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Find video protocols related to scientific articles indexed in Pubmed.
Peer Leaders and Substance Use Among High-Risk Adolescents.
Subst Use Misuse
PUBLISHED: 11-20-2014
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Objective: To examine the association between individual drug use and peer leaders use. Method: Analysis of drug use behaviors of 525 students randomized into three arms-control, standard, and networked where peers serve as group leaders. Results: Among the combined male and female group, there was no association between peer leader and individual use. Among males, peer leader use at baseline was positively associated with individual alcohol use at post-test. Among females, peer leader use at post-test was negatively associated with marijuana and cigarette use. Conclusion: Having peer leaders in the network condition decreased the odds of marijuana and cigarette use among females. The opposite effect was found in males.
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PEGylation and its impact on the design of new protein-based medicines.
Future Med Chem
PUBLISHED: 11-20-2014
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PEGylation is the covalent conjugation of PEG to therapeutic molecules. Protein PEGylation is a clinically proven approach for extending the circulation half-life and reducing the immunogenicity of protein therapeutics. Most clinically used PEGylated proteins are heterogeneous mixtures of PEG positional isomers conjugated to different residues on the protein main chain. Current research is focused to reduce product heterogeneity and to preserve bioactivity. Recent advances and possible future directions in PEGylation are described in this review. So far protein PEGylation has yielded more than 10 marketed products and in view of the lack of equally successful alternatives to extend the circulation half-life of proteins, PEGylation will still play a major role in drug delivery for many years to come.
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Detection and drivers of exposure and effects of pharmaceuticals in higher vertebrates.
Philos. Trans. R. Soc. Lond., B, Biol. Sci.
PUBLISHED: 11-19-2014
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Pharmaceuticals are highly bioactive compounds now known to be widespread environmental contaminants. However, research regarding exposure and possible effects in non-target higher vertebrate wildlife remains scarce. The fate and behaviour of most pharmaceuticals entering our environment via numerous pathways remain poorly characterized, and hence our conception and understanding of the risks posed to wild animals is equally constrained. The recent decimation of Asian vulture populations owing to a pharmaceutical (diclofenac) offers a notable example, because the exposure route (livestock carcasses) and the acute toxicity observed were completely unexpected. This case not only highlights the need for further research, but also the wider requirement for more considered and comprehensive 'ecopharmacovigilance'. We discuss known and potential high risk sources and pathways in terrestrial and freshwater ecosystems where pharmaceutical exposure in higher vertebrate wildlife, principally birds and mammals, may occur. We examine whether approaches taken within existing surveillance schemes (that commonly target established classes of persistent or bioaccumulative contaminants) and the risk assessment approaches currently used for pesticides are relevant to pharmaceuticals, and we highlight where new approaches may be required to assess pharmaceutical-related risk.
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Polymers Zippered-Up by Electric Charge Reveal Themselves.
ACS Nano
PUBLISHED: 11-18-2014
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In the current issue of ACS Nano, Löbling, Haataja et al. craft polymeric nanoparticles with a hierarchy of nontrivial surface structures by combining conventional interpolyelectrolyte complexation with steric control from an uncharged copolymer block. Remarkable cylindrical and lamellar nanodomains are produced on the polyionic coronae of spherical micelles. Here, we discuss generalizing this elegant self-assembly strategy and provide speculative perspectives for its future potential for new nanomaterials.
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Tunable wideband microwave photonic phase shifter using on-chip stimulated Brillouin scattering.
Opt Express
PUBLISHED: 11-18-2014
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We present the first microwave photonic phase shifter using stimulated Brillouin scattering (SBS) on-chip. The unique ability of SBS to generate both narrowband gain and loss resonances allows us to achieve low ±1.5 dB amplitude fluctuations, which is a record for integrated devices, along with 240° continuously tunable phase shift. Contrary to previous SBS-based approaches, the phase shift tuning mechanism relies on tuning the power, not the frequency, of two SBS pumps, making it more suited to on-chip implementations. We finally demonstrate that SBS pump depletion leads to amplitude response fluctuations, as well as increasing the insertion loss of the phase shifter. Advantageously, shorter integrated platforms possess higher pump depletion thresholds compared to long fibers, thus offering greater potential for reducing the insertion loss.
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Inhibition of PI3K? signaling with AZD8186 inhibits growth of PTEN deficient breast and prostate tumour alone and in combination with docetaxel.
Mol. Cancer Ther.
PUBLISHED: 11-14-2014
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Loss of PTEN protein results in upregulation of the PI3K/AKT pathway, which appears dependent on the PI3K? isoform. Inhibitors of PI3K? have potential to reduce growth of tumours in which loss of PTEN drives tumour progression. We have developed a small molecule inhibitor of PI3K? and PI3K? (AZD8186) and assessed its anti-tumour activity across a panel of cell lines. We have then explored the anti-tumour effects as single agent and in combination with docetaxel in triple negative breast (TNBC) and prostate cancer models. In vitro AZD8186 inhibited growth of a range of cell lines. Sensitivity was associated with inhibition of the AKT pathway. Cells sensitive to AZD8186 (GI50?1?M) are enriched for, but not exclusively associated with, PTEN deficiency. In vivo AZD8186 inhibits PI3K pathway biomarkers in prostate and TNBC tumours. Scheduling treatment with AZD8186 shows anti-tumour activity required only intermittent exposure, and that increased tumour control is achieved when AZD8186 is used in combination with docetaxel. AZD8186 is a potent inhibitor of PI3K? with activity against PI3K? signalling, and has potential to reduce growth of tumours dependent on dysregulated PTEN for growth. Moreover AZ8186 can be combined with docetaxel, a chemotherapy commonly used to treat advance TBNC and prostate tumours. The ability to schedule AZD8186 and maintain efficacy offers opportunity to combine AZD8186 more effectively with other drugs.
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Post-traumatic growth, stressful life events, and relationships with substance use behaviors among alternative high school students: A prospective study.
Psychol Health
PUBLISHED: 10-28-2014
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A highly stressful life event (SLE) can elicit positive psychosocial growth, referred to as post-traumatic growth (PTG) among youth. We examined PTG and the number of SLEs for their influence on substance use behaviours among a sample of older, diverse alternative high school students participating in a drug prevention programme (n = 564; mean age = 16.8; 49% female; 65% Hispanic). Surveys assessed PTG, SLEs and substance use behaviours at the two-year follow-up. Multilevel regression models were run to examine the effect of PTG and the number of SLEs on frequency of substance use at the two-year follow-up, controlling for baseline substance use, sociodemographic variables, peer substance use, attrition propensity and treatment group. Greater PTG scores were associated with lower frequencies of alcohol use, getting drunk on alcohol, binge drinking, marijuana use and less substance abuse at the two-year follow-up, but not associated with cigarette or hard drug use. Also, PTG did not moderate the relationship between cumulative number of SLEs and substance use behaviours, rather PTG appears to be protective against negative effects of a single, life-altering SLE. Fostering PTG from a particularly poignant SLE may be useful for prevention programmes targeting alcohol, marijuana and substance abuse behaviours among high-risk youth.
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Does neuroanatomy account for superior temporal dysfunction in early psychosis? A multimodal MRI investigation.
J Psychiatry Neurosci
PUBLISHED: 10-23-2014
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Neuroimaging studies of ultra-high risk (UHR) and first-episode psychosis (FEP) have revealed widespread alterations in brain structure and function. Recent evidence suggests there is an intrinsic relationship between these 2 types of alterations; however, there is very little research linking these 2 modalities in the early stages of psychosis.
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Sense of Coherence and Tobacco Use Myths Among Adolescents as Predictors of At-Risk Youth Cigarette Use.
Subst Use Misuse
PUBLISHED: 09-30-2014
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We examined the association between a general construct of wellness beliefs, sense of coherence, and a specific measure of tobacco-related beliefs, tobacco use myths, as predictors of two smoking-related outcome measures-next year smoking expectation and last 30-day smoking. Self-report questionnaires were administered to 710 adolescents attending California continuation high schools at baseline and at 1-year follow-up between 2006 and 2008. Cross-sectionally, predictor and outcome measures were correlated. However, in longitudinal analyses, only tobacco use myths predicted change in outcome measures. We speculate that future smoking interventions among adolescents would achieve relatively efficacious outcomes by targeting specific health beliefs instead of global health beliefs. The study's limitations are noted.
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Voids and yolk-shells from crystals that coat particles.
J. Am. Chem. Soc.
PUBLISHED: 09-22-2014
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We investigate curvature-driven core-shell morphology that emerges when polycrystalline shells of ZIF-8 (zeolitic imidazolate framework coordination polymer) grow on colloid-sized particles. In early growth stages, the shell is continuous, but it transforms to yolk-shell, with neither sacrificial template nor core etching, because of geometrical frustration. A design rule is developed regarding how local surface curvature matters. Comparing shells grown on cubic, rod-like, and peanut-shaped hematite core particles, we validate the argument.
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Changing Attitudes Toward Smoking and Smoking Susceptibility Through Peer Crowd Targeting: More Evidence From a Controlled Study.
