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Find video protocols related to scientific articles indexed in Pubmed.
Ras pathway mutations are highly prevalent in relapsed childhood acute lymphoblastic leukaemia, may act as relapse-drivers and confer sensitivity to MEK inhibition.
Blood
PUBLISHED: 09-26-2014
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For most children who relapse with acute lymphoblastic leukaemia, the prognosis is poor and there is a need for novel therapies to improve outcome. We screened samples from children with B lineage ALL entered into the ALL-REZ BFM 2002 clinical trial (ClinicalTrials.gov identifier: NCT00114348) for somatic mutations activating the Ras pathway (KRAS, NRAS, FLT3 and PTPN11) and showed mutation to be highly prevalent (76 from 206). Clinically, they were associated with high risk features including early relapse, CNS involvement and specifically for NRAS/KRAS mutations, chemoresistance. KRAS mutations were associated with a reduced overall survival. Mutation screening of the matched diagnostic samples found many to be wildtype but using more sensitive allelic specific assays, low level mutated subpopulations were found in many cases, suggesting that they survived up front therapy and subsequently emerged at relapse. Preclinical evaluation of the MEK1/2 inhibitor, selumetinib (AZD6244, ARRY-142886) showed significant differential sensitivity in Ras pathway mutated ALL compared to wild type cells both in vitro and in a orthotopic xenograft model engrafted with primary ALL and in the latter, reduced RAS mutated CNS leukaemia. Given these data, clinical evaluation of selumetinib may be warranted for Ras pathway mutated relapsed ALL.
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Preservation of donor hearts using hypothermic oxygenated perfusion.
Ann. Transplant.
PUBLISHED: 08-20-2014
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Hypothermic machine perfusion of donor hearts enables continuous aerobic metabolism and washout of toxic metabolic byproducts. We evaluated the effect of machine perfusion on cardiac myocyte integrity in hearts preserved for 4 h in a novel device that provides pulsatile oxygenated hypothermic perfusion (Paragonix Sherpa Perfusion™ Cardiac Transport System).
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A meta-analysis of endoscopic versus conventional open radial artery harvesting for coronary artery bypass graft surgery.
Innovations (Phila)
PUBLISHED: 08-02-2014
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The radial artery has been demonstrated to provide superior long-term patency outcomes compared with saphenous veins for selected patients who undergo coronary artery bypass graft surgery. Recently, endoscopic radial artery harvesting has been popularized to improve cosmetic and perioperative outcomes. However, concerns have been raised regarding the effects on long-term survival and graft patency of this relatively novel technique. The present meta-analysis aimed to assess the safety and the efficacy of endoscopic radial artery harvesting versus the conventional open approach.
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Telomere dysfunction accurately predicts clinical outcome in chronic lymphocytic leukaemia, even in patients with early stage disease.
Br. J. Haematol.
PUBLISHED: 03-26-2014
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Defining the prognosis of individual cancer sufferers remains a significant clinical challenge. Here we assessed the ability of high-resolution single telomere length analysis (STELA), combined with an experimentally derived definition of telomere dysfunction, to predict the clinical outcome of patients with chronic lymphocytic leukaemia (CLL). We defined the upper telomere length threshold at which telomere fusions occur and then used the mean of the telomere 'fusogenic' range as a prognostic tool. Patients with telomeres within the fusogenic range had a significantly shorter overall survival (P < 0·0001; Hazard ratio [HR] = 13·2, 95% confidence interval [CI] = 11·6-106·4) and this was preserved in early-stage disease patients (P < 0·0001, HR=19·3, 95% CI = 17·8-802·5). Indeed, our assay allowed the accurate stratification of Binet stage A patients into those with indolent disease (91% survival at 10 years) and those with poor prognosis (13% survival at 10 years). Furthermore, patients with telomeres above the fusogenic mean showed superior prognosis regardless of their IGHV mutation status or cytogenetic risk group. In keeping with this finding, telomere dysfunction was the dominant variable in multivariate analysis. Taken together, this study provides compelling evidence for the use of high-resolution telomere length analysis coupled with a definition of telomere dysfunction in the prognostic assessment of CLL.
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Supercoiling in DNA and chromatin.
Curr. Opin. Genet. Dev.
PUBLISHED: 03-04-2014
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Supercoiling is a fundamental property of DNA and chromatin. It is modulated by polymerase and topoisomerase activities and, through regulated constraint, by DNA/chromatin binding proteins. As a non-covalent and elusive topological modification, supercoiling has proved intractable to research despite being a crucial regulator of nuclear structure and function. Recent studies have improved our understanding of the formation, regulation and organisation of supercoiling domains in vivo, and reinforce the prospect that the propagation of supercoiling can influence local and global chromatin structure. However, to further our understanding the development of new experimental tools and models are required to better dissect the mechanics of this key topological regulator.
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A phase I and pharmacokinetic study of capecitabine in combination with radiotherapy in patients with localised inoperable pancreatic cancer.
Cancer Chemother. Pharmacol.
PUBLISHED: 02-26-2014
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The purpose of this phase I study was to determine the safety, toxicity, maximum tolerated dose, and pharmacokinetics of capecitabine when administered concurrently with radiotherapy in patients with localised, inoperable pancreatic adenocarcinoma.
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Distally-based osteocutaneous dorsal metatarsal artery flap for hallux reconstruction.
J Plast Reconstr Aesthet Surg
PUBLISHED: 01-10-2014
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Reconstruction of complex defects of the distal portion of the foot remains a challenging problem for plastic surgeons. A traumatic case is presented where reconstruction of a complex plantar defect of the hallux was achieved using a distally-based osteocutaneous metatarsal artery flap based on the second dorsal metatarsal artery. Local flap repair is a viable reconstructive option for complex defects of the plantar surface of the forefoot.
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Second malignant neoplasms and cardiovascular disease following radiotherapy.
Health Phys
PUBLISHED: 01-01-2014
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Second malignant neoplasms (SMNs) and cardiovascular disease (CVD) are among the most serious and life-threatening late adverse effects experienced by the growing number of cancer survivors worldwide and are due in part to radiotherapy. The National Council on Radiation Protection and Measurements (NCRP) convened an expert scientific committee to critically and comprehensively review associations between radiotherapy and SMNs and CVD, taking into account radiobiology; genomics; treatment (i.e., radiotherapy with or without chemotherapy and other therapies); type of radiation; and quantitative considerations (i.e., dose-response relationships). Major conclusions of the NCRP include: (1) the relevance of older technologies for current risk assessment when organ-specific absorbed dose and the appropriate relative biological effectiveness are taken into account and (2) the identification of critical research needs with regard to newer radiation modalities, dose-response relationships, and genetic susceptibility. Recommendation for research priorities and infrastructural requirements include (1) long-term large-scale follow-up of extant cancer survivors and prospectively treated patients to characterize risks of SMNs and CVD in terms of radiation dose and type; (2) biological sample collection to integrate epidemiological studies with molecular and genetic evaluations; (3) investigation of interactions between radiotherapy and other potential confounding factors, such as age, sex, race, tobacco and alcohol use, dietary intake, energy balance, and other cofactors, as well as genetic susceptibility; (4) focusing on adolescent and young adult cancer survivors, given the sparse research in this population; and (5) construction of comprehensive risk prediction models for SMNs and CVD to permit the development of follow-up guidelines and prevention and intervention strategies.
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Restless Mind, Restless Body.
J Exp Psychol Learn Mem Cogn
PUBLISHED: 12-23-2013
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In the present work, we investigate the hypothesis that failures of task-related executive control that occur during episodes of mind wandering are associated with an increase in extraneous movements (fidgeting). In 2 studies, we assessed mind wandering using thought probes while participants performed the metronome response task (MRT), which required them to synchronize button presses with tones. Participants performed this task while sitting on a Wii Balance Board providing us with an index of fidgeting. Results of Study 1 demonstrate that relative to on-task periods, mind wandering is indeed accompanied by increases in fidgeting, as well as increased response variability in the MRT. In Study 2, we observed that only deep mind wandering was associated with increases in fidgeting, whereas task-related response variability increased even during mild mind wandering. We interpret these findings in the context of current theories of mind wandering and suggest that (a) mind wandering is associated with costs not only to primary-task performance but also to secondary-task goals (e.g., controlling extraneous movements) and (b) these costs may depend on the degree to which task-related executive control processes are disengaged during mind wandering (i.e., depth of mind wandering). (PsycINFO Database Record (c) 2013 APA, all rights reserved).
