derived relations.
PMCID: PMC1389775  PMID: 16596974
relating relations; analogy; reasoning; derived relations; humans
Derived equivalence relations, it has been argued, provide a behavioral model of semantic or symbolic meaning in natural language, and thus equivalence relations should possess properties that are typically associated with semantic relations. The present study sought to test this basic postulate using semantic priming. Across three experiments, participants were trained and tested in two 4-member equivalence relations using word-like nonsense words. Participants also were exposed to a single- or two-word lexical decision task, and both direct (Experiment 1) and mediated (Experiments 2 and 3) priming effects for reaction times and event-related potentials were observed within but not across equivalence relations. The findings support the argument that derived equivalence relations provides a useful preliminary model of semantic relations.
PMCID: PMC1389774  PMID: 16596973
derived equivalence relations; semantic priming; event-related potentials; humans; adults
Journal of Bacteriology  2004;186(8):2346-2354.
Down-regulation of expression of trmD, encoding the enzyme tRNA (guanosine-1)-methyltransferase, has shown that this gene is essential for growth of Streptococcus pneumoniae. The S. pneumoniae trmD gene has been isolated and expressed in Escherichia coli by using a His-tagged T7 expression vector. Recombinant protein has been purified, and its catalytic and physical properties have been characterized. The native enzyme displays a molecular mass of approximately 65,000 Da, suggesting that streptococcal TrmD is a dimer of two identical subunits. In fact, this characteristic can be extended to several other TrmD orthologs, including E. coli TrmD. Kinetic studies show that the streptococcal enzyme utilizes a sequential mechanism. Binding of tRNA by gel mobility shift assays gives a dissociation constant of 22 nM for one of its substrates, \documentclass[12pt]{minimal} \usepackage{amsmath} \usepackage{wasysym} \usepackage{amsfonts} \usepackage{amssymb} \usepackage{amsbsy} \usepackage{mathrsfs} \setlength{\oddsidemargin}{-69pt} \begin{document} \begin{equation*}{\mathit{tRNA}}_{{\mathit{CAG}}}^{{\mathit{Leu}}}\end{equation*}\end{document}. Other heterologous nonsubstrate tRNA species, like \documentclass[12pt]{minimal} \usepackage{amsmath} \usepackage{wasysym} \usepackage{amsfonts} \usepackage{amssymb} \usepackage{amsbsy} \usepackage{mathrsfs} \setlength{\oddsidemargin}{-69pt} \begin{document} \begin{equation*}{\mathit{tRNA}}_{{\mathit{GGT}}}^{{\mathit{Thr}}}\end{equation*}\end{document}, tRNAPhe, and \documentclass[12pt]{minimal} \usepackage{amsmath} \usepackage{wasysym} \usepackage{amsfonts} \usepackage{amssymb} \usepackage{amsbsy} \usepackage{mathrsfs} \setlength{\oddsidemargin}{-69pt} \begin{document} \begin{equation*}{\mathit{tRNA}}_{{\mathit{TGC}}}^{{\mathit{Ala}}}\end{equation*}\end{document}, bind the enzyme with similar affinities, suggesting that tRNA specificity is achieved via a postbinding event(s).
PMCID: PMC412112  PMID: 15060037
Gut  1993;34(12):1722-1725.
An immunohistochemical study has been carried out to compare and contrast the cellular distribution of two different sialosyl-Tn antigen binding monoclonal antibodies, MLS102 and B72.3, in the pancreas. MLS102 but not B72.3 monoclonal antibody binding increases with the content of the sialosyl-Tn epitopes. It was found that all 13 pancreatic cancer specimens bound both MLS102 and B72.3 monoclonal antibodies. Their cellular distribution in the cancer was virtually identical. Fifteen of 20 (75%) patients with chronic pancreatitis and five of 10 (50%) normal subjects were B72.3 positive, but MLS102 was completely negative in the latter group. Both monoclonal antibodies bound fetal pancreas diffusely. Thus, when pancreatic ductal cells have undergone malignant transformation, like the fetal pancreas, they express cell surface and secreted glycoconjugates with increased sialosyl-Tn epitopes suggesting enhanced 2-6 sialosyltransferase activity. This study shows that MLS102 is an extremely sensitive and specific tumour marker in the pancreas and that it is better than B72.3 in distinguishing pancreatic cancer from normal and chronic pancreatitis.