Health Commun
PUBLISHED: 09-11-2014
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Peer crowd identification consistently predicts an adolescent's smoking behavior. As such, several interventions have targeted adolescents and young adults based on their identification with a specific crowd (e.g., Hipsters). This study uses a controlled experimental design to isolate and test the effect of peer crowd targeting in an antismoking ad on antismoking attitudes and smoking susceptibility. Two hundred and thirty-nine adolescents, age 13-15 years, completed a baseline survey and then viewed an antismoking ad targeting one of eight crowds; 1 week later they completed a posttest. Participants were assessed on antismoking attitudes and smoking susceptibility. Adolescents who strongly identified with the crowd targeted by the ad reported stronger antismoking attitudes and lower levels of smoking susceptibility. Those who disidentified with the crowd targeted in the ad exhibited not statistically significant increases in smoking susceptibility and weaker antismoking attitudes at posttest. These findings indicate that targeting youths based on their peer crowd is a useful strategy for antismoking interventions. Additional research should further examine whether youths who disidentify with the targeted crowd in an ad exhibit reactance against the message.
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The impact of sleep and hypoxia on the brain: potential mechanisms for the effects of obstructive sleep apnea.
Curr Opin Pulm Med
PUBLISHED: 09-05-2014
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Obstructive sleep apnea (OSA) is a chronic, highly prevalent, multisystem disease, which is still largely underdiagnosed. Its most prominent risk factors, obesity and older age, are on the rise, and its prevalence is expected to grow further. The last few years have seen an exponential increase in studies to determine the impact of OSA on the central nervous system. OSA-induced brain injury is now a recognized clinical entity, although its possible dual relationship with several other neuropsychiatric and neurodegenerative disorders is debated. The putative neuromechanisms behind some of the effects of OSA on the central nervous system are discussed in this review, focusing on the nocturnal intermittent hypoxia and sleep fragmentation.
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The genomic substrate for adaptive radiation in African cichlid fish.
Nature
PUBLISHED: 09-03-2014
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Cichlid fishes are famous for large, diverse and replicated adaptive radiations in the Great Lakes of East Africa. To understand the molecular mechanisms underlying cichlid phenotypic diversity, we sequenced the genomes and transcriptomes of five lineages of African cichlids: the Nile tilapia (Oreochromis niloticus), an ancestral lineage with low diversity; and four members of the East African lineage: Neolamprologus brichardi/pulcher (older radiation, Lake Tanganyika), Metriaclima zebra (recent radiation, Lake Malawi), Pundamilia nyererei (very recent radiation, Lake Victoria), and Astatotilapia burtoni (riverine species around Lake Tanganyika). We found an excess of gene duplications in the East African lineage compared to tilapia and other teleosts, an abundance of non-coding element divergence, accelerated coding sequence evolution, expression divergence associated with transposable element insertions, and regulation by novel microRNAs. In addition, we analysed sequence data from sixty individuals representing six closely related species from Lake Victoria, and show genome-wide diversifying selection on coding and regulatory variants, some of which were recruited from ancient polymorphisms. We conclude that a number of molecular mechanisms shaped East African cichlid genomes, and that amassing of standing variation during periods of relaxed purifying selection may have been important in facilitating subsequent evolutionary diversification.
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Rabbit genome analysis reveals a polygenic basis for phenotypic change during domestication.
Science
PUBLISHED: 08-30-2014
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The genetic changes underlying the initial steps of animal domestication are still poorly understood. We generated a high-quality reference genome for the rabbit and compared it to resequencing data from populations of wild and domestic rabbits. We identified more than 100 selective sweeps specific to domestic rabbits but only a relatively small number of fixed (or nearly fixed) single-nucleotide polymorphisms (SNPs) for derived alleles. SNPs with marked allele frequency differences between wild and domestic rabbits were enriched for conserved noncoding sites. Enrichment analyses suggest that genes affecting brain and neuronal development have often been targeted during domestication. We propose that because of a truly complex genetic background, tame behavior in rabbits and other domestic animals evolved by shifts in allele frequencies at many loci, rather than by critical changes at only a few domestication loci.
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Super-resolution study of polymer mobility fluctuations near c*.
ACS Nano
PUBLISHED: 08-22-2014
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Nanoscale dynamic heterogeneities in synthetic polymer solutions are detected using super-resolution optical microscopy. To this end, we map concentration fluctuations in polystyrene-toluene solutions with spatial resolution below the diffraction limit, focusing on critical fluctuations near the polymer overlap concentration, c*. Two-photon super-resolution microscopy was adapted to be applicable in an organic solvent, and a home-built STED-FCS system with stimulated emission depletion (STED) was used to perform fluorescence correlation spectroscopy (FCS). The polystyrene serving as the tracer probe (670 kg mol(-1), radius of gyration RG ? 35 nm, end-labeled with a bodipy derivative chromophore) was dissolved in toluene at room temperature (good solvent) and mixed with matrix polystyrene (3,840 kg mol(-1), RG ? 97 nm, Mw/Mn = 1.04) whose concentration was varied from dilute to more than 10c*. Whereas for dilute solutions the intensity-intensity correlation function follows a single diffusion process, it splits starting at c* to imply an additional relaxation process provided that the experimental focal area does not greatly exceed the polymer blob size. We identify the slower mode as self-diffusion and the increasingly rapid mode as correlated segment fluctuations that reflect the cooperative diffusion coefficient, Dcoop. These real-space measurements find quantitative agreement between correlation lengths inferred from dynamic measurements and those from determining the limit below which diffusion coefficients are independent of spot size. This study is considered to illustrate the potential of importing into polymer science the techniques of super-resolution imaging.
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Predicting progression of Alzheimer's disease using ordinal regression.
PLoS ONE
PUBLISHED: 08-20-2014
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We propose a novel approach to predicting disease progression in Alzheimer's disease (AD)--multivariate ordinal regression--which inherently models the ordered nature of brain atrophy spanning normal aging (CTL) to mild cognitive impairment (MCI) to AD. Ordinal regression provides probabilistic class predictions as well as a continuous index of disease progression--the ORCHID (Ordinal Regression Characteristic Index of Dementia) score. We applied ordinal regression to 1023 baseline structural MRI scans from two studies: the US-based Alzheimer's Disease Neuroimaging Initiative (ADNI) and the European based AddNeuroMed program. Here, the acquired AddNeuroMed dataset was used as a completely independent test set for the ordinal regression model trained on the ADNI cohort providing an optimal assessment of model generalizability. Distinguishing CTL-like (CTL and stable MCI) from AD-like (MCI converters and AD) resulted in balanced accuracies of 82% (cross-validation) for ADNI and 79% (independent test set) for AddNeuroMed. For prediction of conversion from MCI to AD, balanced accuracies of 70% (AUC of 0.75) and 75% (AUC of 0.81) were achieved. The ORCHID score was computed for all subjects. We showed that this measure significantly correlated with MMSE at 12 months (? =? -0.64, ADNI and ? = ?-0.59, AddNeuroMed). Additionally, the ORCHID score can help fractionate subjects with unstable diagnoses (e.g. reverters and healthy controls who later progressed to MCI), moderately late converters (12-24 months) and late converters (24-36 months). A comparison with results in the literature and direct comparison with a binary classifier suggests that the performance of this framework is highly competitive.
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3D GRASE pulsed arterial spin labeling at multiple inflow times in patients with long arterial transit times: comparison with dynamic susceptibility-weighted contrast-enhanced MRI at 3 Tesla.
J. Cereb. Blood Flow Metab.
PUBLISHED: 06-26-2014
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Pulsed arterial spin labeling (PASL) at multiple inflow times (multi-TIs) is advantageous for the measurement of brain perfusion in patients with long arterial transit times (ATTs) as in steno-occlusive disease, because bolus-arrival-time can be measured and blood flow measurements can be corrected accordingly. Owing to its increased signal-to-noise ratio, a combination with a three-dimensional gradient and spin echo (GRASE) readout allows acquiring a sufficient number of multi-TIs within a clinically feasible acquisition time of 5?minutes. We compared this technique with the clinical standard dynamic susceptibility-weighted contrast-enhanced imaging-magnetic resonance imaging in patients with unilateral stenosis >70% of the internal carotid or middle cerebral artery (MCA) at 3 Tesla. We performed qualitative (assessment by three expert raters) and quantitative (region of interest (ROI)/volume of interest (VOI) based) comparisons. In 43 patients, multi-TI PASL-GRASE showed perfusion alterations with moderate accuracy in the qualitative analysis. Quantitatively, moderate correlation coefficients were found for the MCA territory (ROI based: r=0.52, VOI based: r=0.48). In the anterior cerebral artery (ACA) territory, a readout related right-sided susceptibility artifact impaired correlation (ROI based: r=0.29, VOI based: r=0.34). Arterial transit delay artifacts were found only in 12% of patients. In conclusion, multi-TI PASL-GRASE can correct for arterial transit delay in patients with long ATTs. These results are promising for the transfer of ASL to the clinical practice.Journal of Cerebral Blood Flow & Metabolism advance online publication, 19 November 2014; doi:10.1038/jcbfm.2014.200.
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Bidirectional Relationships Between Client and Counselor Speech: The Importance of Reframing.
