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Find video protocols related to scientific articles indexed in Pubmed.
Development of sol-gel icephobic coatings: effect of surface roughness and surface energy.
ACS Appl Mater Interfaces
PUBLISHED: 11-11-2014
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Sol-gel coatings with different roughness and surface energy were prepared on glass substrates. Methyl triethoxysilane (MTEOS), 3-Glycidyloxypropyl trimethoxysilane (GLYMO) and fluoroalkylsilane (FAS) were used to obtain a mechanically robust icephobic coating. Different amount of hydrophobic silica nano particles was added as fillers to introduce different roughness and surface energy to the coatings. The microstructure, roughness, and surface energy, together with elemental information and surface chemical state were investigated at room temperature. The contact angle and sliding angle were measured at different temperatures to correlate the wetting behavior at low temperature with the anti-icing performance. The ice adhesion shear strength was measured inside an ice chamber using a self-designed tester. The factors influencing the ice adhesion were discussed, and the optimum anti-icing performance found in the series of coatings. It was found that lower surface energy leads to lower ice adhesion regardless of the roughness, while the roughness plays a more complicated role. The wetting behavior of the droplet on surface changes as temperature decreases. The anti-icing performance is closely related to the anti-wetting property of the surfaces at sub-zero temperatures.
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Interlaboratory and between-specimen comparisons of diagnostic tests for leptospirosis in sheep and cattle.
J. Vet. Diagn. Invest.
PUBLISHED: 10-07-2014
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A study was performed to investigate interlaboratory test agreement between a research and a commercial veterinary diagnostic laboratory on blood and urine samples, and to investigate test agreement between blood, urine, and kidney samples (research laboratory) for leptospirosis diagnosis. Samples were sourced from 399 sheep and 146 beef cattle from a local abattoir. Interlaboratory agreement for real-time quantitative polymerase chain reaction (qPCR) results on urine samples was almost perfect (kappa = 0.90), despite the use of different amplification targets (DNA gyrase subunit B gene vs. 16s ribosomal RNA gene), chemistries (SYTO9 vs. TaqMan probe), and pre-PCR processing. Interlaboratory agreement for microscopic agglutination test (MAT) positivity was almost perfect (kappa = 0.93) for Leptospira borgpetersenii serovar Hardjo subtype Hardjobovis (Hardjobovis) but moderate (kappa = 0.53) for Leptospira interrogans serovar Pomona (Pomona). Among animals that had different titers recorded, higher Hardjobovis and lower Pomona titers were reported by the commercial laboratory than by the research laboratory (P < 0.005). These interlaboratory comparisons can assist researchers and diagnosticians in interpreting the sometimes discrepant test results. Within the research laboratory, the comparison of qPCR results on urine and kidney showed almost perfect agreement (kappa = 0.84), suggesting that the qPCR on these 2 specimens can be used interchangeably. The agreement between MAT positivity and urine and kidney qPCR results was fair (kappa = 0.32 and kappa = 0.33, respectively). However, the prevalence ratio of urine and kidney qPCR positivity in Hardjobovis-seropositive versus Hardjobovis-seronegative sheep indicated that Hardjobovis seropositivity found in sheep may be able to predict shedding or renal carriage.
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Bacteraemia incidence, causative organisms and resistance patterns, antibiotic strategies and outcomes in a single university hospital ICU: continuing improvement between 2000 and 2013.
J. Antimicrob. Chemother.
PUBLISHED: 09-03-2014
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The optimal duration of antibiotic treatment in patients with bloodstream infections remains contentious, with concerns regarding both undertreatment and the encouragement of antibiotic resistance. In our ICU we traditionally use short-course antibiotic monotherapy as the mainstay of treatment. We sought to document the impact of this strategy on pathogen type, resistance patterns and patient outcomes. A comparison was made against data collected during a similar exercise in 2000.
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Men who have sex with men in southern Vietnam report high levels of substance use and sexual risk behaviours but underutilise HIV testing services: a cross-sectional study.
Sex Transm Infect
PUBLISHED: 09-02-2014
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This study aims to investigate the levels and correlates of unprotected anal intercourse (UAI), drug and alcohol use, and HIV testing among Vietnamese men who have sex with men (MSM).
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Compromised motor control in children with DCD: A deficit in the internal model?-A systematic review.