PMCID: PMC1374471  PMID: 8282261
Health Care Financing Review  1983;5(2):51-67.
This article provides data obtained through telephone interviews with 1,608 white, black, Mexican American, or Puerto Rican respondents. The study was designed to measure differences among ethnic groups in knowledge and attitudes toward long-term care services and the extent to which knowledge and attitudes affect service use.
Across all groups, there is less knowledge about long-term, community-based care than institutional services. The extent of knowledge about services is limited among all groups, but especially among Puerto Ricans. There are marked differences among groups in attitudes toward services. Minority groups are far more likely to perceive care of the elderly as a family responsibility and to stress the importance of ethnic factors in service delivery. Despite differences among groups, knowledge and attitudes are less directly related to use of services than is activity limitation. This may be because only a very small proportion of the respondents had any experience with service use.
PMCID: PMC4191332  PMID: 10310529
To use population-based, hospital discharge data to determine the extent to which demographic and geographic disparities exist in the use of PARC following stroke.
Cross-sectional analysis of two years (2005-2006) of population-based, hospital discharge data.
All short-term acute care hospitals in four demographically and geographically diverse states (AZ, FL, NJ, WI).
Individuals 45 years and older (mean age of 72.6 years) admitted to the hospital with a primary diagnosis of stroke, who survived their inpatient stay and who were not transferred to a hospice or other short-term, acute care facility (N=187,188). The sample was 52.4 percent female, 79.5 percent White, 11.4 percent Black, and 9.1 percent Hispanic.
Not applicable.
Main Outcome Measures
1) Discharge to an institution versus home. 2) For those discharged home, discharge home with or without home health (HH). 3) For those discharged to an institution, discharge to an inpatient rehabilitation facility (IRF) or skilled nursing facility (SNF). Multilevel logistic regression analyses were conducted to identify demographic and geographic disparities in PARC use, controlling for illness severity/comorbidities, hospital characteristics, and PARC supply.
Blacks, females, older individuals, and those with lower incomes were more likely to be discharged to an institution; Hispanic individuals and the uninsured were less likely. Racial minorities, females, older individuals, and those with lower incomes were more likely to receive HH; uninsured individuals and rural residents were less likely. Blacks, females, older individuals, the uninsured, and those with lower incomes were more likely to use SNF vs IRF care. PARC use varied significantly by state and by hospital.
Several demographic and geographic disparities in PARC use were identified.
PMCID: PMC4332528  PMID: 21807141
stroke; healthcare disparities; rehabilitation
Genes and immunity  2011;12(7):559-567.
The forkhead box transcription factor FoxP3 controls the development and function of CD4+CD25+ regulatory T (Treg) cell. FoxP3 modulates gene expression in Treg cells by multiple epigenetic mechanisms that are not clearly defined. We identified FoxP3 interacting proteins in human T cells by co-IP/MS. We discovered that FoxP3 interacted with linker histone H1.5 via the leucine zipper (LZ) domain. Two independent IPEX patient-derived single residue mutations in the LZ of FoxP3 both abrogated its interaction with H1.5. Functionally, FoxP3 and H1.5 cooperatively repressed IL-2 expression in human T cells; and silencing of H1.5 expression inhibited the ability of FoxP3 to suppress IL-2 expression. We show that FoxP3 specifically enhanced H1.5 association at the IL-2 promoter, but reduce its association at the CTLA4 promoter, correlated with higher or lower histone acetylation of the respective promoters. Finally, silencing of H1.5 expression in human Treg cells impaired the Treg function to suppress target T cells. We conclude that FoxP3 interacts with H1.5 to alter its binding to target genes to modulate their expression and to program Treg function.