Psychol Addict Behav
PUBLISHED: 06-24-2014
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In the study of motivational interviewing (MI), counselor skill has been posited to influence client language about change or "change talk." This study investigates the relationship between a specific counselor behavior, valenced reflective listening, and client change talk in a MI intervention with substance-using adolescents. A combination of recorded in-person and telephone (n = 223) sessions were sequentially coded using the Motivational Interviewing Skill Code 2.5. Reflections were categorized by valence, meaning they included content that was either moving toward (i.e., positive reflection) or away from change (i.e., negative reflection). Client language was coded as either moving toward change, away from change, or neutral about change. Probability analyses showed positive reflections were 11 times more likely to be followed by change talk and 71% less likely to be followed by counter change talk. Negative reflections were 19 times more likely to be followed by counter change talk and 65% less likely to be followed by change talk. Client language was also predictive of counselor reflections, such that positive reflections were 10 times more likely to occur after client change talk and negative reflections were 19 times more likely to follow counter change talk. Because the percentage of change talk expressed in a session has been shown to be positively related to improved behavioral outcomes, counselors should avoid unintentional reflections of counter change talk and use reframing techniques to change the valence of client change language. Implications for MI practice and training are discussed. (PsycINFO Database Record (c) 2014 APA, all rights reserved).
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Anhedonia and the relative reward value of drug and nondrug reinforcers in cigarette smokers.
J Abnorm Psychol
PUBLISHED: 06-03-2014
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Anhedonia-a psychopathologic trait indicative of diminished interest, pleasure, and enjoyment-has been linked to use of and addiction to several substances, including tobacco. We hypothesized that anhedonic drug users develop an imbalance in the relative reward value of drug versus nondrug reinforcers, which could maintain drug use behavior. To test this hypothesis, we examined whether anhedonia predicted the tendency to choose an immediate drug reward (i.e., smoking) over a less immediate nondrug reward (i.e., money) in a laboratory study of non-treatment-seeking adult cigarette smokers. Participants (N = 275, ?10 cigarettes/day) attended a baseline visit that involved anhedonia assessment followed by 2 counterbalanced experimental visits: (a) after 16-hr smoking abstinence and (b) nonabstinent. At both experimental visits, participants completed self-report measures of mood state followed by a behavioral smoking task, which measured 2 aspects of the relative reward value of smoking versus money: (1) latency to initiate smoking when delaying smoking was monetarily rewarded and (2) willingness to purchase individual cigarettes. Results indicated that higher anhedonia predicted quicker smoking initiation and more cigarettes purchased. These relations were partially mediated by low positive and high negative mood states assessed immediately prior to the smoking task. Abstinence amplified the extent to which anhedonia predicted cigarette consumption among those who responded to the abstinence manipulation, but not the entire sample. Anhedonia may bias motivation toward smoking over alternative reinforcers, perhaps by giving rise to poor acute mood states. An imbalance in the reward value assigned to drug versus nondrug reinforcers may link anhedonia-related psychopathology to drug use.
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Depressive symptoms, negative urgency and substance use initiation in adolescents.
Drug Alcohol Depend
PUBLISHED: 05-22-2014
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Studies show depressive symptoms are associated with substance use in adolescents, but the mechanism underlying this association is still unclear. This study investigated negative urgency - the disposition to rash action during emotional states - as a factor explaining relations between depressive symptoms and use of several substances.
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The draft genome sequence of the ferret (Mustela putorius furo) facilitates study of human respiratory disease.
Nat. Biotechnol.
PUBLISHED: 05-20-2014
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The domestic ferret (Mustela putorius furo) is an important animal model for multiple human respiratory diseases. It is considered the 'gold standard' for modeling human influenza virus infection and transmission. Here we describe the 2.41 Gb draft genome assembly of the domestic ferret, constituting 2.28 Gb of sequence plus gaps. We annotated 19,910 protein-coding genes on this assembly using RNA-seq data from 21 ferret tissues. We characterized the ferret host response to two influenza virus infections by RNA-seq analysis of 42 ferret samples from influenza time-course data and showed distinct signatures in ferret trachea and lung tissues specific to 1918 or 2009 human pandemic influenza virus infections. Using microarray data from 16 ferret samples reflecting cystic fibrosis disease progression, we showed that transcriptional changes in the CFTR-knockout ferret lung reflect pathways of early disease that cannot be readily studied in human infants with cystic fibrosis disease.
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Alcohol, tobacco, and other drug misuse prevention and cessation programming for alternative high school youth: a review.
J Sch Health
PUBLISHED: 05-20-2014
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Relative to youth in regular high schools, alternative high school (AHS) youth are at high risk for alcohol, tobacco, and other drug (ATOD) misuse. Prevention and cessation efforts are needed for this population.
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Commentary--Project Towards No Drug Abuse: an evidence-based drug abuse prevention program.
J Prim Prev
PUBLISHED: 05-03-2014
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Project Towards No Drug Abuse (Project TND) is a research-based program that has been examined over seven group-randomized controlled trials. In all trials, an effect has been found on hard drug use. An effect has been found on alcohol use in four trials, and on cigarettes and marijuana in two trials. (Arguably, an effect is found on marijuana in three trials.) Program effects on violence-related behavior were established in earlier trials, though such effects were not assessed in later trials. Certainly, as in most scientific studies, there are limitations in the interpretation of the effects obtained, particularly regarding cigarette and marijuana use and violence-related behavior, and more empirical work is needed. For Project TND, however, numerous trial replications have been completed, and the effects within each trial could not have been obtained by chance alone more than 10 % of the time (two-tailed). These results suggest that Project TND is indeed evidence-based. To be evidence-based means that evidence has accumulated to suggest that the program is likely to work, at least under conditions that are comparable to those in which it has been tested.
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The NifTK software platform for image-guided interventions: platform overview and NiftyLink messaging.
Int J Comput Assist Radiol Surg
PUBLISHED: 04-28-2014
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To perform research in image-guided interventions, researchers need a wide variety of software components, and assembling these components into a flexible and reliable system can be a challenging task. In this paper, the NifTK software platform is presented. A key focus has been high-performance streaming of stereo laparoscopic video data, ultrasound data and tracking data simultaneously.
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Substance misuse prevention: addressing anhedonia.
New Dir Youth Dev
PUBLISHED: 04-23-2014
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Anhedonia refers to the inability of experiencing pleasure in positive life events. It has been conceptualized as a stable yet malleable characteristic and is associated with hypoactivity in the mesolimbic and mesocortical dopaminergic systems. Very recently, it has been posited as an etiologic factor associated with drug addiction onset, escalation, and relapse. Prevention programming could be developed to counteract the harmful impact of anhedonia, so as to minimize its impact on drug misuse. Remedial efforts are those that either (1) permit the individual to tolerate low levels of pleasure without resorting to drug misuse or other maladaptive behaviors that may unhealthily besot pleasure (for example, through normalization, structuring time, or meditation) or (2) counteract anhedonia by enhancing ones capability to experience pleasure (for example, behavioral activation, positive psychology, pharmacotherapy, or pursuit of positive addictions). School-based activities could be developed that can be completed by individuals, small workgroups, or the whole classroom. The concept of anhedonia is described in this chapter, and possible prevention strategies that might be utilized in schools as well as other contexts are discussed.
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Extending particle tracking capability with Delaunay triangulation.
Langmuir
PUBLISHED: 04-16-2014
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Particle tracking, the analysis of individual moving elements in time series of microscopic images, enables burgeoning new applications, but there is need to better resolve conformation and dynamics. Here we describe the advantages of Delaunay triangulation to extend the capabilities of particle tracking in three areas: (1) discriminating irregularly shaped objects, which allows one to track items other than point features; (2) combining time and space to better connect missing frames in trajectories; and (3) identifying shape backbone. To demonstrate the method, specific examples are given, involving analyzing the time-dependent molecular conformations of actin filaments and ?-DNA. The main limitation of this method, shared by all other clustering techniques, is the difficulty to separate objects when they are very close. This can be mitigated by inspecting locally to remove edges that are longer than their neighbors and also edges that link two objects, using methods described here, so that the combination of Delaunay triangulation with edge removal can be robustly applied to processing large data sets. As common software packages, both commercial and open source, can construct Delaunay triangulation on command, the methods described in this paper are both computationally efficient and easy to implement.
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The role of PET in the evaluation of musculoskeletal infections.
Semin Musculoskelet Radiol
PUBLISHED: 04-08-2014
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Musculoskeletal infections, particularly those in regions of complex anatomy and at postoperative sites, can be difficult to evaluate clinically, yet accurate diagnosis is essential to treat these infections promptly and correctly. Although anatomical imaging modalities are commonly used to diagnose musculoskeletal infections, the application of functional imaging through nuclear medicine techniques has long played a unique and important role in the evaluation of patients with suspected infections. In addition to the standard nuclear medicine single-photon emitting radiotracers traditionally used by nuclear medicine for planar and single-photon emission computed tomography infection imaging, in recent years we have seen a growth in the application of fluorodeoxyglucose (FDG) positron emission tomography (PET) and PET/CT applied to the detection and diagnosis of infection. In this review, we discuss the most common clinical scenarios in which musculoskeletal infection is suspected and for which FDG PET has been studied, in spinal, diabetic foot, and periprosthetic infections. We also highlight recent advances in new non-FDG PET radiotracers that may in the future enable better specificity for and characterization of musculoskeletal infections.