Neurosci Biobehav Rev
PUBLISHED: 09-01-2014
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A viable hypothesis to explain the compromised motor ability of children with Developmental Coordination Disorder (DCD) suggests a fundamental deficit in their ability to utilize internal models for motor control. Dysfunction in this mode of control is thought to compromise their motor learning capabilities. The aim of this systematic review is to examine the available evidence for the internal modeling deficit (IMD) hypothesis. A systematic review using five databases identified 48 relevant articles. These studies were categorized according to the effector system involved in the evaluation of motor control and were evaluated for methodological quality. In most papers, DSM-IV-TR criteria for the classification of DCD were not completely fulfilled and possible attentional problems not accounted for. Results showed compromised control of overt and covert eye movements, dynamic postural control, manual control for tasks that vary in complexity, and for motor imagery of manual and whole-body postures. Importantly, this review shows support for general hypothesis that deficits of predictive control manifest in DCD across effector systems.
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RNA mango aptamer-fluorophore: a bright, high-affinity complex for RNA labeling and tracking.
ACS Chem. Biol.
PUBLISHED: 08-21-2014
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Because RNA lacks strong intrinsic fluorescence, it has proven challenging to track RNA molecules in real time. To address this problem and to allow the purification of fluorescently tagged RNA complexes, we have selected a high affinity RNA aptamer called RNA Mango. This aptamer binds a series of thiazole orange (fluorophore) derivatives with nanomolar affinity, while increasing fluorophore fluorescence by up to 1,100-fold. Visualization of RNA Mango by single-molecule fluorescence microscopy, together with injection and imaging of RNA Mango/fluorophore complex in C. elegans gonads demonstrates the potential for live-cell RNA imaging with this system. By inserting RNA Mango into a stem loop of the bacterial 6S RNA and biotinylating the fluorophore, we demonstrate that the aptamer can be used to simultaneously fluorescently label and purify biologically important RNAs. The high affinity and fluorescent properties of RNA Mango are therefore expected to simplify the study of RNA complexes.
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Baseline levels, and changes over time in body mass index and fasting insulin, and their relationship to change in metabolic trait clustering.
Metab Syndr Relat Disord
PUBLISHED: 07-09-2014
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Multiple abnormal metabolic traits are found together or "cluster" within individuals more often than is predicted by chance. The individual and combined role of adiposity and insulin resistance (IR) on metabolic trait clustering is uncertain. We tested the hypothesis that change in trait clustering is a function of both baseline level and change in these measures.
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Characterization of ice binding proteins from sea ice algae.
Methods Mol. Biol.
PUBLISHED: 05-24-2014
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Several polar microalgae are able to live and thrive in the extreme environment found within sea ice, where growing ice crystals may cause mechanical damage to the cells and reduce the organisms' living space. Among the strategies adopted by these organisms to cope with the harsh conditions in their environment, ice binding proteins (IBPs) seem to play a key role and possibly contribute to their success in sea ice. IBPs have the ability to control ice crystal growth. In nature they are widespread among sea ice microalgae, and their mechanism of function is of interest for manifold potential applications. Here we describe methods for a classical determination of the IBP activity (thermal hysteresis, recrystallization inhibition) and further methods for protein characterization (ice pitting assay, determination of the nucleating temperature).
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Nelson's syndrome: single centre experience using the linear accelerator (LINAC) for stereotactic radiosurgery and fractionated stereotactic radiotherapy.
J Clin Neurosci
PUBLISHED: 05-11-2014
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Nelson's syndrome is a unique clinical phenomenon of growth of a pituitary adenoma following bilateral adrenalectomies for the control of Cushing's disease. Primary management is surgical, with limited effective medical therapies available. We report our own institution's series of this pathology managed with radiation: prior to 1990, 12 patients were managed with conventional radiotherapy, and between 1990 and 2007, five patients underwent stereotactic radiosurgery (SRS) and two patients fractionated stereotactic radiotherapy (FSRT), both using the linear accelerator (LINAC). Tumour control was equivocal, with two of the five SRS patients having a reduction in tumour volume, one patient remaining unchanged, and two patients having an increase in volume. In the FSRT group, one patient had a decrease in tumour volume whilst the other had an increase in volume. Treatment related morbidity was low. Nelson's syndrome is a challenging clinical scenario, with a highly variable response to radiation in our series.
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Genomic catastrophes frequently arise in esophageal adenocarcinoma and drive tumorigenesis.