PMCID: PMC4329728  PMID: 21654845
16.  CAH to CAH 
Applied Clinical Informatics  2014;5(1):92-117.
The US government allocated $30 billion to implement electronic health records (EHRs) in hospitals and provider practices through policy addressing Meaningful Use (MU). Most small, rural hospitals, particularly those designated as Critical Access Hospitals (CAHs), comprising nearly a quarter of US hospitals, had not implemented EHRs before. Little is known about implementation in this setting. Socio-technical factors differ between larger hospitals and CAHs, which continue to lag behind other hospitals in EHR adoption.
The main objective is to provide EHR implementation advice for CAHs from a spectrum of experts with an emphasis on recommendations from their peers at CAHs that have undertaken the process. The secondary objective is to begin to identify implementation process differences at CAHs v. larger hospitals.
We interviewed 41 experts, including 16 CAH staff members from EHR teams at 10 CAHs that recently implemented EHRs. We qualitatively analyzed the interviews to ascertain themes and implementation recommendations.
Nineteen themes emerged. Under each theme, comments by experts provide in-depth advice on all implementation stages including ongoing optimization and use. We present comments for three top themes as ranked by number of CAH peer experts commenting – EHR System Selection, EHR Team, and Preparatory Work – and for two others, Outside Partners/Resources and Clinical Decision Support (CDS)/Knowledge Management (KM). Comments for remaining themes are included in tables.
CAH experts rank the themes differently from all experts, a likely indication of the differences between hospitals. Comments for each theme indicate the specific difficulties CAHs encountered. CAH staffs have little or no EHR experience before implementation. A factor across themes is insufficient system and process knowledge, compounded by compressed implementation schedules. Increased, proactive self-education, via available outside partners and information resources, will mitigate difficulties and aid CAHs in meeting increased CDS requirements in MU Stages 2 and 3.
PMCID: PMC3974251  PMID: 24734127
Electronic health records; rural hospitals; critical access hospitals; qualitative research; medical informatics
JAMA ophthalmology  2014;132(7):820-822.
PMCID: PMC4324971  PMID: 25010167
Strabismus  2014;22(3):95-99.
We evaluated the use of botulinum toxin A in adults with convergence insufficiency in whom prior treatment had failed.
We studied 8 patients (median age 36 years, range 17 to 77 years) with reading symptoms due to convergence insufficiency defined as an exodeviation greater at near, not exceeding 10 PD in the distance measured by prism and alternate cover test, and either convergence near point >6 cm or reduced fusional amplitudes. All patients were still symptomatic after prior treatment by convergence exercises (n = 8), base-in prism glasses (n = 5) or strabismus surgery (n = 2). Five patients received injection of 5 IU botulinum toxin in 0.1 ml saline to one lateral rectus muscle, two received 2.5 IU, and one received 2.5 IU to both lateral rectus muscles.
At 1 month post injection, all patients had an initial reduction of exodeviation from baseline (median 9 PD, p = 0.008) at near, although 2 patients had a temporary intermittent esotropia in the distance with diplopia associated with difficulty driving. At 6 months, when the pharmacological effect of botulinum toxin had completely worn off, patients still maintained a small reduction of exodeviation (median 4 PD, p = 0.3) at near. Reading symptoms improved in 7 of 8 patients at 1-month post injection, and in all patients at 6 months. Two patients had health-related quality of life assessed with the Adult Strabismus 20 Questionnaire, showing improved Reading Function scores at 6 months. Interestingly, 3 patients reported improved reading despite returning to the baseline angle at 6 months, and 2 of 4 with 12-month follow-up still reported improvement.
In adult convergence insufficiency, botulinum toxin injection to a lateral rectus muscle improves reading symptoms beyond the duration of the pure pharmacological effect. Botulinum toxin injection may be useful in management of adult convergence insufficiency, although repeat injections may be needed.