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Prevalence and co-occurrence of addictive behaviors among former alternative high school youth.
J Behav Addict
PUBLISHED: 04-05-2014
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Recent work has studied multiple addictions using a matrix measure, which taps multiple addictions through single responses for each type.
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Reconfigurable assemblies of Janus rods in AC electric fields.
Soft Matter
PUBLISHED: 03-22-2014
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We investigate the electric field-induced assembly of Janus colloids composed of silica rods patterned with gold patches in both side- and tip-coated motifs. These shape and chemically anisotropic particles assemble into reconfigurable chains, whose structure depends on patch location, AC electric field strength, and frequency.
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Even hard-sphere colloidal suspensions display Fickian yet non-Gaussian diffusion.
ACS Nano
PUBLISHED: 03-19-2014
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We scrutinize three decades of probability density displacement distribution in a simple colloidal suspension with hard-sphere interactions. In this index-matched and density-matched solvent, fluorescent tracer nanoparticles diffuse among matrix particles that are eight times larger, at concentrations from dilute to concentrated, over times up to when the tracer diffuses a few times its size. Displacement distributions of tracers, Gaussian in pure solvent, broaden systematically with increasing obstacle density. The onset of non-Gaussian dynamics is seen in even modestly dilute suspensions, which traditionally would be assumed to follow classic Gaussian expectation. The findings underscore, in agreement with recent studies of more esoteric soft matter systems, the prevalence of non-Gaussian yet Fickian diffusion.
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Expression of soluble and active interferon consensus in SUMO fusion expression system in E. coli.
Protein Expr. Purif.
PUBLISHED: 03-15-2014
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Protein production can be improved if methods for soluble protein expression are developed. Interferon consensus (IFN-con) is used to treat hepatitis C. IFN-con has superior activity compared to other clinically used interferon ? subtypes. However IFN-con is a challenging protein to produce in a soluble form using an Escherichia coli expression system. Here we describe the expression of soluble and active recombinant IFN-con in E. coli. The IFN-con gene sequence was optimised for expression in E. coli, which was then cloned into the Champion™ pET SUMO expression vector downstream of the SUMO fusion protein and under strong T7lac promoter. The SUMO-IFN-con fusion protein was efficiently expressed using the SHuffle™ E. coli strain and existed in soluble form as 86-88% of the total IFN-con. After removal of the SUMO fusion partner, approximately 50mg of recombinant IFN-con of at least 98% purity (by RP-HPLC) was obtained from a 1L fermentation culture. Using an A549/EMCV antiviral assay, the specific activity of the recombinant IFN-con was determined to be 960×10(6) IU/mg as calculated to NIBSC standard for IFN-con (3×10(5)pfu/mL virus titre). Comparison of the antiviral activity of the produced IFN-con to IFN ?-2a showed that IFN-con displays 2.8 times greater activity, which is in good agreement with what has been reported in the literature for pure protein. IFN-con expression in a soluble form from E. coli allowed us to use a simple, two-step purification process to yield highly pure and active IFN-con which is more efficient than obtaining IFN-con from inclusion bodies.
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A new reagent for stable thiol-specific conjugation.
Bioconjug. Chem.
PUBLISHED: 02-11-2014
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Many clinically used protein therapeutics are modified to increase their efficacy. Example modifications include the conjugation of cytotoxic drugs to monoclonal antibodies or poly(ethylene glycol) (PEG) to proteins and peptides. Monothiol-specific conjugation can be efficient and is often accomplished using maleimide-based reagents. However, maleimide derived conjugates are known to be susceptible to exchange reactions with endogenous proteins. To address this limitation in stability, we have developed PEG-mono-sulfone 3, which is a latently reactive, monothiol selective conjugation reagent. Comparative reactions with PEG-maleimide and other common thiol-selective PEGylation reagents including vinyl sulfone, acrylate, and halo-acetamides show that PEG-mono-sulfone 3 undergoes more efficient conjugation under mild reaction conditions. Due to the latent reactivity of PEG-mono-sulfone 3, its reactivity can be tailored and, once conjugated, the electron-withdrawing ketone is easily reduced under mild conditions to prevent undesirable deconjugation and exchange reactions from occurring. We describe a comparative stability study demonstrating a PEG-maleimide conjugate to be more labile to deconjugation than the corresponding conjugate obtained using PEG-mono-sulfone 3.
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Selective Janus particle assembly at tipping points of thermally-switched wetting.
Angew. Chem. Int. Ed. Engl.
PUBLISHED: 02-05-2014
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Thermal wetting can simply, selectively and reversibly join patchy particles into clusters (2D and 3D) and also colloidal crystals over the narrow temperature range of 1-2?°C. This is demonstrated with Janus particles (gold half-coated silica spheres) immersed in a binary mixture of water/2,6-lutidine, such that the relative strength of gold-gold bonding through hydrophobic interaction and silica-silica bonding through the wetting-induced attraction is reversibly switched according to temperature.
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Molecular imaging of urogenital diseases.
Semin Nucl Med
PUBLISHED: 02-04-2014
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There is an expanding and exciting repertoire of PET imaging radiotracers for urogenital diseases, particularly in prostate cancer, renal cell cancer, and renal function. Prostate cancer is the most commonly diagnosed cancer in men. With growing therapeutic options for the treatment of metastatic and advanced prostate cancer, improved functional imaging of prostate cancer beyond the limitations of conventional CT and bone scan is becoming increasingly important for both clinical management and drug development. PET radiotracers, apart from ¹?F-FDG, for prostate cancer are ¹?F-sodium fluoride, ¹¹C-choline, and ¹?F-fluorocholine, and (¹¹C-acetate. Other emerging and promising PET radiotracers include a synthetic l-leucine amino acid analogue (anti-¹?F-fluorocyclobutane-1-carboxylic acid), dihydrotestosterone analogue (¹?F-fluoro-5?-dihydrotestosterone), and prostate-specific membrane antigen-based PET radiotracers (eg, N-[N-[(S)-1,3-dicarboxypropyl]carbamoyl]-4-¹?F-fluorobenzyl-l-cysteine, ??Zr-DFO-J591, and ??Ga [HBED-CC]). Larger prospective and comparison trials of these PET radiotracers are needed to establish the role of PET/CT in prostate cancer. Although renal cell cancer imaging with FDG-PET/CT is available, it can be limited, especially for detection of the primary tumor. Improved renal cell cancer detection with carbonic anhydrase IX (CAIX)-based antibody (¹²?I-girentuximab) and radioimmunotherapy targeting with ¹??Lu-cG250 appear promising. Evaluation of renal injury by imaging renal perfusion and function with novel PET radiotracers include p-¹?F-fluorohippurate, hippurate m-cyano-p-¹?F-fluorohippurate, and rubidium-82 chloride (typically used for myocardial perfusion imaging). Renal receptor imaging of the renal renin-angiotensin system with a variety of selective PET radioligands is also becoming available for clinical translation.
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Emerging Adulthood: Developmental Period Facilitative of the Addictions.
Eval Health Prof
PUBLISHED: 02-03-2014
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Following adolescence and prior to young adulthood is a life developmental period that has been referred to as "emerging adulthood." This period of life involves an extended duration of learning and experimentation before settling into a career and stable relationship. Risky behaviors may be most tolerated or even promoted during emerging adulthood. Various substance and behavioral addictions are most likely to be realized during this period. Understanding what differentiates emerging adults that develop or do not develop full-blown addictions will assist in the creation of more efficacious prevention and cessation programs.
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From counselor skill to decreased marijuana use: does change talk matter?
J Subst Abuse Treat
PUBLISHED: 01-28-2014
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Client language about change, or change talk, is hypothesized to mediate the relationship between counselor fidelity in motivational interviewing (MI) and drug use outcomes. To investigate this causal chain, this study used data from an MI booster delivered to alternative high school students immediately after a universal classroom-based drug abuse prevention program. One hundred and seventy audio-recorded MI sessions about substance use were coded using the motivational interviewing skill code 2.5. Structural equation modeling showed that percentage of change talk on the part of the client mediated three of the four relationships between MI quality indicators and marijuana outcomes, while percentage of reflections of change talk showed a main effect of counselor skill on marijuana outcomes. Findings support change talk as an active ingredient of MI and provide new empirical support for the micro-skills of MI.
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Translating the link between social identity and health behavior into effective health communication strategies: An experimental application using antismoking advertisements.
Health Commun
PUBLISHED: 01-21-2014
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Social identity is a construct that has been linked to health behavior. Yet, limited research has attempted to translate this relationship into health communication strategies. The current study addresses this gap by examining the efficacy of social identity targeting (constructing ads so that they target a specific group with which an individual identifies) to increase anti-cigarette smoking beliefs among adolescents. Two hundred and fifty one adolescents aged 12-15, randomly selected from a nationally representative sample, completed an online survey. Participants indicated which of 11 peer groups (determined in pre-testing) they most identified with. Each participant was then randomly assigned to view an ad that either did or did not target that group. One week later participants reported level of agreement with two key antismoking beliefs presented in the ad. Multiple regression analyses indicated that if an individual identified with the group targeted by the ad, antismoking beliefs were more strongly endorsed. Based on these findings, we conclude that social identity targeting has the potential to increase the effectiveness of antismoking messages and should be considered when designing antismoking campaigns.