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Enduring legacy of a toxic fan via episodic redistribution of California gold mining debris.
Proc. Natl. Acad. Sci. U.S.A.
PUBLISHED: 10-28-2013
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The interrelationships between hydrologically driven evolution of legacy landscapes downstream of major mining districts and the contamination of lowland ecosystems are poorly understood over centennial time scales. Here, we demonstrate within piedmont valleys of Californias Sierra Nevada, through new and historical data supported by modeling, that anthropogenic fans produced by 19th century gold mining comprise an episodically persistent source of sediment-adsorbed Hg to lowlands. Within the enormous, iconic Yuba Fan, we highlight (i) an apparent shift in the relative processes of fan evolution from gradual vertical channel entrenchment to punctuated lateral erosion of fan terraces, thus enabling entrainment of large volumes of Hg-laden sediment during individual floods, and (ii) systematic intrafan redistribution and downstream progradation of fan sediment into the Central Valley, triggered by terrace erosion during increasingly long, 10-y flood events. Each major flood apparently erodes stored sediment and delivers to sensitive lowlands the equivalent of ~10-30% of the entire postmining Sierran Hg mass so far conveyed to the San Francisco Bay-Delta (SFBD). This process of protracted but episodic erosion of legacy sediment and associated Hg is likely to persist for >10(4) y. It creates, within an immense swath of river corridor well upstream of the SFBD, new contaminated floodplain surfaces primed for Hg methylation and augments/replenishes potential Hg sources to the SFBD. Anticipation, prediction, and management of toxic sediment delivery, and corresponding risks to lowland ecology and human society globally, depend on the morphodynamic stage of anthropogenic fan evolution, synergistically coupled to changing frequency of and duration extreme floods.
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A systematic review and meta-analysis of surgical treatments for malignant pleural mesothelioma.
Lung Cancer
PUBLISHED: 09-10-2013
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Malignant pleural mesothelioma (MPM) is an aggressive disease of the pleural lining with a dismal prognosis. Surgical treatments of MPM with a curative intent include extrapleural pneumonectomy and extended pleurectomy/decortication (P/D). This meta-analysis aimed to compare the perioperative and long-term outcomes of EPP and extended P/D for selected surgical candidates.
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A methodological note on evaluating performance in a sustained-attention-to-response task.
Behav Res Methods
PUBLISHED: 09-05-2013
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We evaluated the influence of speed-accuracy trade-offs on performance in the sustained attention to response task (SART), a task often used to evaluate the effectiveness of techniques designed to improve sustained attention. In the present study, we experimentally manipulated response delay in a variation of the SART and found that commission errors, which are commonly used as an index of lapses in sustained attention, were a systematic function of manipulated differences in response delay. Delaying responses to roughly 800 ms after stimulus onset reduced commission errors substantially. We suggest the possibility that any technique that affects response speed will indirectly alter error rates independently of improvements in sustained attention. Investigators therefore need to carefully explore, report, and correct for changes in response speed that accompany improvements in performance or, alternatively, to employ tasks that control for response speed.
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Variation at 10p12.2 and 10p14 influences risk of childhood B-cell acute lymphoblastic leukemia and phenotype.
Blood
PUBLISHED: 08-30-2013
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Acute lymphoblastic leukemia (ALL) is the major pediatric cancer diagnosed in economically developed countries with B-cell precursor (BCP)-ALL, accounting for approximately 70% of ALL. Recent genome-wide association studies (GWAS) have provided the first unambiguous evidence for common inherited susceptibility to BCP-ALL, identifying susceptibility loci at 7p12.2, 9p21.3, 10q21.2, and 14q11.2. To identify additional BCP-ALL susceptibility loci, we conducted a GWAS and performed a meta-analysis with a published GWAS totaling 1658 cases and 4723 controls, with validation in 1449 cases and 1488 controls. Combined analysis identified novel loci mapping to 10p12.2 (rs10828317, odds ratio [OR] = 1.23; P = 2.30 × 10(-9)) and 10p14 marked by rs3824662 (OR = 1.31; P = 8.62 × 10(-12)). The single nucleotide polymorphism rs10828317 is responsible for the N215S polymorphism in exon 7 of PIP4K2A, and rs3824662 localizes to intron 3 of the transcription factor and putative tumor suppressor gene GATA3. The rs10828317 association was shown to be specifically associated with hyperdiploid ALL, whereas the rs3824662-associated risk was confined to nonhyperdiploid non-TEL-AML1 + ALL. The risk allele of rs3824662 was correlated with older age at diagnosis (P < .001) and significantly worse event-free survivorship (P < .0001). These findings provide further insights into the genetic and biological basis of inherited genetic susceptibility to BCP-ALL and the influence of constitutional genotype on disease development.
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A genome-wide association study identifies multiple susceptibility loci for chronic lymphocytic leukemia.
Nat. Genet.
PUBLISHED: 08-20-2013
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Genome-wide association studies (GWAS) of chronic lymphocytic leukemia (CLL) have shown that common genetic variation contributes to the heritable risk of CLL. To identify additional CLL susceptibility loci, we conducted a GWAS and performed a meta-analysis with a published GWAS totaling 1,739 individuals with CLL (cases) and 5,199 controls with validation in an additional 1,144 cases and 3,151 controls. A combined analysis identified new susceptibility loci mapping to 3q26.2 (rs10936599, P = 1.74 × 10(-9)), 4q26 (rs6858698, P = 3.07 × 10(-9)), 6q25.2 (IPCEF1, rs2236256, P = 1.50 × 10(-10)) and 7q31.33 (POT1, rs17246404, P = 3.40 × 10(-8)). Additionally, we identified a promising association at 5p15.33 (CLPTM1L, rs31490, P = 1.72 × 10(-7)) and validated recently reported putative associations at 5p15.33 (TERT, rs10069690, P = 1.12 × 10(-10)) and 8q22.3 (rs2511714, P = 2.90 × 10(-9)). These findings provide further insights into the genetic and biological basis of inherited genetic susceptibility to CLL.
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Contribution of nitrated phenols to wood burning brown carbon light absorption in Detling, United Kingdom during winter time.
Environ. Sci. Technol.
PUBLISHED: 06-10-2013
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We show for the first time quantitative online measurements of five nitrated phenol (NP) compounds in ambient air (nitrophenol C6H5NO3, methylnitrophenol C7H7NO3, nitrocatechol C6H5NO4, methylnitrocatechol C7H7NO4, and dinitrophenol C6H4N2O5) measured with a micro-orifice volatilization impactor (MOVI) high-resolution chemical ionization mass spectrometer in Detling, United Kingdom during January-February, 2012. NPs absorb radiation in the near-ultraviolet (UV) range of the electromagnetic spectrum and thus are potential components of poorly characterized light-absorbing organic matter ("brown carbon") which can affect the climate and air quality. Total NP concentrations varied between less than 1 and 98 ng m(-3), with a mean value of 20 ng m(-3). We conclude that NPs measured in Detling have a significant contribution from biomass burning with an estimated emission factor of 0.2 ng (ppb CO)(-1). Particle light absorption measurements by a seven-wavelength aethalometer in the near-UV (370 nm) and literature values of molecular absorption cross sections are used to estimate the contribution of NP to wood burning brown carbon UV light absorption. We show that these five NPs are potentially important contributors to absorption at 370 nm measured by an aethalometer and account for 4 ± 2% of UV light absorption by brown carbon. They can thus affect atmospheric radiative transfer and photochemistry and with that climate and air quality.
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Media multitasking and failures of attention in everyday life.
Psychol Res
PUBLISHED: 06-04-2013
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Using a series of online self-report measures, we examine media multitasking, a particularly pervasive form of multitasking, and its relations to three aspects of everyday attention: (1) failures of attention and cognitive errors (2) mind wandering, and (3) attentional control with an emphasis on attentional switching and distractibility. We observed a positive correlation between levels of media multitasking and self-reports of attentional failures, as well as with reports of both spontaneous and deliberate mind wandering. No correlation was observed between media multitasking and self-reported memory failures, lending credence to the hypothesis that media multitasking may be specifically related to problems of inattention, rather than cognitive errors in general. Furthermore, media multitasking was not related with self-reports of difficulties in attention switching or distractibility. We offer a plausible causal structural model assessing both direct and indirect effects among media multitasking, attentional failures, mind wandering, and cognitive errors, with the heuristic goal of constraining and motivating theories of the effects of media multitasking on inattention.