PMCID: PMC4324975  PMID: 24786379
Botox; Botulinum toxin; convergence insufficiency; reading function; strabismus
A simple risk score to predict long-term mortality after percutaneous coronary intervention (PCI) using pre-procedural risk factors is currently not available. In this study, we created one by simplifying the results of a Cox proportional hazards model.
Methods and Results
A total of 11,897 patients who underwent PCI from October through December 2003 in New York State were randomly divided into derivation and validation samples. Patients’ vital statuses were tracked using the National Death Index through the end of 2008. A Cox proportional hazards model was fit to predict death after PCI using the derivation sample, and a simplified risk score was created. The Cox model identified 12 separate risk factors for mortality including older age, extreme body mass indexes, multivessel disease, a lower ejection fraction, unstable hemodynamic state or shock, a number of comorbidities (cerebrovascular disease, peripheral vascular disease, congestive heart failure, chronic obstructive pulmonary disease, diabetes, and renal failure), and a history of coronary artery bypass graft surgery. The C statistics of this model when applied to the validation sample were 0.787, 0.785, and 0.773 for risks of death within 1, 3, and 5 years after PCI, respectively. In addition, the point-based risk score demonstrated good agreement between patients’ observed and predicted risks of death.
A simple risk score created from a more complicated Cox proportional hazards model can be used to accurately predict a patient's risk of long-term mortality after PCI.
PMCID: PMC4121885  PMID: 24425588
PCI; follow-up study; mortality; risk score
Virology  2013;0:2-12.
Lymphoproliferative disease virus (LPDV) is an exogenous oncogenic retrovirus that induces lymphoid tumors in some galliform species of birds. Historically, outbreaks of LPDV have been reported from Europe and Israel. Although the virus has previously never been detected in North America, herein we describe the widespread distribution, genetic diversity, pathogenesis, and evolution of LPDV in the United States. Characterization of the provirus genome of the index LPDV case from North America demonstrated an 88% nucleotide identity to the Israeli prototype strain. Although phylogenetic analysis indicated that the majority of viruses fell into a single North American lineage, a small subset of viruses from South Carolina were most closely related to the Israeli prototype. These results suggest that LPDV was transferred between continents to initiate outbreaks of disease. However, the direction (New World to Old World or vice versa), mechanism, and time frame of the transcontinental spread currently remain unknown.
PMCID: PMC3925403  PMID: 24503062
Lymphoproliferative disease virus (LPDV); alpharetrovirus; avian tumor viruses; exogenous retrovirus; oncogenesis; Order Galliformes
In decisions to adopt and implement new practices or innovations in child welfare, costs are often a bottom-line consideration. The cost calculator, a method developed in England that can be used to calculate unit costs of core case work activities and associated administrative costs, is described as a potentially helpful tool for assisting child welfare administrators to evaluate the costs of current practices relative to their outcomes and could impact decisions about whether to implement new practices. The process by which the cost calculator is being adapted for use in US child welfare systems in two states is described and an illustration of using the method to compare two intervention approaches is provided.
PMCID: PMC4312008  PMID: 20976620
Cost calculator in child welfare; Unit costs of children’s services; Placement costs
PLoS Neglected Tropical Diseases  2015;9(1):e0003442.
Dengue virus (DENV) transmission is ubiquitous throughout the tropics. More than 70% of the current global dengue disease burden is borne by people who live in the Asia-Pacific region. We sequenced the E gene of DENV isolated from travellers entering Western Australia between 2010–2012, most of whom visited Indonesia, and identified a diverse array of DENV1-4, including multiple co-circulating viral lineages. Most viruses were closely related to lineages known to have circulated in Indonesia for some time, indicating that this geographic region serves as a major hub for dengue genetic diversity. Most notably, we identified a new lineage of DENV-2 (Cosmopolitan genotype) that emerged in Bali in 2011–2012. The spread of this lineage should clearly be monitored. Surveillance of symptomatic returned travellers provides important and timely information on circulating DENV serotypes and genotypes, and can reveal the herald wave of dengue and other emerging infectious diseases.