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Unorthodox bubbles when boiling in cold water.
Phys Rev E Stat Nonlin Soft Matter Phys
PUBLISHED: 01-15-2014
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High-speed movies are taken when bubbles grow at gold surfaces heated spotwise with a near-infrared laser beam heating water below the boiling point (60-70?°C) with heating powers spanning the range from very low to so high that water fails to rewet the surface after bubbles detach. Roughly half the bubbles are conventional: They grow symmetrically through evaporation until buoyancy lifts them away. Others have unorthodox shapes and appear to contribute disproportionately to heat transfer efficiency: mushroom cloud shapes, violently explosive bubbles, and cavitation events, probably stimulated by a combination of superheating, convection, turbulence, and surface dewetting during the initial bubble growth. Moreover, bubbles often follow one another in complex sequences, often beginning with an unorthodox bubble that stirs the water, followed by several conventional bubbles. This large dataset is analyzed and discussed with emphasis on how explosive phenomena such as cavitation induce discrepancies from classical expectations about boiling.
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A truncated FatB resulting from a single nucleotide insertion is responsible for reducing saturated fatty acids in maize seed oil.
Theor. Appl. Genet.
PUBLISHED: 01-13-2014
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We identified a G-nucleotide insertion in a maize FatB responsible for reducing saturated fatty acids through QTL mapping and map-based cloning and developed an allele-specific DNA marker for molecular breeding. Vegetable oils with reduced saturated fatty acids have signficant health benefits. SRS72NE, a Dow AgroSciences proprietory maize inbred line, was found to contain signficantly reduced levels of palmitic acid and total saturated fatty acids in seed oil when compared to other common inbreds. Using F2 and F3 populations derived from a cross between SRS72NE and a normal inbred SLN74, we have demonstrated that the reduced saturated fatty acid phenotype in SRS72NE is controlled by a single QTL on chromosome 9 that explains 79.1 % of palmitic acid and 79.6 % total saturated fatty acid variations. The QTL was mapped to an interval of 105 kb that contains one single gene, a type B fatty acyl-ACP thioesterase (ZmFatB; GRMZM5G829544). ZmFatB alleles from SRS72NE and common inbreds were cloned and sequenced. SRS72NE fatb allele contains a single nucleotide (G) insertion in the 6th exon, which creates a premature stop codon 22 base pairs down stream. As a result, ZmFatB protein from SRS72NE is predicted to contain eight altered and 90 deleted amino acids at its C-terminus. Because the affected region is part of the conserved acyl-ACP thioesterase catalytic domain, the truncated ZmFatB in SRS72NE is likely non-functional. We also show that fatb RNA level in SRS72NE is reduced by 4.4-fold when compared to the normal allele SNL74. A high throughput DNA assay capable of differentiating the normal and reduced saturate fatty acid alleles has been developed and can be used for accelerated molecular breeding.
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The Process of Adoption of Evidence-based Tobacco Use Prevention Programs in California Schools.
Prev Sci
PUBLISHED: 01-09-2014
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Although there are a number of research-validated substance use prevention programs available for wide-scale dissemination, very little is known about the factors that influence adoption of evidence-based prevention programs in schools. We tested a model of the mechanisms of program adoption in schools that was guided by diffusion of innovations and social ecological theories. Cross-sectional data were collected from a sample of school district and county office of education tobacco use prevention education coordinators throughout California. Structural equation modeling was used to test the effects of community and organizational variables on the adoption of prevention programs via school administrators' beliefs and the organization's receipt of funding for the program. Results supported the hypothesis that the process of adoption begins with forming beliefs about the program, leading to adoption through the receipt of funding. In addition, we found direct effects of various community- and organizational-level factors on beliefs, receipt of funding, and adoption. These results are likely to inform policies that affect school districts' use of evidence-based substance use prevention programming, which should ultimately lead to reductions in negative health outcomes among adolescents. Specifically, this study identifies various factors that could be targeted for improvement to enhance evidence-based program adoption. To our knowledge, this is the first study to empirically elucidate the process of adoption of evidence-based tobacco prevention programs in schools.
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Ex Vivo Response to Histone Deacetylase (HDAC) Inhibitors of the HIV Long Terminal Repeat (LTR) Derived from HIV-Infected Patients on Antiretroviral Therapy.
PLoS ONE
PUBLISHED: 01-01-2014
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Histone deacetylase inhibitors (HDACi) can induce human immunodeficiency virus (HIV) transcription from the HIV long terminal repeat (LTR). However, ex vivo and in vivo responses to HDACi are variable and the activity of HDACi in cells other than T-cells have not been well characterised. Here, we developed a novel assay to determine the activity of HDACi on patient-derived HIV LTRs in different cell types. HIV LTRs from integrated virus were amplified using triple-nested Alu-PCR from total memory CD4+ T-cells (CD45RO+) isolated from HIV-infected patients prior to and following suppressive antiretroviral therapy. NL4-3 or patient-derived HIV LTRs were cloned into the chromatin forming episomal vector pCEP4, and the effect of HDACi investigated in the astrocyte and epithelial cell lines SVG and HeLa, respectively. There were no significant differences in the sequence of the HIV LTRs isolated from CD4+ T-cells prior to and after 18 months of combination antiretroviral therapy (cART). We found that in both cell lines, the HDACi panobinostat, trichostatin A, vorinostat and entinostat activated patient-derived HIV LTRs to similar levels seen with NL4-3 and all patient derived isolates had similar sensitivity to maximum HDACi stimulation. We observed a marked difference in the maximum fold induction of luciferase by HDACi in HeLa and SVG, suggesting that the effect of HDACi may be influenced by the cellular environment. Finally, we observed significant synergy in activation of the LTR with vorinostat and the viral protein Tat. Together, our results suggest that the LTR sequence of integrated virus is not a major determinant of a functional response to an HDACi.
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Diffusion Tensor Imaging of Parkinson's Disease, Multiple System Atrophy and Progressive Supranuclear Palsy: A Tract-Based Spatial Statistics Study.
PLoS ONE
PUBLISHED: 01-01-2014
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Although often clinically indistinguishable in the early stages, Parkinson's disease (PD), Multiple System Atrophy (MSA) and Progressive Supranuclear Palsy (PSP) have distinct neuropathological changes. The aim of the current study was to identify white matter tract neurodegeneration characteristic of each of the three syndromes. Tract-based spatial statistics (TBSS) was used to perform a whole-brain automated analysis of diffusion tensor imaging (DTI) data to compare differences in fractional anisotropy (FA) and mean diffusivity (MD) between the three clinical groups and healthy control subjects. Further analyses were conducted to assess the relationship between these putative indices of white matter microstructure and clinical measures of disease severity and symptoms. In PSP, relative to controls, changes in DTI indices consistent with white matter tract degeneration were identified in the corpus callosum, corona radiata, corticospinal tract, superior longitudinal fasciculus, anterior thalamic radiation, superior cerebellar peduncle, medial lemniscus, retrolenticular and anterior limb of the internal capsule, cerebral peduncle and external capsule bilaterally, as well as the left posterior limb of the internal capsule and the right posterior thalamic radiation. MSA patients also displayed differences in the body of the corpus callosum corticospinal tract, cerebellar peduncle, medial lemniscus, anterior and superior corona radiata, posterior limb of the internal capsule external capsule and cerebral peduncle bilaterally, as well as the left anterior limb of the internal capsule and the left anterior thalamic radiation. No significant white matter abnormalities were observed in the PD group. Across groups, MD correlated positively with disease severity in all major white matter tracts. These results show widespread changes in white matter tracts in both PSP and MSA patients, even at a mid-point in the disease process, which are not found in patients with PD.
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Modelling Hen Harrier Dynamics to Inform Human-Wildlife Conflict Resolution: A Spatially-Realistic, Individual-Based Approach.
PLoS ONE
PUBLISHED: 01-01-2014
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Individual-based models have gained popularity in ecology, and enable simultaneous incorporation of spatial explicitness and population dynamic processes to understand spatio-temporal patterns of populations. We introduce an individual-based model for understanding and predicting spatial hen harrier (Circus cyaneus) population dynamics in Great Britain. The model uses a landscape with habitat, prey and game management indices. The hen harrier population was initialised according to empirical census estimates for 1988/89 and simulated until 2030, and predictions for 1998, 2004 and 2010 were compared to empirical census estimates for respective years. The model produced a good qualitative match to overall trends between 1989 and 2010. Parameter explorations revealed relatively high elasticity in particular to demographic parameters such as juvenile male mortality. This highlights the need for robust parameter estimates from empirical research. There are clearly challenges for replication of real-world population trends, but this model provides a useful tool for increasing understanding of drivers of hen harrier dynamics and focusing research efforts in order to inform conflict management decisions.
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A Phase 1 Study of 131I-CLR1404 in Patients with Relapsed or Refractory Advanced Solid Tumors: Dosimetry, Biodistribution, Pharmacokinetics, and Safety.