Nat Commun
PUBLISHED: 04-16-2014
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Oesophageal adenocarcinoma (EAC) incidence is rapidly increasing in Western countries. A better understanding of EAC underpins efforts to improve early detection and treatment outcomes. While large EAC exome sequencing efforts to date have found recurrent loss-of-function mutations, oncogenic driving events have been underrepresented. Here we use a combination of whole-genome sequencing (WGS) and single-nucleotide polymorphism-array profiling to show that genomic catastrophes are frequent in EAC, with almost a third (32%, n=40/123) undergoing chromothriptic events. WGS of 22 EAC cases show that catastrophes may lead to oncogene amplification through chromothripsis-derived double-minute chromosome formation (MYC and MDM2) or breakage-fusion-bridge (KRAS, MDM2 and RFC3). Telomere shortening is more prominent in EACs bearing localized complex rearrangements. Mutational signature analysis also confirms that extreme genomic instability in EAC can be driven by somatic BRCA2 mutations. These findings suggest that genomic catastrophes have a significant role in the malignant transformation of EAC.
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Standing the test of time: targeting thymidylate biosynthesis in cancer therapy.
Nat Rev Clin Oncol
PUBLISHED: 04-15-2014
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Over the past 60 years, chemotherapeutic agents that target thymidylate biosynthesis and the enzyme thymidylate synthase (TS) have remained among the most-successful drugs used in the treatment of cancer. Fluoropyrimidines, such as 5-fluorouracil and capecitabine, and antifolates, such as methotrexate and pemetrexed, induce a state of thymidylate deficiency and imbalances in the nucleotide pool that impair DNA replication and repair. TS-targeted agents are used to treat numerous solid and haematological malignancies, either alone or as foundational therapeutics in combination treatment regimens. We overview the pivotal discoveries that led to the rational development of thymidylate biosynthesis as a chemotherapeutic target, and highlight the crucial contribution of these advances to driving and accelerating drug development in the earliest era of cancer chemotherapy. The function of TS as well as the mechanisms and consequences of inhibition of this enzyme by structurally diverse classes of drugs with distinct mechanisms of action are also discussed. In addition, breakthroughs relating to TS-targeted therapies that transformed the clinical landscape in some of the most-difficult-to-treat cancers, such as pancreatic, colorectal and non-small-cell lung cancer, are highlighted. Finally, new therapeutic agents and novel mechanism-based strategies that promise to further exploit the vulnerabilities and target resistance mechanisms within the thymidylate biosynthesis pathway are reviewed.
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Molecular epidemiology of Mycobacterium avium subsp. paratuberculosis isolated from sheep, cattle and deer on New Zealand pastoral farms.
Prev. Vet. Med.
PUBLISHED: 04-09-2014
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The present study aimed to describe the molecular diversity of Mycobacterium avium subsp. paratuberculosis (MAP) isolates obtained from sheep, cattle (beef and dairy) and deer farms in New Zealand. A total of 206 independent MAP isolates (15 beef cattle, 89 dairy cattle, 35 deer, 67 sheep) were sourced from 172 species-mobs (15 beef cattle, 66 dairy cattle, 31 deer, 60 sheep). Seventeen subtypes were identified, using a combination of variable number of tandem repeats (VNTR) and short sequence repeat (SSR) methods. Rarefaction analysis, analysis of molecular variance (AMOVA), Fst pairwise comparisons and proportional similarity index (PSI) were used to describe subtype population richness, genetic structure and potential associations between livestock sectors and New Zealand two main islands (North and South). The rarefaction analysis suggests a significantly higher subtype richness in dairy cattle herds when compared to the other livestock sectors. AMOVA results indicate that the main source of subtype variation is attributable to the livestock sector from which samples were sourced suggesting that subtypes are generally sector-specific. The pairwise Fst results were similar, with low Fst values for island differences within a livestock sector when compared to between sector analyses, representing a low subtype differentiation between islands. However, for a given island, potential associations were seen between dominant subtypes and specific livestock sectors. Three subtypes accounted for 76% of the isolates. The most common of these was isolated from sheep and beef cattle in the North Island, the second most frequent subtype was mainly isolated from dairy cattle (either island), while the third most common subtype was associated with deer farmed in the South Island. The PSI analysis suggests similarities in subtypes sourced from sheep and beef cattle. This contrasted with the isolates sourced from other livestock sectors, which tended to present sector-specific subtypes. Sheep and beef cattle were mainly infected with MAP Type I, while dairy cattle and deer were almost exclusively infected with MAP Type II. However, when beef cattle and deer were both present at farm level, they harboured similar subtypes. This study indicates that cross-species transmission of MAP occurs on New Zealand farms although close contact between species appears to be required, as in the case of sheep and beef cattle which are commonly grazed together in New Zealand.