Author Summary
Dengue is currently the most rapidly spreading mosquito-borne viral disease of humans, and is endemic in most tropical and sub-tropical countries. An estimated 390 million infections occur annually, and over 70% of the current global dengue disease burden is borne by people who live in Southeast Asia and the Western Pacific region. DENV serotype and genotype data is lacking in many parts of this region, limiting our attempts to understand the observed patterns of hyperendemicity and disease severity. Many countries in the Southeast Asia and Western Pacific region are popular tourist destinations, and dengue has been identified as a cause of travel-related illness in people returning from endemic countries. We sequenced the E gene of DENV isolated from travellers returning to Western Australia from 7 countries throughout Asia between 2010 and 2012. The majority of DENV originated in Indonesia, predominantly Bali, a popular travel destination for Australians. We identified hyperendemic transmission of all four DENV serotypes in Bali in 2010; circulating DENV included dominant local strains which had circulated for several years in Indonesia and Singapore, as well as strains more recently introduced into Bali from other countries in the region. Finally, we show the emergence of a new lineage of DENV2 (Cosmopolitan genotype) in 2011–2012, which should be monitored. Travellers may act as sentinels and provide important information on DENV genotypes and linages circulating in countries where locally generated detailed genetic data may not be available.
PMCID: PMC4311992  PMID: 25635775
In order to determine if electronic circular dichroism (ECD) is a good tool for the qualitative evaluation of absolute configuration and enantiopurity in the absence of chiral high performance liquid chromatography (HPLC), ECD studies were performed on several prescriptions and over-the-counter drugs. Cotton effects (CE) were observed for both S and R isomers between 200 and 300 nm. For the drugs examined in this study, the S isomers showed a negative CE, while the R isomers displayed a positive CE. The ECD spectra of both enantiomers were nearly mirror images, with the amplitude proportional to the enantiopurity. Plotting the differential extinction coefficient (Δε) versus enantiopurity at the wavelength of maximum amplitude yielded linear standard curves with coefficients of determination (R2) greater than 97% for both isomers in all cases. As expected, Equate, Advil, and Motrin, each containing a racemic mixture of ibuprofen, yielded no chiroptical signal. ECD spectra of Suphedrine and Sudafed revealed that each of them is rich in 1S,2S-pseudoephedrine, while the analysis of Equate vapor inhaler is rich in R-methamphetamine.
PMCID: PMC4326340
Nature Communications  2015;6:6013.
Solution-processed organic photovoltaic cells (OPVs) hold great promise to enable roll-to-roll printing of environmentally friendly, mechanically flexible and cost-effective photovoltaic devices. Nevertheless, many high-performing systems show best power conversion efficiencies (PCEs) with a thin active layer (thickness is ~100 nm) that is difficult to translate to roll-to-roll processing with high reproducibility. Here we report a new molecular donor, benzodithiophene terthiophene rhodanine (BTR), which exhibits good processability, nematic liquid crystalline behaviour and excellent optoelectronic properties. A maximum PCE of 9.3% is achieved under AM 1.5G solar irradiation, with fill factor reaching 77%, rarely achieved in solution-processed OPVs. Particularly promising is the fact that BTR-based devices with active layer thicknesses up to 400 nm can still afford high fill factor of ~70% and high PCE of ~8%. Together, the results suggest, with better device architectures for longer device lifetime, BTR is an ideal candidate for mass production of OPVs.
There is a trade-off between increasing thickness of active layers in organic photovoltaic cells to be compatible with modern printing techniques and decreasing it to improve the device performance. Sun et al. report a nematic liquid crystalline molecular electron donor material used in thick layers.
PMCID: PMC4309440  PMID: 25586307

Results 1-25 (3420)