PLoS ONE
PUBLISHED: 01-01-2014
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131I-CLR1404 is a small molecule that combines a tumor-targeting moiety with a therapeutic radioisotope. The primary aim of this phase 1 study was to determine the administered radioactivity expected to deliver 400 mSv to the bone marrow. The secondary aims were to determine the pharmacokinetic (PK) and safety profiles of 131I-CLR1404.
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An empirical comparison of different approaches for combining multimodal neuroimaging data with support vector machine.
Front Neurosci
PUBLISHED: 01-01-2014
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In the pursuit of clinical utility, neuroimaging researchers of psychiatric and neurological illness are increasingly using analyses, such as support vector machine, that allow inference at the single-subject level. Recent studies employing single-modality data, however, suggest that classification accuracies must be improved for such utility to be realized. One possible solution is to integrate different data types to provide a single combined output classification; either by generating a single decision function based on an integrated kernel matrix, or, by creating an ensemble of multiple single modality classifiers and integrating their predictions. Here, we describe four integrative approaches: (1) an un-weighted sum of kernels, (2) multi-kernel learning, (3) prediction averaging, and (4) majority voting, and compare their ability to enhance classification accuracy relative to the best single-modality classification accuracy. We achieve this by integrating structural, functional, and diffusion tensor magnetic resonance imaging data, in order to compare ultra-high risk (n = 19), first episode psychosis (n = 19) and healthy control subjects (n = 23). Our results show that (i) whilst integration can enhance classification accuracy by up to 13%, the frequency of such instances may be limited, (ii) where classification can be enhanced, simple methods may yield greater increases relative to more computationally complex alternatives, and, (iii) the potential for classification enhancement is highly influenced by the specific diagnostic comparison under consideration. In conclusion, our findings suggest that for moderately sized clinical neuroimaging datasets, combining different imaging modalities in a data-driven manner is no "magic bullet" for increasing classification accuracy. However, it remains possible that this conclusion is dependent on the use of neuroimaging modalities that had little, or no, complementary information to offer one another, and that the integration of more diverse types of data would have produced greater classification enhancement. We suggest that future studies ideally examine a greater variety of data types (e.g., genetic, cognitive, and neuroimaging) in order to identify the data types and combinations optimally suited to the classification of early stage psychosis.
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DWI intensity values predict FLAIR lesions in acute ischemic stroke.
PLoS ONE
PUBLISHED: 01-01-2014
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In acute stroke, the DWI-FLAIR mismatch allows for the allocation of patients to the thrombolysis window (<4.5 hours). FLAIR-lesions, however, may be challenging to assess. In comparison, DWI may be a useful bio-marker owing to high lesion contrast. We investigated the performance of a relative DWI signal intensity (rSI) threshold to predict the presence of FLAIR-lesions in acute stroke and analyzed its association with time-from-stroke-onset.
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Dysconnectivity of neurocognitive networks at rest in very-preterm born adults.
Neuroimage Clin
PUBLISHED: 01-01-2014
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Advances in neonatal medicine have resulted in a larger proportion of preterm-born individuals reaching adulthood. Their increased liability to psychiatric illness and impairments of cognition and behaviour intimate lasting cerebral consequences; however, the central physiological disturbances remain unclear. Of fundamental importance to efficient brain function is the coordination and contextually-relevant recruitment of neural networks. Large-scale distributed networks emerge perinatally and increase in hierarchical complexity through development. Preterm-born individuals exhibit systematic reductions in correlation strength within these networks during infancy. Here, we investigate resting-state functional connectivity in functional magnetic resonance imaging data from 29 very-preterm (VPT)-born adults and 23 term-born controls. Neurocognitive networks were identified with spatial independent component analysis conducted using the Infomax algorithm and employing Icasso procedures to enhance component robustness. Network spatial focus and spectral power were not generally significantly affected by preterm birth. By contrast, Granger-causality analysis of the time courses of network activity revealed widespread reductions in between-network connectivity in the preterm group, particularly along paths including salience-network features. The potential clinical relevance of these Granger-causal measurements was suggested by linear discriminant analysis of topological representations of connection strength, which classified individuals by group with a maximal accuracy of 86%. Functional connections from the striatal salience network to the posterior default mode network informed this classification most powerfully. In the VPT-born group it was additionally found that perinatal factors significantly moderated the relationship between executive function (which was reduced in the VPT-born as compared with the term-born group) and generalised partial directed coherence. Together these findings show that resting-state functional connectivity of preterm-born individuals remains compromised in adulthood; and present consistent evidence that the striatal salience network is preferentially affected. Therapeutic practices directed at strengthening within-network cohesion and fine-tuning between-network inter-relations may have the potential to mitigate the cognitive, behavioural and psychiatric repercussions of preterm birth.
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Clinical evaluation of an arterial-spin-labeling product sequence in steno-occlusive disease of the brain.
PLoS ONE
PUBLISHED: 01-01-2014
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In brain perfusion imaging, arterial spin labeling (ASL) is a noninvasive alternative to dynamic susceptibility contrast-magnetic resonance imaging (DSC-MRI). For clinical imaging, only product sequences can be used. We therefore analyzed the performance of a product sequence (PICORE-PASL) included in an MRI software-package compared with DSC-MRI in patients with steno-occlusion of the MCA or ICA >70%.
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Colloidal-Sized Metal-Organic Frameworks: Synthesis and Applications.
Acc. Chem. Res.
PUBLISHED: 12-12-2013
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Colloidal metal-organic frameworks (CMOFs), nanoporous colloidal-sized crystals that are uniform in both size and polyhedral shape, are crystals composed of metal ions and organic bridging ligands, which can be used as building blocks for self-assembly in organic and aqueous liquids. They stand in contrast to conventional metal-organic frameworks (MOFs), which scientists normally study in the form of bulk crystalline powders. However, powder MOFs generally have random crystal size and shape and therefore do not possess either a definite mutual arrangement with adjacent particles or uniformity. CMOFs do have this quality, which can be important in vital uptake and release kinetics. In this Account, we present the diverse methods of synthesis, pore chemistry control, surface modification, and assembly techniques of CMOFs. In addition, we survey recent achievements and future applications in this emerging field. There is potential for a paradigm shift, away from using just bulk crystalline powders, towards using particles whose size and shape are regulated. The concept of colloidal MOFs takes into account that nanoporous MOFs, conventionally prepared in the form of bulk crystalline powders with random crystal size, shape, and orientation, may also form colloidal-sized objects with uniform size and morphology. Furthermore, the traditional MOF functions that depend on porosity present additional control over those MOF functions that depend on pore interactions. They also can enable controlled spatial arrangements between neighboring particles. To begin, we discuss progress regarding synthesis of MOF nano- and microcrystals whose crystal size and shape are well regulated. Next, we review the methods to modify the surfaces with dye molecules and polymers. Dyes are useful when seeking to observe nonluminescent CMOFs in situ by optical microscopy, while polymers are useful to tune their interparticle interactions. Third, we discuss criteria to assess the stability of CMOFs for various applications. In another section of this Account, we give examples of supracrystal assembly in liquid, on substrates, at interfaces, and under external electric fields. We end this Account with discussion of possible future developments, both conceptual and technological.
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Fab-PEG-Fab as a Potential Antibody Mimetic.
Bioconjug. Chem.
PUBLISHED: 11-04-2013
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IgG antibodies have evolved to be flexible so that they can bind to epitopes located over a wide spatial range. The two Fabs in an IgG antibody are linked together as if each Fab is at the end of a linear, flexible molecule. PEG was used as a scaffold molecule to link two Fabs together to give Fab-PEG-Fab molecules, or FpFs. Preparation of FpFs was achieved with reagents that undergo site-specific conjugation at each PEG terminus by bis-alkylation with the two cysteine thiols from a disulfide bond. This allowed each Fab to be conjugated to the PEG scaffold in essentially the same region that each Fab is linked in an IgG. Fabs were sourced directly (e.g., ranibizumab) or monoclonal IgG antibodies were proteolytically digested to obtain the Fabs. This allowed the resulting FpFs to be directly compared to parent IgGs. PEG scaffolds of 6, 10, and 20 kDa were used to make the corresponding FpFs. Dynamic light scatting data suggested the resulting FpFs were similar in size to an IgG antibody and about half the size of a 20 kDa PEGylated-Fab. The solution size of PEG-conjugated proteins is known to be dominated by the extended solution structure of PEG, so it is thought that the smaller size of the FpFs is due to interactions between the two Fabs. Anti-VEGF and anti-Her2 FpFs were prepared and evaluated. The FpFs displayed similar apparent affinities to their parent IgGs. Slower dissociation rates were observed for the anti-VEGF FpFs compared to bevacizumab. The anti-VEGF FpFs also displayed in vitro anti-angiogenic properties comparable to or better than bevacizumab. These first studies indicate that FpFs warrant further examination in a therapeutic indication where the presence of the Fc may not be required.
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Single-molecule observation of long jumps in polymer adsorption.