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Incident heart failure in relation to vascular disease: insights from the Health, Aging, and Body Composition Study.
Eur. J. Heart Fail.
PUBLISHED: 01-22-2014
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The contribution of heart failure (HF) unrelated to vascular disease to the overall HF burden in older adults is not well characterized. This was investigated in this study.
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Sero-prevalence and risk factors for leptospirosis in abattoir workers in New Zealand.
Int J Environ Res Public Health
PUBLISHED: 01-22-2014
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Leptospirosis is an important occupational disease in New Zealand. The objectives of this study were to determine risk factors for sero-prevalence of leptospiral antibodies in abattoir workers. Sera were collected from 567 abattoir workers and tested by microscopic agglutination for Leptospira interrogans sv. Pomona and Leptospira borgpetersenii sv. Hardjobovis. Association between prevalence and risk factors were determined by species specific multivariable analysis. Eleven percent of workers had antibodies against Hardjobovis or/and Pomona. Workers from the four sheep abattoirs had an average sero-prevalence of 10%-31%, from the two deer abattoirs 17%-19% and the two beef abattoirs 5%. The strongest risk factor for sero-positivity in sheep and deer abattoirs was work position. In sheep abattoirs, prevalence was highest at stunning and hide removal, followed by removal of the bladder and kidneys. Wearing personal protective equipment such as gloves and facemasks did not appear to protect against infection. Home slaughtering, farming or hunting were not significantly associated with sero-prevalence. There is substantial risk of exposure to leptospires in sheep and deer abattoirs in New Zealand and a persisting, but lower risk, in beef abattoirs. Interventions, such as animal vaccination, appear necessary to control leptospirosis as an occupational disease in New Zealand.
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Mild impairments of motor imagery skills in children with DCD.
Res Dev Disabil
PUBLISHED: 01-15-2014
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It has been hypothesized that the underlying mechanism of clumsy motor behaviour in children with Developmental Coordination Disorder (DCD) is caused by a deficit in the internal modelling for motor control. An internal modelling deficit can be shown on a behavioural level by a task that requires motor imagery. Motor imagery skills are suggested to be related to anticipatory action planning, but motor imagery and action planning have not been tested within the same child. In the present study, action planning and motor imagery skills were assessed in 82 children between 7 and 12 years of age. Twenty-one of these children met the criteria for DCD, which was assessed by the McCarron Assessment of Neuromuscular Development and 56 of these children were used in the control group. Motor imagery was tested by a mental rotation task of hands that were shown from a back and palm point of view. The results show that motor imagery is affected in children with DCD but only in conditions with complex task constraints (i.e., rotation of hand stimuli presented in palm view). These results provide partial support for the internal modelling deficit hypothesis. We were not able to elicit motor planning deficits in this group, however, and argue that more complex planning tasks may be needed to identify such deficits.
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Brain metastases associated with germ cell tumors may be treated with chemotherapy alone.
Cancer
PUBLISHED: 01-13-2014
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The management of brain metastases in patients with germ cell tumors remains controversial. The authors assessed the outcome in this patient group after the introduction of GAMEC chemotherapy (14-day cisplatin, high-dose methotrexate, etoposide, and actinomycin-D with filgrastim support) and cessation of the routine use of cranial irradiation.
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Executive systems constrain the flexibility of online control in children during goal-directed reaching.
Dev Neuropsychol
PUBLISHED: 01-11-2014
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We examined the influence of inhibitory load on online motor control in children. A sample of 129 school children was tested: younger, mid-age, and older children. Online control was assessed using a double-step perturbation paradigm across three trail types: non-jump, jump, and anti-jump. Results show that mid-aged children were able to implement online adjustments to jump trials as quickly as older children, but their performance on anti-jump trials regressed toward younger children. This suggests that rapid unfolding of executive systems during middle childhood may constrain the flexibility with which online control can be implemented, particularly when inhibitory demands are imposed.