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The influence of MRI scan position on patients with oropharyngeal cancer undergoing radical radiotherapy.
Radiat Oncol
PUBLISHED: 05-24-2013
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BACKGROUND: The purpose of this study was to demonstrate how magnetic resonance imaging (MRI) patient position protocols influence registration quality in patients with oropharyngeal cancer undergoing radical radiotherapy and the consequences for gross tumour volume (GTV) definition and radiotherapy planning.Methods and materials: Twenty-two oropharyngeal patients underwent a computed tomography (CT), a diagnostic MRI (MRID) and an MRI in the radiotherapy position within an immobilization mask (MRIRT). Clinicians delineated the GTV on the CT viewing the MRID separately (GTVC); on the CT registered to MRID (GTVD) and on the CT registered to MRIRT (GTVRT). Planning target volumes (PTVs) were denoted similarly. Registration quality was assessed by measuring disparity between structures in the three set-ups. Volumetric modulated arc therapy (VMAT) radiotherapy planning was performed for PTVC, PTVD and PTVRT. To determine the dose received by the reference PTVRT, we optimized for PTVC and PTVD while calculating the dose to PTVRT. Statistical significance was determined using the two-tailed Mann--Whitney or two-tailed paired student t-tests. RESULTS: A significant improvement in registration accuracy was found between CT and MRIRT versus the MRID measuring distances from the centre of structures (geometric mean error of 2.2 mm versus 6.6 mm). The mean GTVC (44.1 cm3) was significantly larger than GTVD (33.7 cm3, p value = 0.027) or GTVRT (30.5 cm3, p value = 0.014). When optimizing the VMAT plans for PTVC and investigating the mean dose to PTVRT neither the dose to 99% (58.8%) nor 95% of the PTV (84.7%) were found to meet the required clinical dose constraints of 90% and 95% respectively. Similarly, when optimizing for PTVD the mean dose to PTVRT did not meet clinical dose constraints for 99% (14.9%) nor 95% of the PTV (66.2%). Only by optimizing for PTVRT were all clinical dose constraints achieved. CONCLUSIONS: When oropharyngeal patients MRI scans are performed in the radiotherapy position there are significant improvements in CT-MR image registration, target definition and PTV dose coverage.
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A comparison of in vitro nucleosome positioning mapped with chicken, frog and a variety of yeast core histones.
J. Mol. Biol.
PUBLISHED: 04-25-2013
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Using high-throughput sequencing, we have mapped sequence-directed nucleosome positioning in vitro on four plasmid DNAs containing DNA fragments derived from the genomes of sheep, drosophila, human and yeast. Chromatins were prepared by reconstitution using chicken, frog and yeast core histones. We also assembled yeast chromatin in which histone H3 was replaced by the centromere-specific histone variant, Cse4. The positions occupied by recombinant frog and native chicken histones were found to be very similar. In contrast, nucleosomes containing the canonical yeast octamer or, in particular, the Cse4 octamer were assembled at distinct populations of locations, a property that was more apparent on particular genomic DNA fragments. The factors that may contribute to this variation in nucleosome positioning and the implications of the behavior are discussed.
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Performance reactivity in a continuous-performance task: implications for understanding post-error behavior.
Conscious Cogn
PUBLISHED: 03-29-2013
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Although there has been considerable interest in the effects of errors on subsequent performance, relatively few studies have considered the effects of non-error events that contain some performance-relevant information, such as correct performance on critical trials. In the present article, we propose and assess a hypothesis of performance reactivity. In support of this hypothesis, we provide evidence of performance decrements following both incorrect and correct responses but not following performance-irrelevant events. More specifically, in a continuous response task (Sustained Attention to Response Task), we (1) replicate previous findings that errors of commission on rare NOGO trials produce decrements in subsequent performance, and (2) observe that correct withholds to NOGO trials produce decrements in subsequent accuracy relative to task-irrelevant tones. These results corroborate a hypothesis that some error-related effects on subsequent performance are not unique, but are instead a particularly salient version of a more general performance-reactivity effect.
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Aetiology, genetics and prevention of secondary neoplasms in adult cancer survivors.
Nat Rev Clin Oncol
PUBLISHED: 03-26-2013
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Second and higher-order malignancies now comprise about 18% of all incident cancers in the USA, superseding first primary cancers of the breast, lung, and prostate. The occurrence of second malignant neoplasms (SMN) is influenced by a myriad of factors, including the late effects of cancer therapy, shared aetiological factors with the primary cancer (such as tobacco use, excessive alcohol intake, and obesity), genetic predisposition, environmental determinants, host effects, and combinations of factors, including gene-environment interactions. The influence of these factors on SMN in survivors of adult-onset cancer is reviewed here. We also discuss how modifiable behavioural and lifestyle factors may contribute to SMN, and how these factors can be managed. Cancer survivorship provides an opportune time for oncologists and other health-care providers to counsel patients with regard to health promotion, not only to reduce SMN risk, but to minimize co-morbidities. In particular, the importance of smoking cessation, weight control, physical activity, and other factors consonant with adoption of a healthy lifestyle should be consistently emphasized to cancer survivors. Clinicians can also play a critical role by endorsing genetic counselling for selected patients and making referrals to dieticians, exercise trainers, and others to assist with lifestyle change interventions.
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Common variation at 3q26.2, 6p21.33, 17p11.2 and 22q13.1 influences multiple myeloma risk.
Nat. Genet.
PUBLISHED: 03-06-2013
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To identify variants for multiple myeloma risk, we conducted a genome-wide association study with validation in additional series totaling 4,692 individuals with multiple myeloma (cases) and 10,990 controls. We identified four risk loci at 3q26.2 (rs10936599, P = 8.70 × 10(-14)), 6p21.33 (rs2285803, PSORS1C2, P = 9.67 × 10(-11)), 17p11.2 (rs4273077, TNFRSF13B, P = 7.67 × 10(-9)) and 22q13.1 (rs877529, CBX7, P = 7.63 × 10(-16)). These data provide further evidence for genetic susceptibility to this B-cell hematological malignancy, as well as insight into the biological basis of predisposition.
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Head drop syndrome secondary to multimodality treatments for head and neck cancer.
Laryngoscope
PUBLISHED: 02-12-2013
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Five patients under follow-up for head and neck squamous cell carcinoma (SCC) at Southern General Hospital Glasgow presented with a fixed flexion deformity of the neck. These cases are characterized by the onset of severe weakness and atrophy of the neck extensor muscles and anterior fibrosis forcing the mandible to the chest wall. This causes considerable morbidity with communication, feeding, and appearance. This is a rare complication with no curative treatments that has not been reported previously by a UK center and is likely to become important with the increased use of multimodality treatments for head and neck SCC.
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Belief bias during reasoning among religious believers and skeptics.
Psychon Bull Rev
PUBLISHED: 02-12-2013
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We provide evidence that religious skeptics, as compared to believers, are both more reflective and effective in logical reasoning tasks. While recent studies have reported a negative association between an analytic cognitive style and religiosity, they focused exclusively on accuracy, making it difficult to specify potential underlying cognitive mechanisms. The present study extends the previous research by assessing both performance and response times on quintessential logical reasoning problems (syllogisms). Those reporting more religious skepticism made fewer reasoning errors than did believers. This finding remained significant after controlling for general cognitive ability, time spent on the problems, and various demographic variables. Crucial for the purpose of exploring underlying mechanisms, response times indicated that skeptics also spent more time reasoning than did believers. This novel finding suggests a possible role of response slowing during analytic problem solving as a component of cognitive style that promotes overriding intuitive first impressions. Implications for using additional processing measures, such as response time, to investigate individual differences in cognitive style are discussed.
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Age differences in attention lapses mask age differences in memory failures: a methodological note on suppression.