ACS Nano
PUBLISHED: 10-29-2013
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Single-molecule fluorescence imaging of adsorption onto initially bare surfaces shows that polymer chains need not localize immediately after arrival. In a system optimized to present limited adsorption sites (quartz surface to which polyethylene glycol (PEG) chains adsorb from aqueous solution at pH 8.2), we find that some chains diffuse back into bulk solution and readsorb at some distance away, sometimes multiple times before they either localize at a stable position or diffuse away into bulk solution. This mechanism of surface diffusion is considerably more rapid than the classical model in which adsorbed polymers crawl on surfaces while the entire molecule remains adsorbed, suggesting the conceptual generality of a recent report ( Phys. Rev. Lett. 2013 , 110 , 256101 ) but in a new experimental system and with comparison of different chain lengths. We find the trajectories with jumps to follow a truncated Lévy distribution of step size with limiting slope -2.5, consistent with a well-defined, rapid surface diffusion coefficient over the times we observe. The broad waiting time distribution appears to reflect that polymer chains possess a broad distribution of bound fraction: the smaller the bound fraction of a given chain, the shorter the surface residence time before executing the next surface jump.
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Translational Molecular Imaging of Prostate Cancer.
Curr Radiol Rep
PUBLISHED: 10-26-2013
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Prostate cancer is a heterogeneous disease, and its management is now evolving to become more personalized and to incorporate new targeted therapies. With these new changes comes a demand for molecular imaging techniques that can not only detect disease but also assess biology and treatment response. This review article summarizes current molecular imaging approaches in prostate cancer (e.g. (99m)Tc bone scintigraphy and (18)F-fluorodeoxyglucose positron emission tomography) and highlights emerging clinical and preclinical imaging agents, with an emphasis on mechanism and clinical application. Emerging agents at various stages of clinical translation include radiolabeled analogs of lipid, amino acid, and nucleoside metabolism, as well as agents more specifically targeting prostate cancer biomarkers including androgen receptor, prostate-specific membrane antigen and others. We also highlight new techniques and targeted contrast agents for magnetic resonance imaging and spectroscopy. For all these imaging techniques, a growing and important unmet need is for well-designed prospective clinical trials to establish clear indications with clinical benefit in prostate cancer.
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Molecular dynamic simulations of ocular tablet dissolution.
J Chem Inf Model
PUBLISHED: 10-21-2013
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Small tablets for implantation into the subconjunctival space in the eye are being developed to inhibit scarring after glaucoma filtration surgery (GFS). There is a need to evaluate drug dissolution at the molecular level to determine how the chemical structure of the active may correlate with dissolution in the nonsink conditions of the conjunctival space. We conducted molecular dynamics simulations to study the dissolution process of tablets derived from two drugs that can inhibit fibrosis after GFS, 5-fluorouracil (5-FU) and the matrix metalloprotease inhibitor (MMPi), ilomastat. The dissolution was simulated in the presence of simple point charge (SPC) water molecules, and the liquid turnover of the aqueous humor in the subconjunctival space was simulated by removal of the dissolved drug molecules at regular intervals and replacement by new water molecules. At the end of the simulation, the total molecular solvent accessible surface area of 5-FU tablets increased by 60 times more than that of ilomastat as a result of tablet swelling and release of molecules into solution. The tablet dissolution pattern shown in our molecular dynamic simulations tends to correlate with experimental release profiles. This work indicates that a series of molecular dynamic simulations can be used to predict the influence of the molecular properties of a drug on its dissolution profile and could be useful during preformulation where sufficient amounts of the drug are not always available to perform dissolution studies.
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Relative Effects of Social Self-Control, Sensation Seeking, and Impulsivity on Future Cigarette Use in a Sample of High-Risk Adolescents.
Subst Use Misuse
PUBLISHED: 10-04-2013
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We used confirmatory factor analysis to compare convergence/divergence across self-report measures of social self-control, sensation seeking, and impulsivity in a sample of high-risk adolescents. In addition, we tested baseline social self-control as a predictor of cigarette use one year later, controlling for baseline cigarette use, impulsivity/sensation seeking, and demographic variables. Data were collected in 2004-2005 from 821 adolescents (M age = 16.3; SD = 1.36) enrolled in 14 continuation high schools in Southern California. Of the baseline sample, 566 students participated in a follow-up survey one year later. Results indicated that social self-control represents a unique dimension of self-control and is a salient predictor of future cigarette use.
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Cultural and Social Influences on Adolescent Smoking Dissipate by Emerging Adulthood Among Hispanics in Southern California.
J Immigr Minor Health
PUBLISHED: 09-24-2013
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The aim of the present study was to identify risk factors for smoking among Hispanic adolescents and determine whether these factors continued to influence smoking into emerging adulthood. Data were drawn from 932 Hispanics in the greater Los Angeles area who were surveyed in high school in 2007 and then again in emerging adulthood from 2010 to 2012. Logistic regression assessed the associations between predictors in adolescence and smoking in adolescence while an order one transition logistic model assessed predictors in adolescence and smoking in emerging adulthood. Adult and sibling smoking status, perceptions of smoking, perceived discrimination, and fatalism all influenced smoking in adolescence but not in emerging adulthood. Once Hispanics reach emerging adulthood different tactics to reduce smoking will be needed and are where future research should be directed.
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Spirituality in addictions treatment: wisdom to know…what it is.
Subst Use Misuse
PUBLISHED: 09-18-2013
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Spirituality has long been integrated into treatments for addiction. However, how spirituality differs from other related constructs and implications for recovery among nonspiritual persons remains a source of discussion. This article examines ways in which spirituality is delineated, identifies variables that might mediate the relations between spirituality and recovery from substance abuse disorders, describes distinctions between spiritual and nonspiritual facets of addictions treatment, and suggests means to assist in further clarification of this construct.
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Shape-selected colloidal MOF crystals for aqueous use.
Chem. Commun. (Camb.)
PUBLISHED: 09-11-2013
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Methods are described to synthesize shape-selectable, monodisperse, aqueous-stable metal-organic frameworks (MOFs) by the reaction of aluminium nitrate with benzene tricarboxylic acid in various aqueous solvent mixtures and acetic acid as the capping ligand. Environmental stability was confirmed by thermal analysis and immersion in aqueous acidic media.
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Diagnosing heterogeneous dynamics in single-molecule/particle trajectories with multiscale wavelets.
ACS Nano
PUBLISHED: 08-23-2013
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We describe a simple automated method to extract and quantify transient heterogeneous dynamical changes from large data sets generated in single-molecule/particle tracking experiments. Based on wavelet transform, the method transforms raw data to locally match dynamics of interest. This is accomplished using statistically adaptive universal thresholding, whose advantage is to avoid a single arbitrary threshold that might conceal individual variability across populations. How to implement this multiscale method is described, focusing on local confined diffusion separated by transient transport periods or hopping events, with three specific examples: in cell biology, biotechnology, and glassy colloid dynamics. The discussion is generalized within the framework of continuous time random walk. This computationally efficient method can run routinely on hundreds of millions of data points analyzed within an hour on a desktop personal computer.
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Induction of antigen-positive cell death by the expression of Perforin, but not DTa, from a DNA vaccine enhances the immune response.
Immunol. Cell Biol.
PUBLISHED: 08-07-2013
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The failure of traditional protein-based vaccines to prevent infection by viruses such as HIV or hepatitis C highlights the need for novel vaccine strategies. DNA vaccines have shown promise in small animal models, and are effective at generating anti-viral T cell-mediated immune responses; however, they have proved to be poorly immunogenic in clinical trials. We propose that the induction of necrosis will enhance the immune response to vaccine antigens encoded by DNA vaccines, as necrotic cells are known to release a range of intracellular factors that lead to dendritic cell (DC) activation and enhanced cross-presentation of antigen. Here we provide evidence that induction of cell death in DNA vaccine-targeted cells provides an adjuvant effect following intradermal vaccination of mice; however, this enhancement of the immune response is dependent on both the mechanism and timing of cell death after antigen expression. We report that a DNA vaccine encoding the cytolytic protein, perforin, resulted in DC activation, enhanced broad and multifunctional CD8 T-cell responses to the HIV-1 antigen GAG and reduced viral load following challenge with a chimeric virus, EcoHIV, compared with the canonical GAG DNA vaccine. This effect was not observed for a DNA vaccine encoding an apoptosis-inducing toxin, DTa, or when the level of perforin expression was increased to induce cell death sooner after vaccination. Thus, inducing lytic cell death following a threshold level of expression of a viral antigen can improve the immunogenicity of DNA vaccines, whereas apoptotic cell death has an inhibitory effect on the immune response.Immunology and Cell Biology advance online publication, 10 December 2013; doi:10.1038/icb.2013.93.
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The Effects of Implementation Fidelity in the Towards No Drug Abuse Dissemination Trial.
Am J Health Educ
PUBLISHED: 07-03-2013
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The current study examines the influence of contextual and provider-level factors on the implementation fidelity of a research-based substance abuse prevention program. Also, it investigates whether two provider-level factors, self-efficacy and beliefs about the value of the program, statistically moderate and mediate the effects of a provider training intervention on implementation fidelity.
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Self-regulation of the anterior insula: Reinforcement learning using real-time fMRI neurofeedback.