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Comparative biology and expression of TENP, an egg protein related to the bacterial permeability-increasing family of proteins.
Gene
PUBLISHED: 01-10-2014
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The 'transiently expressed in neural precursors' (TENP) gene product is a member of the bacterial/permeability-increasing (BPI) family of antimicrobial proteins but was first identified as having a role in an early neurological event occurring in post-mitotic cells. However, recent characterisation of the egg white proteome has shown that TENP is an important egg component constituting ~0.1-0.5% of the total protein and suggesting it is expressed in the adult oviduct. In this study we confirmed quantitatively that the expression of TENP is largely confined to the tubular glands of the magnum of the oviduct, where egg white synthesis occurs, with around 10,000 times more expression than in the embryo where TENP was first identified. TENP expression is significantly increased with the administration of oestrogen or progesterone (P<0.001) and is reduced in regressed oviducts (P<0.001) demonstrating gonadal steroid control, typical of an oviduct and egg specific gene. A putative translational start site for TENP has been characterised and the evidence indicates that it is expressed as one predominant transcript. In comparison with the published sequence, insertion and deletion events have been identified causing a partial frame-shift that results in an altered amino acid sequence to that previously documented. TENP is conserved across divergent avian species being found in chicken, turkey, duck and zebra finch and its expression profile confirmed in both chicken and duck. Similarity searches have shown homology with the BPI-like family of innate immune genes, particularly with palate, lung and nasal epithelial clone (PLUNC) members of this family. We therefore believe that at least in adults the role of TENP is as a major component of egg, particularly the white and it is probable that it contributes to its antimicrobial function.
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A phase Ib study investigating the combination of everolimus and dovitinib in vascular endothelial growth factor refractory clear cell renal cancer.
Eur. J. Cancer
PUBLISHED: 01-03-2014
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Everolimus (mammalian target of rapmaycin (mTOR) inhibitor) and dovitinib (vascular endothelial growth factor (VEGF) and fibroblast growth factor 2 (FGF-2) inhibitor) demonstrate activity in metastatic clear cell renal cancer. The combination of these agents has a broad spectrum of relevant activity. The combination is explored in this phase Ib study.
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Large-scale solution synthesis of narrow graphene nanoribbons.
Nat Commun
PUBLISHED: 01-02-2014
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According to theoretical studies, narrow graphene nanoribbons with atomically precise armchair edges and widths of <2?nm have a bandgap comparable to that in silicon (1.1?eV), which makes them potentially promising for logic applications. Different top-down fabrication approaches typically yield ribbons with width >10?nm and have limited control over their edge structure. Here we demonstrate a novel bottom-up approach that yields gram quantities of high-aspect-ratio graphene nanoribbons, which are only ~1?nm wide and have atomically smooth armchair edges. These ribbons are shown to have a large electronic bandgap of ~1.3?eV, which is significantly higher than any value reported so far in experimental studies of graphene nanoribbons prepared by top-down approaches. These synthetic ribbons could have lengths of >100?nm and self-assemble in highly ordered few-micrometer-long 'nanobelts' that can be visualized by conventional microscopy techniques, and potentially used for the fabrication of electronic devices.
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A workflow to increase verification rate of chromosomal structural rearrangements using high-throughput next-generation sequencing.
BioTechniques
PUBLISHED: 01-01-2014
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Somatic rearrangements, which are commonly found in human cancer genomes, contribute to the progression and maintenance of cancers. Conventionally, the verification of somatic rearrangements comprises many manual steps and Sanger sequencing. This is labor intensive when verifying a large number of rearrangements in a large cohort. To increase the verification throughput, we devised a high-throughput workflow that utilizes benchtop next-generation sequencing and in-house bioinformatics tools to link the laboratory processes. In the proposed workflow, primers are automatically designed. PCR and an optional gel electrophoresis step to confirm the somatic nature of the rearrangements are performed. PCR products of somatic events are pooled for Ion Torrent PGM and/or Illumina MiSeq sequencing, the resulting sequence reads are assembled into consensus contigs by a consensus assembler, and an automated BLAT is used to resolve the breakpoints to base level. We compared sequences and breakpoints of verified somatic rearrangements between the conventional and high-throughput workflow. The results showed that next-generation sequencing methods are comparable to conventional Sanger sequencing. The identified breakpoints obtained from next-generation sequencing methods were highly accurate and reproducible. Furthermore, the proposed workflow allows hundreds of events to be processed in a shorter time frame compared with the conventional workflow.