Front Psychol
PUBLISHED: 02-11-2013
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Although objective measures of memory performance typically indicate memory declines with age, self-reported memory failures often show no relation to age. In contrast, self-reported attention failures are reliably negatively correlated with age. This contrast suggests the possibility that age-related awareness and reporting of memory failures might be masked by a concurrent decrease in attention failures, which would reduce encoding failures with age and hence reduce perceived memory failures. Self-reported problems of attention and memory were evaluated in two samples with the ages spanning eight decades. Initial analysis indicated that attention failures significantly decreased with age, whereas memory problems did not to differ across age. The association of self-reported memory failures became significantly positive, however, when residualized on attention lapses. In contrast, the correlation between attention lapses and age was modestly affected when memory failures were controlled. These results highlight the close relation of attention lapses and memory problems and, beyond the implications of individual differences in attention for memory research, suggest the advisability of assessing attention failures for a full evaluation of memory problems.
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Enhancing SART Validity by Statistically Controlling Speed-Accuracy Trade-Offs.
Front Psychol
PUBLISHED: 01-01-2013
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Numerous studies focused on elucidating the correlates, causes, and consequences of inattention/attention-lapses employ the Sustained Attention to Response Task (SART), a GO-NOGO task with infrequent withholds. Although the SART has become popular among inattention researchers, recent work has demonstrated its susceptibility to speed-accuracy trade-offs (SATOs), rendering its assessment of inattention problematic. Here, we propose and illustrate methods to statistically control for the occurrence of SATOs during SART performance. The statistical solutions presented here can be used to correct standard SART-error scores, including those of already-published data, thereby allowing researchers to re-examine existing data, and to more sensitively evaluate the validity of earlier conclusions.
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A functional variant in the core promoter of the CD95 cell death receptor gene predicts prognosis in acute promyelocytic leukemia.
Blood
PUBLISHED: 11-14-2011
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Up to 15% of acute promyelocytic leukemia (APL) patients fail to achieve or maintain remission. We investigated a common G > A polymorphism at position -1377 (rs2234767) in the core promoter of the CD95 cell death receptor gene in 708 subjects with acute myeloid leukemia, including 231 patients with APL. Compared with the GG genotype, carrier status for the -1377A variant was associated with a significantly worse prognosis in APL patients. Carriers were more likely to fail remission induction (odds ratio = 4.22; 95% confidence interval, 1.41-12.6, P = .01), were more likely to die during the first 8 weeks of remission induction therapy (hazard ratio = 7.26; 95% confidence interval, 2.39-22.9, P = .0005), and had a significantly worse 5-year overall survival (odds ratio = 2.14; 95% confidence interval, 1.10-4.15, P = .03). The -1377A variant destroys a binding site for the SP1 transcriptional regulator and is associated with lower transcriptional activity of the CD95 promoter. Identifying patients at high risk of life-threatening events, such as remission induction failure, is a high priority in APL, especially because such events represent a major cause of death despite the introduction of differentiation therapy.
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Consistency of sustained attention across modalities: comparing visual and auditory versions of the SART.
Can J Exp Psychol
PUBLISHED: 09-12-2011
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We develop and assess an auditory version of an increasingly widely used measure of sustained attention, the Sustained Attention to Response Task (SART). In two separate studies, the auditory SART generated slower response times and fewer errors than the visual SART. Proportion of errors, response times, and response time variability were, however, significantly and strongly correlated across the two modalities. The cross-modality correlations were generally equivalent to split-half correlations within modalities, indicating a strong agreement of the assessment of individual differences in sustained attention in the visual and auditory modalities. The foregoing results plus the finding that errors on the auditory SART were reduced suggests that the auditory SART may be a preferred alternative for use with populations with deficits in sustained attention.
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Challenge and error: critical events and attention-related errors.
Cognition
PUBLISHED: 07-11-2011
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Attention lapses resulting from reactivity to task challenges and their consequences constitute a pervasive factor affecting everyday performance errors and accidents. A bidirectional model of attention lapses (error?attention-lapse: Cheyne, Solman, Carriere, & Smilek, 2009) argues that errors beget errors by generating attention lapses; resource-depleting cognitions interfering with attention to subsequent task challenges. Attention lapses lead to errors, and errors themselves are a potent consequence often leading to further attention lapses potentially initiating a spiral into more serious errors. We investigated this challenge-induced error?attention-lapse model using the Sustained Attention to Response Task (SART), a GO-NOGO task requiring continuous attention and response to a number series and withholding of responses to a rare NOGO digit. We found response speed and increased commission errors following task challenges to be a function of temporal distance from, and prior performance on, previous NOGO trials. We conclude by comparing and contrasting the present theory and findings to those based on choice paradigms and argue that the present findings have implications for the generality of conflict monitoring and control models.
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Volume enhancement of upper lip in secondary cleft deformity using composite mastoid tissue.
Aesthetic Plast Surg
PUBLISHED: 07-07-2011
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Secondary cleft lip deformity correction needs thorough assessment and planning to optimize treatment and achieve good results. Deficient volume of the upper lip, which is one of the most common secondary cleft lip deformities, has been addressed in many ways using tissues from local or distant areas. Consideration must be given to safety, easy availability of the tissues, minimum morbidity, and longevity of the results when selecting a procedure.
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Attention failures versus misplaced diligence: separating attention lapses from speed-accuracy trade-offs.
Conscious Cogn
PUBLISHED: 06-16-2011
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In two studies of a GO-NOGO task assessing sustained attention, we examined the effects of (1) altering speed-accuracy trade-offs through instructions (emphasizing both speed and accuracy or accuracy only) and (2) auditory alerts distributed throughout the task. Instructions emphasizing accuracy reduced errors and changed the distribution of GO trial RTs. Additionally, correlations between errors and increasing RTs produced a U-function; excessively fast and slow RTs accounted for much of the variance of errors. Contrary to previous reports, alerts increased errors and RT variability. The results suggest that (1) standard instructions for sustained attention tasks, emphasizing speed and accuracy equally, produce errors arising from attempts to conform to the misleading requirement for speed, which become conflated with attention-lapse produced errors and (2) auditory alerts have complex, and sometimes deleterious, effects on attention. We argue that instructions emphasizing accuracy provide a more precise assessment of attention lapses in sustained attention tasks.
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Host alloreactive memory T cells influence tolerance to kidney allografts in nonhuman primates.
Sci Transl Med
PUBLISHED: 06-10-2011
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Transplant tolerance, defined as indefinite allograft survival without immunosuppression, has been regularly achieved in laboratory mice but not in nonhuman primates or humans. In contrast to laboratory mice, primates regularly have high frequencies of alloreactive memory T cells (TMEMs) before transplantation. These TMEMs are poorly sensitive to conventional immunosuppression and costimulation blockade, and the presence of donor-reactive TMEMs in primates may account for their resistance to transplant tolerance protocols that have proven consistently effective in mice. We measured the frequencies of anti-donor TMEMs before and after transplantation in a series of rejecting and tolerant monkeys that underwent nonmyeloablative conditioning, short-term immunosuppression, and combined allogeneic kidney/cell transplantation. Transplants were acutely rejected in all the monkeys with high numbers of donor-specific TMEMs before transplantation. In contrast, long-term survival was observed in the recipients harboring lower frequencies of anti-donor TMEMs before transplantation. Similar amounts of TMEM homeostatic expansion were recorded in all transplanted monkeys upon hematopoietic reconstitution; however, only the tolerant monkeys had no expansion or activation of donor-reactive TMEMs after transplantation. These results indicate that the presence of high frequencies of host donor-reactive TMEMs before transplantation impairs tolerance induction to kidney allografts in this nonhuman primate model. Indeed, recipients harboring a low anamnestic reactivity to their donor before transplantation were successfully rendered tolerant via infusion of donor cells and short-term immunosuppression. This suggests that selection of allogeneic donors with low memory responses in recipients may be essential to successful transplant tolerance induction in patients.
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Autoimmune sensitization to cardiac myosin leads to acute rejection of cardiac allografts in miniature swine.
Transplantation
PUBLISHED: 04-23-2011
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Recent studies in mice and patients suggest that posttransplantation induction of autoimmune responses to tissue-specific antigens contributes to the rejection of major histocompatibility complex mismatched allotransplants. The relevance of this phenomenon to the rejection of major and minor histocompatibility-mismatched allografts performed in large-animal models remains to be established.
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Absence of Gal epitope prolongs survival of swine lungs in an ex vivo model of hyperacute rejection.
Xenotransplantation
PUBLISHED: 04-19-2011
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Galactosyl transferase gene knock-out (GalTKO) swine offer a unique tool to evaluate the role of the Gal antigen in xenogenic lung hyperacute rejection.
