Protection of rhesus monkeys from fatal Lassa fever by vaccination with a recombinant vaccinia virus containing the Lassa virus glycoprotein gene.

Lassa fever is an acute febrile disease of West Africa, where there are as many as 300,000 infections a year and an estimated 3000 deaths. As control of the rodent host is impracticable at present, the best immediate prospect is vaccination. We tested as potential vaccines in rhesus monkeys a closely related virus, Mopeia virus (two monkeys), and a recombinant vaccinia virus containing the Lassa virus glycoprotein gene, V-LSGPC (four monkeys). Two monkeys vaccinated with the New York Board of Health strain of vaccinia virus as controls died after challenge with Lassa virus. The two monkeys vaccinated with Mopeia virus developed antibodies measurable by radioimmunoprecipitation prior to challenge, and they survived challenge by Lassa virus with minimal physical or physiologic disturbances. However, both showed a transient, low-titer Lassa viremia. Two of the four animals vaccinated with V-LSGPC had antibodies to both Lassa glycoproteins, as determined by radioimmunoprecipitation. All four animals survived a challenge of Lassa virus but experienced a transient febrile illness and moderate physiologic changes following challenge. Virus was recoverable from each of these animals, but at low titer and only during a brief period, as observed for the Mopeia-protected animals. We conclude that V-LSGPC can protect rhesus monkeys against death from Lassa fever.     

Pattern classification of response inhibition in ADHD: Toward the development of neurobiological markers for ADHD

The diagnosis of Attention Deficit Hyperactivity Disorder (ADHD) is based on subjective measures despite evidence for multisystemic structural and functional deficits. ADHD patients have consistent neurofunctional deficits in motor response inhibition. The aim of this study was to apply pattern classification to task‐based functional magnetic resonance imaging (fMRI) of inhibition, to accurately predict the diagnostic status of ADHD. Thirty adolescent ADHD and thirty age‐matched healthy boys underwent fMRI while performing a Stop task. fMRI data were analyzed with Gaussian process classifiers (GPC), a machine learning approach, to predict individual ADHD diagnosis based on task‐based activation patterns. Traditional univariate case‐control analyses were also performed to replicate previous findings in a relatively large dataset. The pattern of brain activation correctly classified up to 90% of patients and 63% of controls, achieving an overall classification accuracy of 77%. The regions of the discriminative network most predictive of controls included later developing lateral prefrontal, striatal, and temporo‐parietal areas that mediate inhibition, while regions most predictive of ADHD were in earlier developing ventromedial fronto‐limbic regions, which furthermore correlated with symptom severity. Univariate analysis showed reduced activation in ADHD in bilateral ventrolateral prefrontal, striatal, and temporo‐parietal regions that overlapped with areas predictive of controls, suggesting the latter are dysfunctional areas in ADHD. We show that significant individual classification of ADHD patients of 77% can be achieved using whole brain pattern analysis of task‐based fMRI inhibition data, suggesting that multivariate pattern recognition analyses of inhibition networks can provide objective diagnostic neuroimaging biomarkers of ADHD. Hum Brain Mapp 35:3083–3094, 2014. © 2013 Wiley Periodicals, Inc.     

Pathogenic potential of filoviruses: role of geographic origin of primate host and virus strain.

African filoviruses have caused outbreaks of fulminating hemorrhagic fever among humans. In 1989, related filoviruses were isolated from cynomolgus monkeys imported into the United States from the Philippines. The pathogenic potential of these new filoviruses was compared in 16 Asian monkeys (Macaca fascicularis-cynomolgus) and 16 African monkeys (Cercopithecus aethiops-African green) using African filoviruses from Zaire (Ebola virus) and Sudan or Asian filoviruses (Reston and Pennsylvania). African filovirus infections resulted in earlier death (P = .005), had a shorter duration of disease and median incubation period (3-4 vs. 7 days), and had earlier peak viremia (5-7 vs. 7-9 days). African green monkeys showed significantly higher survival than cynomolgus monkeys (P less than .01), and some were asymptomatic as have been humans accidentally infected with Asian filovirus. Rechallenge experiments showed that protection in survivors of filovirus infections against fatal challenge with Ebola (Zaire) virus is unpredictable. The minimal clinical disease observed in humans infected with the Reston strain is consistent with host- and virus-dependent pathogenicity.     