Neuroimage
PUBLISHED: 06-27-2013
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The anterior insula (AI) plays a key role in affective processing, and insular dysfunction has been noted in several clinical conditions. Real-time functional MRI neurofeedback (rtfMRI-NF) provides a means of helping people learn to self-regulate activation in this brain region. Using the Blood Oxygenated Level Dependant (BOLD) signal from the right AI (RAI) as neurofeedback, we trained participants to increase RAI activation. In contrast, another group of participants was shown control feedback from another brain area. Pre- and post-training affective probes were shown, with subjective ratings and skin conductance response (SCR) measured. We also investigated a reward-related reinforcement learning model of rtfMRI-NF. In contrast to the controls, we hypothesised a positive linear increase in RAI activation in participants shown feedback from this region, alongside increases in valence ratings and skin conductance response (SCR) to affective probes. Hypothesis-driven analyses showed a significant interaction between the RAI/control neurofeedback groups and the effect of self-regulation. Whole-brain analyses revealed a significant linear increase in RAI activation across four training runs in the group who received feedback from RAI. Increased activation was also observed in the caudate body and thalamus, likely representing feedback-related learning. No positive linear trend was observed in the RAI in the group receiving control feedback, suggesting that these data are not a general effect of cognitive strategy or control feedback. The control group did, however, show diffuse activation across the putamen, caudate and posterior insula which may indicate the representation of false feedback. No significant training-related behavioural differences were observed for valence ratings, or SCR. In addition, correlational analyses based on a reinforcement learning model showed that the dorsal anterior cingulate cortex underpinned learning in both groups. In summary, these data demonstrate that it is possible to regulate the RAI using rtfMRI-NF within one scanning session, and that such reward-related learning is mediated by the dorsal anterior cingulate.
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Acculturation, social self-control, and substance use among Hispanic adolescents.
Psychol Addict Behav
PUBLISHED: 06-17-2013
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It is unclear how acculturation is related to self-control characteristics and whether part of the effect of acculturation on Hispanic adolescents substance use behavior is mediated through lower self-control. We tested social self-control, peer substance use, and baseline substance use as mediators of the effect of Hispanic (predominantly Mexican or Mexican American) adolescents level of U.S. acculturation on their substance use behavior 1 year later. In addition, we tested gender as a possible moderator of the pathways involved in the mediation model. Participants included 1,040 self-identified Hispanic/Latino adolescents (M = 14.7; SD = 0.90; 89% Mexican/Mexican American) recruited from nine public high schools. Acculturation was measured in terms of adolescents extent of English language use in general, at home, with friends, and their use of the English-language entertainment media. Analyses were conducted using structural equation modeling and controlled for potential confounders such as age and parental education. Results indicated a statistically significant three-path mediation in which poor social self-control and peer substance use mediated the effects of acculturation on prospective substance use. Paths in the mediation model were not found to differ by gender. Our findings suggest that acculturation may influence adolescents self-control characteristics related to interpersonal functioning, which may in turn influence their affiliation with substance-using friends and substance use behavior. Implications of the findings are discussed in terms of future research and prevention programming.
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Bidirectional associations between future time perspective and substance use among continuation high-school students.
Subst Use Misuse
PUBLISHED: 06-10-2013
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We examined whether a bidirectional, longitudinal relationship exists between future time perspective (FTP), measured with the Zimbardo Time Perspective Inventory, and any past 30-day use of alcohol, tobacco, marijuana, or hard drugs among continuation high school students (N = 1,310, mean age 16.8 years) in a large urban area. We found increased FTP to be protective against drug use for all substances except alcohol. While any baseline use of substances did not predict changes in FTP 1 year later. The discussion explores why alcohol findings may differ from other substances. Future consideration of FTP as a mediator of program effects is explored.
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Bursts of active transport in living cells.
Phys. Rev. Lett.
PUBLISHED: 06-05-2013
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We show, using a large new data set, that the temporally resolved speed of active cargo transport in living cells follows a scaling law over several decades of time and length. The statistical regularities display a time-averaged shape that we interpret to reflect stress buildup, followed by rapid release. The scaling power law agrees quantitatively with those reported in inanimate systems (jammed colloids and granular media, and magnetic Barkhausen noise), suggesting a common origin in pushing through a crowded environment in a weak force regime. The implied regulation of the speed of active cellular transport due to environmental obstruction results in bursts of speed and acceleration. These findings extend the classical notion of molecular crowding.
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Detection and localization of carcinoma within the prostate using high resolution transrectal gamma imaging (TRGI) of monoclonal antibody directed at prostate specific membrane antigen (PSMA)--proof of concept and initial imaging results.
Eur J Radiol
PUBLISHED: 06-03-2013
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Molecular imaging methods may identify primary prostate cancer foci and potentially guide biopsy and optimal management approaches. In this exploratory study, safety and first human imaging experience of a novel solid state endocavity transrectal gamma-imaging (TRGI) device was evaluated.
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Near-incompressible faceted polymer microcapsules from metal-organic framework templates.
Adv. Mater. Weinheim
PUBLISHED: 05-29-2013
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Faceted polymer microcapsules are prepared from metal-organic framework (MOF) templates. The MOF templates are removable under mild aqueous conditions. The obtained microcapsules are stiffer than their spherical counterparts, reflecting the near-incompressibility of the facet edges, and indicating that the faceting might be a useful strategy for controlling the mechanical properties of polymer microcapsules.
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The duck genome and transcriptome provide insight into an avian influenza virus reservoir species.
Nat. Genet.
PUBLISHED: 05-08-2013
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The duck (Anas platyrhynchos) is one of the principal natural hosts of influenza A viruses. We present the duck genome sequence and perform deep transcriptome analyses to investigate immune-related genes. Our data indicate that the duck possesses a contractive immune gene repertoire, as in chicken and zebra finch, and this repertoire has been shaped through lineage-specific duplications. We identify genes that are responsive to influenza A viruses using the lung transcriptomes of control ducks and ones that were infected with either a highly pathogenic (A/duck/Hubei/49/05) or a weakly pathogenic (A/goose/Hubei/65/05) H5N1 virus. Further, we show how the ducks defense mechanisms against influenza infection have been optimized through the diversification of its ?-defensin and butyrophilin-like repertoires. These analyses, in combination with the genomic and transcriptomic data, provide a resource for characterizing the interaction between host and influenza viruses.
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Modular stitching to image single-molecule DNA transport.
J. Am. Chem. Soc.
PUBLISHED: 04-15-2013
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For study of time-dependent conformation, all previous single-molecule imaging studies of polymer transport involve fluorescence labeling uniformly along the chain, which suffers from limited resolution due to the diffraction limit. Here we demonstrate the concept of submolecular single-molecule imaging with DNA chains assembled from DNA fragments such that a chain is labeled at designated spots with covalently attached fluorescent dyes and the chain backbone with dyes of different color. High density of dyes ensures good signal-to-noise ratio to localize the designated spots in real time with nanometer precision and prevents significant photobleaching for long-time tracking purposes. To demonstrate usefulness of this approach, we image electrophoretic transport of ?-DNA through agarose gels. The unexpected pattern is observed that one end of each molecule tends to stretch out in the electric field while the other end remains quiescent for some time before it snaps forward and the stretch-recoil cycle repeats. These features are neither predicted by prevailing theories of electrophoresis mechanism nor detectable by conventional whole-chain labeling methods, which demonstrate pragmatically the usefulness of modular stitching to reveal internal chain dynamics of single molecules.
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The draft genomes of soft-shell turtle and green sea turtle yield insights into the development and evolution of the turtle-specific body plan.
Nat. Genet.
PUBLISHED: 03-27-2013
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The unique anatomical features of turtles have raised unanswered questions about the origin of their unique body plan. We generated and analyzed draft genomes of the soft-shell turtle (Pelodiscus sinensis) and the green sea turtle (Chelonia mydas); our results indicated the close relationship of the turtles to the bird-crocodilian lineage, from which they split ?267.9-248.3 million years ago (Upper Permian to Triassic). We also found extensive expansion of olfactory receptor genes in these turtles. Embryonic gene expression analysis identified an hourglass-like divergence of turtle and chicken embryogenesis, with maximal conservation around the vertebrate phylotypic period, rather than at later stages that show the amniote-common pattern. Wnt5a expression was found in the growth zone of the dorsal shell, supporting the possible co-option of limb-associated Wnt signaling in the acquisition of this turtle-specific novelty. Our results suggest that turtle evolution was accompanied by an unexpectedly conservative vertebrate phylotypic period, followed by turtle-specific repatterning of development to yield the novel structure of the shell.
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What is Visualize?

JoVE Visualize is a tool created to match the last 5 years of PubMed publications to methods in JoVE's video library.

How does it work?

We use abstracts found on PubMed and match them to JoVE videos to create a list of 10 to 30 related methods videos.

Video X seems to be unrelated to Abstract Y...

In developing our video relationships, we compare around 5 million PubMed articles to our library of over 4,500 methods videos. In some cases the language used in the PubMed abstracts makes matching that content to a JoVE video difficult. In other cases, there happens not to be any content in our video library that is relevant to the topic of a given abstract. In these cases, our algorithms are trying their best to display videos with relevant content, which can sometimes result in matched videos with only a slight relation.