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MHC variation and risk of childhood B-cell precursor acute lymphoblastic leukemia.
Blood
PUBLISHED: 11-08-2010
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A role for specific human leukocyte antigen (HLA) variants in the etiology of childhood acute lymphoblastic leukemia (ALL) has been extensively studied over the last 30 years, but no unambiguous association has been identified. To comprehensively study the relationship between genetic variation within the 4.5 Mb major histocompatibility complex genomic region and precursor B-cell (BCP) ALL risk, we analyzed 1075 observed and 8176 imputed single nucleotide polymorphisms and their related haplotypes in 824 BCP-ALL cases and 4737 controls. Using these genotypes we also imputed both common and rare alleles at class I (HLA-A, HLA-B, and HLA-C) and class II (HLA-DRB1, HLA-DQA1, and HLA-DQB1) HLA loci. Overall, we found no statistically significant association between variants and BCP-ALL risk. We conclude that major histocompatibility complex-defined variation in immune-mediated response is unlikely to be a major risk factor for BCP-ALL.
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Testicular cancer survivorship: research strategies and recommendations.
J. Natl. Cancer Inst.
PUBLISHED: 06-28-2010
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Testicular cancer represents the most curable solid tumor, with a 10-year survival rate of more than 95%. Given the young average age at diagnosis, it is estimated that effective treatment approaches, in particular, platinum-based chemotherapy, have resulted in an average gain of several decades of life. This success, however, is offset by the emergence of considerable long-term morbidity, including second malignant neoplasms, cardiovascular disease, neurotoxicity, nephrotoxicity, pulmonary toxicity, hypogonadism, decreased fertility, and psychosocial problems. Data on underlying genetic or molecular factors that might identify those patients at highest risk for late sequelae are sparse. Genome-wide association studies and other translational molecular approaches now provide opportunities to identify testicular cancer survivors at greatest risk for therapy-related complications to develop evidence-based long-term follow-up guidelines and interventional strategies. We review research priorities identified during an international workshop devoted to testicular cancer survivors. Recommendations include 1) institution of lifelong follow-up of testicular cancer survivors within a large cohort setting to ascertain risks of emerging toxicities and the evolution of known late sequelae, 2) development of comprehensive risk prediction models that include treatment factors and genetic modifiers of late sequelae, 3) elucidation of the effect(s) of decades-long exposure to low serum levels of platinum, 4) assessment of the overall burden of medical and psychosocial morbidity, and 5) the eventual formulation of evidence-based long-term follow-up guidelines and interventions. Just as testicular cancer once served as the paradigm of a curable malignancy, comprehensive follow-up studies of testicular cancer survivors can pioneer new methodologies in survivorship research for all adult-onset cancer.
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Conjugate vaccines for enteric fever: proceedings of a meeting organized in New Delhi, India in 2009.
J Infect Dev Ctries
PUBLISHED: 03-24-2010
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Enteric fever is responsible for significant morbidity in South Asia and high prevalence of severe disease is seen in children under two years of age. Effective typhoid vaccines are available, but they cannot be used for children under two years of age and also have some limitations in older age groups. Participants supported development of a Salmonella Typhi conjugate vaccine able to induce effective, long-lasting immunity in young children. The role of Salmonella Paratyphi A as a cause of enteric fever was discussed and consensus reached that a bivalent S. Typhi-S. Paratyphi A conjugate vaccine is highly desirable; however, considering disease epidemiology and the advanced status of vaccine development, rapid introduction of monovalent S. Typhi conjugate vaccine into vaccination programs of South Asia was recommended. Prevention should be emphasized, available vaccines used, and efforts toward improving sanitation continued. Success of the new vaccine will depend on several factors, including delivery costs and governmental ability to adopt and implement suitable immunization programs. To ensure good immunization coverage, the conjugate vaccine could be administered either to young infants, concomitantly with infant EPI vaccines, or to older infants, concomitantly with measles vaccine, currently given at 9 to 12 months. The need for new combination vaccines, containing both EPI and typhoid antigens, was discussed as a tool to increase coverage and reduce the number of injections and priority conflicts in a crowded infant vaccination schedule. However, stand-alone enteric fever conjugate vaccines would allow more flexibility to immunize different age groups and therefore should be rapidly developed.
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Genome-wide homozygosity signatures and childhood acute lymphoblastic leukemia risk.
Blood
PUBLISHED: 03-15-2010
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Recent studies have reported that regions of homozygosity (ROH) in the genome are detectable in outbred populations and can be associated with an increased risk of malignancy. To examine whether homozygosity is associated with an increased risk of developing childhood B-cell precursor acute lymphoblastic leukemia (BCP-ALL), we analyzed 824 ALL cases and 2398 controls genotyped for 292 200 tagging SNPs. Across the genome, cumulative distribution of ROH was not significantly different between cases and controls. Four common ROH at 10p11.2-10q11.21, 1p31.1, 19p13.2-3, and 20q11.1-23 were, however, associated with ALL risk at P less than .01 (including 1 ROH to which the erythropoietin receptor [EPOR] gene maps, P = .005) but were nonsignificant after adjusting for multiple testing. Our findings make it unlikely that levels of measured homozygosity, caused by autozygosity, uniparental isodisomy, or hemizygosity, play a major role in defining BCP-ALL risk in predominantly outbred populations.
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Incidence and risk factors of persistent air leak after major pulmonary resection and use of chemical pleurodesis.
Ann. Thorac. Surg.
PUBLISHED: 02-23-2010
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Persistent air leak (PAL; defined as air leak > 5 days) after major pulmonary resection is prevalent and associated with significant morbidity. This study examines an incompletely characterized treatment for the management of PAL, chemical pleurodesis.
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Non-homologous end-joining gene profiling reveals distinct expression patterns associated with lymphoma and multiple myeloma.
Br. J. Haematol.
PUBLISHED: 02-08-2010
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Repair of DNA strand breaks induced during lymphoid antigen receptor rearrangement involves non-homologous end-joining (NHEJ). We investigated NHEJ in the aetiology of lymphoproliferative disorders (LPDs) and the disease subtypes therein through real-time quantitative RT-PCR gene expression analysis. Lower expression of XRCC6 and MRE11A was observed in all tumours, with higher expression of both XRCC4 and RAD50 observed only in multiple myeloma (MM). Hierarchical clustering enabled tumours to be clearly distinguished from controls, and by morphological sub-type. We postulate this identifies targets worthy of investigation in the genetic predisposition, pathogenesis and prognosis of lymphoid malignancies.
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Variation in CDKN2A at 9p21.3 influences childhood acute lymphoblastic leukemia risk.
Nat. Genet.
PUBLISHED: 01-25-2010
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Using data from a genome-wide association study of 907 individuals with childhood acute lymphoblastic leukemia (cases) and 2,398 controls and with validation in samples totaling 2,386 cases and 2,419 controls, we have shown that common variation at 9p21.3 (rs3731217, intron 1 of CDKN2A) influences acute lymphoblastic leukemia risk (odds ratio = 0.71, P = 3.01 x 10(-11)), irrespective of cell lineage.
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Genetic variation in the folate metabolic pathway and risk of childhood leukemia.
Blood
PUBLISHED: 01-25-2010
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Studies of childhood leukemia and the potential etiologic role of genetic variation in folate metabolism have produced conflicting findings and have often been based on small numbers. We investigated the association between polymorphisms in key folate metabolism enzymes (MTHFR 677 C>T, MTHFR 1298 A>C, SHMT1 1420 C>T, MTR 2756 A>G, TS 1494del6, and TS 28bp repeat) in 939 cases of childhood acute lymphoblastic leukemia (ALL) and 89 cases of acute myeloid leukemia (AML) recruited into the United Kingdom Childhood Cancer Study. We also examined the maternal genotypes of 752 of these cases. Data from 824 noncancer controls recruited were used for comparison. No evidence of an association with MTHFR 677 was observed for ALL or AML, either in children or their mothers. However, in children an increased risk of ALL (odds ratio [OR] = 1.88; 95% confidence interval [CI], 1.16-3.07; P = .010) and AML (OR = 2.74; 95% CI, 1.07-7.01; P = .036) was observed with the MTR 2756 GG genotype; the association was most pronounced for cases with the MLL translocation (OR = 4.90; 95% CI, 1.30-18.45; P = .019). These data suggest that genetic variation in methionine synthase could mediate risk of childhood leukemia, either via effects on DNA methylation or via effects on fetal growth and development.