Monoclonal antibodies to three strains of hantaviruses: Hantaan,R22, and Puumala

Summary Thirty hybrid cell lines that produce monoclonal antibodies to three strains of hantaviruses have been generated and characterized. One clone specific to Hantaan 76–118 strain, four clones specific to Rattus strains and one clone specific to Puumala virus have been identified. Most of the monoclones produced antibodies specific to nucleoproteins. Only two monoclones were found to produce glycoprotein specific, neutralizing antibodies. The immunofluorescent (IFA) staining patterns of the monoclonal antibodies show consistent correlation with viral protein specificities as described for other hemorrhagic fever viruses. Cross-reactivity studies with hantaviruses tested demonstrate conserved antigenic sites on nucleoproteins among these hantaviruses tested. Puumala specific monoclones, produced for the first time, reveal both conserved and strain specific sites on the viral nucleoproteins of the Scandinavian virus.     

Registration of dynamic dopamine D2 receptor images using principal component analysis

This paper describes a novel technique for registering a dynamic sequence of single-photon emission tomography (SPET) dopamine D₂ receptor images, using principal component analysis (PCA). Conventional methods for registering images, such as count difference and correlation coefficient algorithms, fail to take into account the dynamic nature of the data, resulting in large systematic errors when registering time-varying images. However, by using principal component analysis to extract the temporal structure of the image sequence, misregistration can be quantified by examining the distribution of eigenvalues. The registration procedures were tested using a computer-generated dynamic phantom derived from a high-resolution magnetic resonance image of a realistic brain phantom. Each method was also applied to clinical SPET images of dopamine D₂ receptors, using the ligands iodine-123 iodobenzamide and iodine-123 epidepride, to investigate the influence of misregistration on kinetic modelling parameters and the binding potential. The PCA technique gave highly significant (P<0.001) improvements in image registration, leading to alignment errors in x and y of about 25% of the alternative methods, with reductions in autocorrelations over time. It could also be applied to align image sequences which the other methods failed completely to register, particularly ¹²³I-epidepride scans. The PCA method produced data of much greater quality for subsequent kinetic modelling, with an improvement of nearly 50% in the χ ² of the fit to the compartmental model, and provided superior quality registration of particularly difficult dynamic sequences. Received 1 August and in revised form 21 August 1997     

Identification and quantification of water-soluble hydrocarbons generated by two-cycle outboard motors

A 7.0 horsepower (HP) and a 10.0 HP outboard motor were operated at 3,500±200 rpm and 1,700±200 rpm, respectively for 30 min in a 160 L tank of tapwater. Exhaust hydrocarbons were concentrated by passage through a C₁₈ reverse phase extraction column, and eluted with either ethylacetate or acetonitrile. Gas-liquid and/or high pressure liquid chromatographic procedures were used for identification and quantification of eight hydrocarbons. Identities were confirmed for seven of the compounds by GLC/mass spectrometry. Four additional hydrocarbons were tentatively identified with these procedures. Aromatic compounds composed the majority of the hydrocarbons detected; a few aliphatics were present in trace amounts.     