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Trends in the breeding population of Adélie penguins in the Ross Sea, 1981-2012: a coincidence of climate and resource extraction effects.
PLoS ONE
PUBLISHED: 01-01-2014
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Measurements of the size of Adélie penguin (Pygoscelis adeliae) colonies of the southern Ross Sea are among the longest biologic time series in the Antarctic. We present an assessment of recent annual variation and trends in abundance and growth rates of these colonies, adding to the published record not updated for more than two decades. High angle oblique aerial photographic surveys of colonies were acquired and penguins counted for the breeding seasons 1981-2012. In the last four years the numbers of Adélie penguins in the Ross and Beaufort Island colonies (southern Ross Sea metapopulation) reached their highest levels since aerial counts began in 1981. Results indicated that 855,625 pairs of Adélie penguins established breeding territories in the western Ross Sea, with just over a quarter (28%) of those in the southern portion, constituting a semi-isolated metapopulation (three colonies on Ross Island, one on nearby Beaufort Island). The southern population had a negative per capita growth rate of -0.019 during 1981-2000, followed by a positive per capita growth rate of 0.067 for 2001-2012. Colony growth rates for this metapopulation showed striking synchrony through time, indicating that large-scale factors influenced their annual growth. In contrast to the increased colony sizes in the southern population, the patterns of change among colonies of the northern Ross Sea were difficult to characterize. Trends were similar to southern colonies until the mid-1990s, after which the signal was lost owing to significantly reduced frequency of surveys. Both climate factors and recovery of whale populations likely played roles in the trends among southern colonies until 2000, after which depletion of another trophic competitor, the Antarctic toothfish (Dissostichus mawsoni), may explain the sharp increasing trend evident since then.
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Antibiotic therapy for the treatment of methicillin-resistant Staphylococcus aureus (MRSA) in non surgical wounds.
Cochrane Database Syst Rev
PUBLISHED: 11-19-2013
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Non surgical wounds include chronic ulcers (pressure or decubitus ulcers, venous ulcers, diabetic ulcers, ischaemic ulcers), burns and traumatic wounds. The prevalence of methicillin-resistant Staphylococcus aureus (MRSA) colonisation (i.e. presence of MRSA in the absence of clinical features of infection such as redness or pus discharge) or infection in chronic ulcers varies between 7% and 30%. MRSA colonisation or infection of non surgical wounds can result in MRSA bacteraemia (infection of the blood) which is associated with a 30-day mortality of about 28% to 38% and a one-year mortality of about 55%. People with non surgical wounds colonised or infected with MRSA may be reservoirs of MRSA, so it is important to treat them, however, we do not know the optimal antibiotic regimen to use in these cases.
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Bayesian estimation of the sensitivity and specificity of individual fecal culture and Paralisa to detect Mycobacterium avium subspecies paratuberculosis infection in young farmed deer.
J. Vet. Diagn. Invest.
PUBLISHED: 10-08-2013
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A Bayesian latent class model was used to estimate the sensitivity and specificity of an immunoglobulin G1 serum enzyme-linked immunosorbent assay (Paralisa) and individual fecal culture to detect young deer infected with Mycobacterium avium subsp. paratuberculosis. Paired fecal and serum samples were collected, between July 2009 and April 2010, from 20 individual yearling (12-24-month-old) deer in each of 20 South Island and 18 North Island herds in New Zealand and subjected to culture and Paralisa, respectively. Two fecal samples and 16 serum samples from 356 North Island deer, and 55 fecal and 37 serum samples from 401 South Island deer, were positive. The estimate of individual fecal culture sensitivity was 77% (95% credible interval [CI] = 61-92%) with specificity of 99% (95% CI = 98-99.7%). The Paralisa sensitivity estimate was 19% (95% CI = 10-30%), with specificity of 94% (95% CI = 93-96%). All estimates were robust to variation of priors and assumptions tested in a sensitivity analysis. The data informs the use of the tests in determining infection status at the individual and herd level.
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Antibiotic therapy for the treatment of methicillin-resistant Staphylococcus aureus (MRSA) infections in surgical wounds.