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Common variants at 2q37.3, 8q24.21, 15q21.3 and 16q24.1 influence chronic lymphocytic leukemia risk.
Nat. Genet.
PUBLISHED: 01-10-2010
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To identify new risk variants for chronic lymphocytic leukemia (CLL), we conducted a genome-wide association study of 299,983 tagging SNPs, with validation in four additional series totaling 2,503 cases and 5,789 controls. We identified four new risk loci for CLL at 2q37.3 (rs757978, FARP2; odds ratio (OR) = 1.39; P = 2.11 x 10(-9)), 8q24.21 (rs2456449; OR = 1.26; P = 7.84 x 10(-10)), 15q21.3 (rs7169431; OR = 1.36; P = 4.74 x 10(-7)) and 16q24.1 (rs305061; OR = 1.22; P = 3.60 x 10(-7)). We also found evidence for risk loci at 15q25.2 (rs783540, CPEB1; OR = 1.18; P = 3.67 x 10(-6)) and 18q21.1 (rs1036935; OR = 1.22; P = 2.28 x 10(-6)). These data provide further evidence for genetic susceptibility to this B-cell hematological malignancy.
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Melanocortin 1 receptor (MC1R), pigmentary characteristics and sun exposure: findings from a case-control study of diffuse large B-cell and follicular lymphoma.
Cancer Epidemiol
PUBLISHED: 01-07-2010
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The relationship between skin cancer and non-Hodgkin lymphoma (NHL) suggests common genetic, host or environmental causes. Ultraviolet radiation (UVR), pigmentary characteristics have been linked with both malignancies, and for skin cancer, the melanocortin 1 receptor (MC1R) which influences pigmentation has also been implicated. This paper reports on the relationship between MC1R, skin, hair and eye colour, time spent outdoors, and diffuse large B-cell lymphoma (DLBCL) and follicular lymphoma (FL). Persons carrying MC1R homozygote variant alleles at R151C, R160W, D294H and D84E were more likely to have fair skin, red hair and to spend less time outdoors than those who did not. The variant allele at V92M was associated with FL (odds ratio (OR)=1.61, 95% confidence interval (CI) 1.08-2.39) and the r:wild type genotype with DLBCL (OR=0.58, 95% CI 0.38-0.89). Interactions between MC1R genotypes and skin colour influenced DLBCL risk; the RR genotype increased risk in individuals with medium or dark skin, based on 5 cases and no controls, but decreased risk among those of fair skin. On the whole, DLBCL and FL risk were not related to genetic variation in MC1R, pigmentation or time spent outdoors.
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Activity-dependent gene transcription as a long-term influence on receptor signalling.
Biochem. Soc. Trans.
PUBLISHED: 11-14-2009
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The regulation of synaptic glutamate receptor and GABA(A)R (gamma-aminobutyric acid subtype A receptor) levels is a key component of synaptic plasticity. Most forms of neuronal plasticity are associated with the induction of the transcription factor zif268 (egr1). Hence, it is predicted that zif268 may regulate transcription of genes associated with glutamate receptors and/or GABA(A)Rs. It turns out that receptor regulation by zif268 tends to be indirect. Induction of zif268 in neurons leads to altered expression of proteasome subunit and proteasome-regulatory genes, thereby changing the capacity of the neuron to degrade synaptic proteins, including receptors and receptor subunits. In addition, zif268 alters the transcription of genes associated with GABA(A)R expression and trafficking, such as ubiquilin and gephyrin. This indirect regulation of receptor turnover is likely to contribute to the delayed, but long-lasting, phases of synaptic plasticity and also to the synaptic dysfunction associated with diseases such as schizophrenia and Alzheimers disease, where zif268 expression is reduced.
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Association of molecular markers with toxicity outcomes in a randomized trial of chemotherapy for advanced colorectal cancer: the FOCUS trial.
J. Clin. Oncol.
PUBLISHED: 10-26-2009
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Predicting efficacy and toxicity could potentially allow individualization of cancer therapy. We investigated putative pharmacogenetic markers of chemotherapy toxicity in a large randomized trial. Patients, Materials, and
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Development of a species-specific coproantigen ELISA for human Taenia solium taeniasis.
Am. J. Trop. Med. Hyg.
PUBLISHED: 08-27-2009
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Taenia solium causes human neurocysticercosis and is endemic in underdeveloped countries where backyard pig keeping is common. Microscopic fecal diagnostic methods for human T. solium taeniasis are not very sensitive, and Taenia saginata and Taenia solium eggs are indistinguishable under the light microscope. Coproantigen (CoAg) ELISA methods are very sensitive, but currently only genus (Taenia) specific. This paper describes the development of a highly species-specific coproantigen ELISA test to detect T. solium intestinal taeniasis. Sensitivity was maintained using a capture antibody of rabbit IgG against T. solium adult whole worm somatic extract, whereas species specificity was achieved by utilization of an enzyme-conjugated rabbit IgG against T. solium adult excretory-secretory (ES) antigen. A known panel of positive and negative human fecal samples was tested with this hybrid sandwich ELISA. The ELISA test gave 100% specificity and 96.4% sensitivity for T. solium tapeworm carriers (N = 28), with a J index of 0.96. This simple ELISA incorporating anti-adult somatic and anti-adult ES antibodies provides the first potentially species-specific coproantigen test for human T. solium taeniasis.
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POINT: Operative risk of pneumonectomy--influence of preoperative induction therapy.
J. Thorac. Cardiovasc. Surg.
PUBLISHED: 07-22-2009
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Prior data indicate increased perioperative morbidity and mortality in patients receiving induction chemoradiotherapy before pneumonectomy for lung cancer.
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Polymorphisms in the nucleotide excision repair gene ERCC2/XPD and risk of non-Hodgkin lymphoma.
Cancer Epidemiol
PUBLISHED: 06-10-2009
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Non-Hodgkin lymphoma (NHL) represents a complex group of B- and T-cell malignancies characterised by chromosomal translocations. Since defects in DNA repair result in an increased frequency of chromosomal aberrations it has been hypothesised that genetic variation in DNA repair may be associated with risk of NHL. To investigate the relationship between DNA repair and NHL we analysed polymorphisms in XPD (R156R, D312N, K751Q) using DNA collected in a UK population-based case-control study of lymphoma. We observed no association between genetic variation in XPD and risk of NHL. However, the XPD 751 Gln allele was associated with a two-fold decreased risk of diffuse large B-cell lymphoma (OR 0.56, 95% CI 0.34-0.92, p=0.02), the major subtype of NHL. Overall, our study identifies that XPD polymorphisms may be important in the aetiology of NHL although analysis of additional polymorphisms and extended haplotype studies are required to clarify their role.
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Loci on 7p12.2, 10q21.2 and 14q11.2 are associated with risk of childhood acute lymphoblastic leukemia.
Nat. Genet.
PUBLISHED: 04-08-2009
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To identify risk variants for childhood acute lymphoblastic leukemia (ALL), we conducted a genome-wide association study of two case-control series, analyzing the genotypes with respect to 291,423 tagging SNPs in a total of 907 ALL cases and 2,398 controls. We identified risk loci for ALL at 7p12.2 (IKZF1, rs4132601, odds ratio (OR) = 1.69, P = 1.20 x 10(-19)), 10q21.2 (ARID5B, rs7089424, OR = 1.65, P = 6.69 x 10(-19)) and 14q11.2 (CEBPE, rs2239633, OR = 1.34, P = 2.88 x 10(-7)). The 10q21.2 (ARID5B) risk association appears to be selective for the subset of B-cell precursor ALL with hyperdiploidy. These data show that common low-penetrance susceptibility alleles contribute to the risk of developing childhood ALL and provide new insight into disease causation of this specific hematological cancer. Notably, all three risk variants map to genes involved in transcriptional regulation and differentiation of B-cell progenitors.
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Gender, socioeconomic status, need or access? Differences in statin prescribing across urban, rural and remote Australia.
Aust J Rural Health
PUBLISHED: 04-02-2009
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To assess differences in statin prescribing across Australia by geographic area.
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Caricature and contrast in the Upper Palaeolithic: morphometric evidence from cave art.