Use of a portable thermal imaging unit as a rapid, quantitative method of evaluating inflammation and experimental arthritis

INTRODUCTION: Thermal imaging has been utilized, both preclinically and clinically, as a tool for assessing inflammation and arthritis. However, previous studies have employed large, relatively immobile devises to obtain the thermal signature of the tissue of interest. The present study describes the characterization of a hand-held thermal imaging device in a preclinical model of general inflammation and a model of rheumatoid arthritis (RA). METHODS: A hand-held ThermoView Ti30 portable thermal imager was utilized to detect the temporal changes in thermal signatures in rat model of carrageenan-induced paw edema (CFE) and a model of collagen-induced arthritis (CIA). In both in vivo models, the kinetics of the thermal changes were correlated to footpad swelling. In addition, the CFE model was utilized to examine the ability of this technology to delineate pharmacodynamic changes in thermal signature in response to the non-steroidal anti-inflammatory drug indomethacin (10 mg/kg; p.o.). RESULTS: Thermal analysis of rat paws in the CFE model demonstrated a significant increase in the mean temperature difference between the inflamed and contralateral control paw by two hours post-carrageenan (8.3 +/-0.5 degrees F). Indomethacin significantly decreased the mean temperature difference in treated animals as compared to vehicle. In the rat CIA model, increases in footpad temperature, as determined by thermal imaging, were significantly elevated by Day 11 and remained elevated throughout the duration of the 28 day protocol. Thermal changes were also found to precede increases in footpad edema (swelling). DISCUSSION: The results of this study demonstrate that the hand-held thermal imaging technology represents a rapid, highly-reproducible method by which to quantitate the degree of inflammation in rat models of general inflammation and rheumatoid arthritis. The ability to detect pharmacodynamic responses in paw temperature suggests that this technology may be a useful tool for the development of pharmacologic interventions for the treatment inflammation-related pathologies.     

Parental ADHD and Depression: Time-Varying Prediction of Offspring Externalizing Psychopathology

Parental attention deficit/hyperactivity disorder (ADHD) and depression are risk factors for negative child outcomes, but given their frequent co-occurrence and variability over time, developmentally sensitive studies are needed. To characterize change in parental ADHD and depression as predictors of change in child ADHD and oppositional defiant disorder (ODD), 230 five- to ten-year-old children with (n = 110) and without (n = 120) ADHD were followed prospectively for 2 years with 90% retention. At baseline and again 2 years later (i.e., Wave 2), parents self-reported their ADHD and depression; parents and teachers also separately rated child ADHD and ODD, as well as broader attention and externalizing problems. Controlling for child sex, race-ethnicity, age, and parental depression, generalized estimating equations revealed that 2-year decreases in parental ADHD significantly predicted reduced child ADHD symptoms, but only among non-ADHD youth. Alternatively, increasing parental depression positively predicted change in teacher-rated ODD symptoms. These findings provide quasi-experimental evidence that parental ADHD and depression may be time-varying risk factors with respect to key dimensions of child externalizing behavior problems. We consider the potential dynamic and reciprocal interrelations among parental ADHD and depression with developmental change in offspring ADHD and ODD. We also discuss implications of parent psychopathology in the development of interventions to reduce the burden of youth ADHD and associated externalizing behavior.     

Assessing psychometric properties of scales: a case study

AIM: This paper is a report of a study to examine the construct validity of The Nursing Students' Attitudes and Awareness of Research and Development within Nursing Scale. BACKGROUND: The validity of instruments is critical in ensuring that data collected are sound and that the data measures what it purports to measure. When a new instrument is used in a different population or when it has been modified, it is useful to re-examine the construct validity of the instrument. METHOD: A survey design was used in September 2004 with a sample of 615 undergraduate nursing students to test the factor structure of The Nursing Students' Attitudes and Awareness of Research and Development within Nursing Scale and to estimate its similarity to the factor structure reported for the original scale developed and tested in a group of Registered Nurses. Results: Using Maximum Likelihood Factor Analysis and then Principal Axis Factoring, we were unable to obtain a similar factor structure to that originally identified for the scale. Our data resulted in a two-factor structure. One factor consisted of 16 items that reflected a positive attitude to nursing research and the other consisted of 14 items that reflected a negative attitude to nursing research. CONCLUSION: The substantially different factor structure identified suggests that this scale requires further refinement and testing. This case study highlights the importance of a systematic and comprehensive approach to determining construct validity of scales, thus enabling researchers to determine their suitability as data collection instruments.