Perception
PUBLISHED: 03-28-2009
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The earliest known explicit and unambiguous employment of representation in external media is in the form of figurative depictions of large mammals during the Upper Palaeolithic. These images, though often created with evident technical skill and intimate knowledge of the subject matter, are frequently characterised by curious and pronounced distortions. We provide evidence, based on quantitative analysis of parietal graphic images of two commonly depicted species, for the hypothesis that certain of these distortions are neither errors nor idiosyncratic variations, but systematic deviations from veridicality in the form of caricatures consistent with cognitive principles of graded typicality and contrast in categorisation. Our analysis provides evidence that the first apparent conventions of representational art by humans were informed by basic cognitive-perceptual principles of categorisation.
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Genome-wide association study to identify novel loci associated with therapy-related myeloid leukemia susceptibility.
Blood
PUBLISHED: 03-18-2009
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Therapy-related acute myeloid leukemia (t-AML) is a rare but fatal complication of cytotoxic therapy. Whereas sporadic cancer results from interactions between complex exposures and low-penetrance alleles, t-AML results from an acute exposure to a limited number of potent genotoxins. Consequently, we hypothesized that the effect sizes of variants associated with t-AML would be greater than in sporadic cancer, and, therefore, that these variants could be detected even in a modest-sized cohort. To test this, we undertook an association study in 80 cases and 150 controls using Affymetrix Mapping 10K arrays. Even at nominal significance thresholds, we found a significant excess of associations over chance; for example, although 6 associations were expected at P less than .001, we found 15 (P(enrich) = .002). To replicate our findings, we genotyped the 10 most significantly associated single nucleotide polymorphisms (SNPs) in an independent t-AML cohort (n = 70) and obtained evidence of association with t-AML for 3 SNPs in the subset of patients with loss of chromosomes 5 or 7 or both, acquired abnormalities associated with prior exposure to alkylator chemotherapy. Thus, we conclude that the effect of genetic factors contributing to cancer risk is potentiated and more readily discernable in t-AML compared with sporadic cancer.
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Immunosuppression for lung transplantation.
Front Biosci (Landmark Ed)
PUBLISHED: 03-11-2009
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As a result of advances in surgical techniques, immunosuppressive therapy, and postoperative management, lung transplantation has become an established therapeutic option for individuals with a variety of end-stage lung diseases. The current 1-year actuarial survival rate following lung transplantation is approaching 80%. However, the 5- year actuarial survival rate has remained virtually unchanged at approximately 50% over the last 15 years due to the processes of acute and chronic lung allograft rejection (1). Clinicians still rely on a vast array of immunosuppressive agents to suppress the process of graft rejection, but find themselves limited by an inescapable therapeutic paradox. Insufficient immunosuppression results in graft loss due to rejection, while excess immunosuppression results in increased morbidity and mortality from opportunistic infections and malignancies. Indeed, graft rejection, infection, and malignancy are the three principal causes of mortality for the lung transplant recipient. One should also keep in mind that graft loss in a lung transplant recipient is usually a fatal event, since there is no practical means of long-term mechanical support, and since the prospects of re-transplantation are low, given the shortage of acceptable donor grafts. This chapter reviews the current state of immunosuppressive therapy for lung transplantation and suggests alternative paradigms for the management of future lung transplant recipients.
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High-frequency chest-wall compression during the 48 hours following thoracic surgery.
Respir Care
PUBLISHED: 02-28-2009
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Postoperative pneumonia continues to be a leading cause of mortality and morbidity after thoracic surgery. High-frequency chest-wall compression (HFCWC) is an established therapeutic adjunct for patients with chronic pulmonary disorders that impair bronchopulmonary secretion clearance. We studied the feasibility of applying HFCWC following thoracic surgery.
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High-resolution mapping of sequence-directed nucleosome positioning on genomic DNA.
J. Mol. Biol.
PUBLISHED: 02-10-2009
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We have mapped in vitro nucleosome positioning on the sheep beta-lactoglobulin gene using high-throughput sequencing to characterise the DNA sequences recovered from reconstituted nucleosomes. This methodology surpasses previous approaches for coverage, accuracy and resolution and, most importantly, offers a simple yet rapid and relatively inexpensive method to characterise genomic DNA sequences in terms of nucleosome positioning capacity. We demonstrate an unambiguous correspondence between in vitro and in vivo nucleosome positioning around the promoter of the gene; identify discrete, sequence-specific nucleosomal structures above the level of the canonical core particle-a feature that has implications for regulatory protein access and higher-order chromatin packing; and reveal new insights into the involvement of periodically organised dinucleotide sequence motifs of the type GG and CC and not AA and TT, as determinants of nucleosome positioning-an observation that supports the idea that the core histone octamer can exploit different patterns of sequence organisation, or structural potential, in the DNA to bring about nucleosome positioning.
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Does patient satisfaction of general practice change over a decade?
BMC Fam Pract
PUBLISHED: 02-08-2009
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The Patient Participation Program (PPP) was a patient satisfaction survey endorsed by the Royal Australian College of General Practitioners and designed to assist general practitioners in continuous quality improvement (CQI). The survey was been undertaken by 3500 practices and over a million patients between 1994 and 2003. This study aimed to use pooled patient questionnaire data to investigate changes in satisfaction with primary care over time.
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Absent minds and absent agents: attention-lapse induced alienation of agency.
Conscious Cogn
PUBLISHED: 01-29-2009
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We report a novel task designed to elicit transient attention-lapse induced alienation (ALIA) of agency experiences in normal participants. When attention-related action slips occur during the task, participants reported substantially decreased self control as well as a high degree of perceived agency attributed to the errant hand. In addition, participants reported being surprised by, and annoyed with, the actions of the errant hand. We argue that ALIA experiences occur because of constraints imposed by the close and precise temporal relations between intention formation and a contrary action employed in this paradigm. We note similarities between ALIA experiences and anarchic hand sign (AHS) and argue that, despite important differences, both ALIA experiences and AHS phenomenology reflect failures of executive control to intervene and cancel contrary affordance-driven habitual motor plans.
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Review of superior vena cava resection in the management of benign disease and pulmonary or mediastinal malignancies.
Ann. Thorac. Surg.
PUBLISHED: 01-25-2009
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Obstruction of the superior vena cava (SVC) by tumor or benign disease implies unreconstructable disease and poor outcome. We analyzed the operative results, graft patency, and survival in patients undergoing SVC resection and reconstruction for benign disease and pulmonary or mediastinal malignancy.
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Long-term results of sleeve lobectomy in the management of non-small cell lung carcinoma and low-grade neoplasms.
Ann. Thorac. Surg.
PUBLISHED: 01-21-2009
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The objective of this study was to evaluate the operative mortality, morbidity, and long-term survival of sleeve lobectomy for non-small cell lung cancer and low-grade neoplasms. We evaluated the effects of neoadjuvant therapy on the bronchial anastomotic complication rate and determined whether sleeve lobectomy performed in patients with N1 disease resulted in decreased overall survival.
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Wandering minds and wavering rhythms: linking mind wandering and behavioral variability.
J Exp Psychol Hum Percept Perform
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Mind wandering is a pervasive feature of human cognition often associated with the withdrawal of task-related executive control processes. Here, we explore the possibility that, in tasks requiring executive control to sustain consistent responding, moments of mind wandering could be associated with moments of increased behavioral variability. To test this possibility, we developed and administered a novel task (the metronome response task) in which participants were instructed to respond synchronously (via button presses) with the continuous rhythmic presentation of tones. We provide evidence (replicated across 2 independent samples) that response variability during the 5 trials preceding probe-caught reports of mind wandering (tuned-out and zoned-out mind wandering) is significantly greater than during the 5 trials preceding reports of on-task performance. These results suggest that, at least in some tasks, behavioral variability is an online marker of mind wandering.
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Characterizing the aging of biomass burning organic aerosol by use of mixing ratios: a meta-analysis of four regions.
Environ. Sci. Technol.
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Characteristic organic aerosol (OA) emission ratios (ERs) and normalized excess mixing ratios (NEMRs) for biomass burning (BB) events have been calculated from ambient measurements recorded during four field campaigns. Normalized OA mass concentrations measured using Aerodyne Research Inc. quadrupole aerosol mass spectrometers (Q-AMS) reveal a systematic variation in average values between different geographical regions. For each region, a consistent, characteristic ratio is seemingly established when measurements are collated from plumes of all ages and origins. However, there is evidence of strong regional and local-scale variability between separate measurement periods throughout the tropical, subtropical, and boreal environments studied. ERs close to source typically exceed NEMRs in the far-field, despite apparent compositional change and increasing oxidation with age. The absence of any significant downwind mass enhancement suggests no regional net source of secondary organic aerosol (SOA) from atmospheric aging of BB sources, in contrast with the substantial levels of net SOA formation associated with urban sources. A consistent trend of moderately reduced ?OA/?CO ratios with aging indicates a small net loss of OA, likely as a result of the evaporation of organic material from initial fire emissions. Variability in ERs close to source is shown to substantially exceed the magnitude of any changes between fresh and aged OA, emphasizing the importance of fuel and combustion conditions in determining OA loadings from biomass burning.
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Prevention of biofilm-induced capsular contracture with antibiotic-impregnated mesh in a porcine model.
Aesthet Surg J
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A growing body of evidence implicates subclinical (biofilm) infection around breast implants as an important cause of capsular contracture (CC).
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Impact of alternative fuels on emissions characteristics of a gas turbine engine - part 2: volatile and semivolatile particulate matter emissions.
Environ. Sci. Technol.
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The work characterizes the changes in volatile and semivolatile PM emissions from a gas turbine engine resulting from burning alternative fuels, specifically gas-to-liquid (GTL), coal-to-liquid (CTL), a blend of Jet A-1 and GTL, biodiesel, and diesel, to the standard Jet A-1. The data presented here, compares the mass spectral fingerprints of the different fuels as measured by the Aerodyne high resolution time-of-flight aerosol mass spectrometer. There were three sample points, two at the exhaust exit plane with dilution added at different locations and another probe located 10 m downstream. For emissions measured at the downstream probe when the engine was operating at high power, all fuels produced chemically similar organic PM, dominated by C(x)H(y) fragments, suggesting the presence of long chain alkanes. The second largest contribution came from C(x)H(y)O(z) fragments, possibly from carbonyls or alcohols. For the nondiesel fuels, the highest loadings of organic PM were from the downstream probe at high power. Conversely, the diesel based fuels produced more organic material at low power from one of the exit plane probes. Differences in the composition of the PM for certain fuels were observed as the engine power decreased to idle and the measurements were made closer to the exit plane.
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Thermoplasticity in the plant circadian clock: how plants tell the time-perature.
Plant Signal Behav
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In the March 2012 issue of The Plant Cell we describe extensive alternative splicing (AS) of Arabidopsis circadian clock genes. Notably these distinct post-transcriptional events associate with different steady-state temperatures and also with plants undergoing temperature transitions leading us to propose that temperature-associated AS is an additional mechanism involved in the operation and control of the plant circadian clock. Here we show that temperature associated AS also extends to REVEILLE 8 (RVE8), demonstrating a hitherto unrecognized link between the expression of this clock associated gene and temperature. Finally we discuss our observations of the plastic nature of clock gene expression at the post-transcriptional level in the context of the ongoing fascination of how plants respond to temperature.
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Improving attendance for cardiovascular risk assessment in Australian general practice: an RCT of a monetary incentive for patients.
BMC Fam Pract
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Preventive health care is an important part of general practice however uptake of activities by patients is variable. Monetary incentives for doctors have been used in the UK and Australia to improve rates of screening and immunisation. Few studies have focussed on incentives for patients to attend preventive health care examinations. Our objective was to investigate the use of a monetary incentive to increase patient attendance with their general practitioner for a cardiovascular risk assessment (CVRA).
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Analytic cognitive style predicts religious and paranormal belief.
Cognition
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An analytic cognitive style denotes a propensity to set aside highly salient intuitions when engaging in problem solving. We assess the hypothesis that an analytic cognitive style is associated with a history of questioning, altering, and rejecting (i.e., unbelieving) supernatural claims, both religious and paranormal. In two studies, we examined associations of God beliefs, religious engagement (attendance at religious services, praying, etc.), conventional religious beliefs (heaven, miracles, etc.) and paranormal beliefs (extrasensory perception, levitation, etc.) with performance measures of cognitive ability and analytic cognitive style. An analytic cognitive style negatively predicted both religious and paranormal beliefs when controlling for cognitive ability as well as religious engagement, sex, age, political ideology, and education. Participants more willing to engage in analytic reasoning were less likely to endorse supernatural beliefs. Further, an association between analytic cognitive style and religious engagement was mediated by religious beliefs, suggesting that an analytic cognitive style negatively affects religious engagement via lower acceptance of conventional religious beliefs. Results for types of God belief indicate that the association between an analytic cognitive style and God beliefs is more nuanced than mere acceptance and rejection, but also includes adopting less conventional God beliefs, such as Pantheism or Deism. Our data are consistent with the idea that two people who share the same cognitive ability, education, political ideology, sex, age and level of religious engagement can acquire very different sets of beliefs about the world if they differ in their propensity to think analytically.
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Alternative splicing mediates responses of the Arabidopsis circadian clock to temperature changes.
Plant Cell
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Alternative splicing plays crucial roles by influencing the diversity of the transcriptome and proteome and regulating protein structure/function and gene expression. It is widespread in plants, and alteration of the levels of splicing factors leads to a wide variety of growth and developmental phenotypes. The circadian clock is a complex piece of cellular machinery that can regulate physiology and behavior to anticipate predictable environmental changes on a revolving planet. We have performed a system-wide analysis of alternative splicing in clock components in Arabidopsis thaliana plants acclimated to different steady state temperatures or undergoing temperature transitions. This revealed extensive alternative splicing in clock genes and dynamic changes in alternatively spliced transcripts. Several of these changes, notably those affecting the circadian clock genes late elongated hypocotyl (LHY) and pseudo response regulator7, are temperature-dependent and contribute markedly to functionally important changes in clock gene expression in temperature transitions by producing nonfunctional transcripts and/or inducing nonsense-mediated decay. Temperature effects on alternative splicing contribute to a decline in LHY transcript abundance on cooling, but LHY promoter strength is not affected. We propose that temperature-associated alternative splicing is an additional mechanism involved in the operation and regulation of the plant circadian clock.
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Quantitative comparison of volumetric modulated arc therapy and intensity modulated radiotherapy plan quality in sino-nasal cancer.
J Med Phys
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The aim of this study was to compare various dosimetric parameters of dynamic mlc intensity modulated radiotherapy (IMRT) plans with volumetric modulated arc therapy (VMAT) plans for sino-nasal cancers, which are rare and complex tumors to treat with radiotherapy. IMRT using five fields, coplanar in the sagittal plane and VMAT employing two coplanar arc plans were created for five patients. The plans were assessed by comparing Conformity Index and Sigma Index (dose homogeneity) in the Planning Target Volume (PTV) and through comparison of dose-volume characteristics to the following organs at risk (OARs): Spinal cord, brainstem, eye, ipsilateral and contralateral optic nerve and the volume of brain receiving 10% of the prescribed dose (V(10%)). The total monitor units required to deliver the plan were also compared. Conformity Index was found to be superior in VMAT plans for three patients and in IMRT plans for two patients. Dose homogeneity within the PTV was better with VMAT plans for all five cases. The mean difference in Sigma Index was 0.68%. There was no significant difference in dose between IMRT and VMAT plans for any of the OARs assessed in these patients. The monitor units were significantly reduced in the VMAT plan in comparison to the IMRT plan for four out of five patients, with mean reduction of 66%. It was found in this study that for the treatment of sino-nasal cancer, VMAT produced minimal, and statistically insignificant improvement in dose homogeneity within the PTV when compared with IMRT. VMAT plans were delivered using significantly fewer monitor units. We conclude in this study that VMAT does not offer significant improvement of treatment for sino-nasal cancer over the existing IMRT techniques, but the findings may change with a larger sample of patients in this rare condition.
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Comparison of perioperative outcomes following open versus minimally invasive Ivor Lewis oesophagectomy at a single, high-volume centre.
Eur J Cardiothorac Surg
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With the increasing popularity of minimally invasive oesophageal resections, equivalence, if not superiority, to open techniques must be demonstrated. Here we compare our open and minimally invasive Ivor Lewis oesophagectomy (MIE) experience.
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JoVE Visualize is a tool created to match the last 5 years of PubMed publications to methods in JoVE's video library.

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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.