Cochrane Database Syst Rev
PUBLISHED: 08-22-2013
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Methicillin-resistant Staphylococcus aureus (MRSA) infection after surgery is usually rare, but incidence can be up to 33% in certain types of surgery. Postoperative MRSA infection can occur as surgical site infections (SSI), chest infections, or bloodstream infections (bacteraemia). The incidence of MRSA SSIs varies from 1% to 33% depending upon the type of surgery performed and the carrier status of the individuals concerned. The optimal antibiotic regimen for the treatment of MRSA in surgical wounds is not known.
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Antibiotic prophylaxis for the prevention of methicillin-resistant Staphylococcus aureus (MRSA) related complications in surgical patients.
Cochrane Database Syst Rev
PUBLISHED: 08-21-2013
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Risk of methicillin-resistant Staphylococcus aureus (MRSA) infection after surgery is generally low, but affects up to 33% of patients after certain types of surgery. Postoperative MRSA infection can occur as surgical site infections (SSIs), chest infections, or bloodstream infections (bacteraemia). The incidence of MRSA SSIs varies from 1% to 33% depending upon the type of surgery performed and the carrier status of the individuals concerned. The optimal prophylactic antibiotic regimen for the prevention of MRSA after surgery is not known.
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Changes in lipoprotein particle number with ezetimibe/simvastatin coadministered with extended-release niacin in hyperlipidemic patients.
J Am Heart Assoc
PUBLISHED: 08-09-2013
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Combination therapy with ezetimibe/simvastatin (E/S) and extended-release niacin (N) has been reported to be safe and efficacious in concomitantly reducing low-density lipoprotein cholesterol and increasing high-density lipoprotein cholesterol in hyperlipidemic patients at high risk for atherosclerotic cardiovascular events. This analysis evaluated the effect of E/S coadministered with N on low-density lipoprotein particle number (LDL-P) and high-density lipoprotein particle number (HDL-P) as assessed by nuclear magnetic resonance (NMR) spectroscopy in patients with type IIa or IIb hyperlipidemia.
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Staphylococcus aureus bloodstream infection: A pooled analysis of five prospective, observational studies.
J. Infect.
PUBLISHED: 06-28-2013
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Staphylococcus aureus bacteraemia is a common, often fatal infection. Our aim was to describe how its clinical presentation varies between populations and to identify common determinants of outcome.
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An 18-month follow-up investigation of motor coordination and working memory in primary school children.
Hum Mov Sci
PUBLISHED: 06-21-2013
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The aim of the current study was to examine the relationship between motor coordination and visual working memory in children aged 5-11years. Participants were 18 children with movement difficulty and 41 control children, assessed at baseline and following an 18-month time period. The McCarron Assessment of Neuromuscular Development provided a measure of motor skills and the CogState One-Back task was used to assess visual working memory. Multi-level mixed effects linear regressions were used to assess the relationship between fine motor skills, gross motor skills, and visual working memory. The results revealed that for children with movement difficulty, better fine motor skills at baseline significantly predicted greater One-Back accuracy and greater (i.e., faster) speed at 18-month follow-up. Conversely, fine motor skills at baseline did not predict One-Back accuracy and speed for control children. However, for both groups, greater One-Back accuracy at baseline predicted better fine and gross motor skills at follow-up. These findings have important implications for the assessment and treatment of children referred for motor difficulties and/or working memory difficulties.
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Managing and preventing outbreaks of Gram-negative infections in UK neonatal units.
Arch. Dis. Child. Fetal Neonatal Ed.
PUBLISHED: 06-21-2013
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De novo guidance on the management of Gram-negative bacteria outbreaks in UK neonatal units was developed in 2012 by a Department of Health, England Antimicrobial Resistance and Healthcare Associated Infection working group. The recommendations included activation of an organisational response and establishing a control team when an outbreak is suspected; screening for the specific organism only during an outbreak; undertaking multidisciplinary reviews of cleaning routines, hand hygiene and Gram-negative bacteria transmission risks; considering deep-cleaning; cohorting colonised and infected babies preferably but not necessarily in isolation cubicles; and considering reducing beds or closing a unit to new admissions as a way of improving spacing and staff:patient ratios until the outbreak is under control. The group advised establishing mechanisms to communicate effectively across the network; informing parents of the outbreak as early as possible, and providing prewritten infection outbreak information sheets. For prevention of outbreaks, the group advised meeting national staffing and cot-spacing requirements; following a Water Action Plan; using infection reduction care bundles and benchmarking; and introducing breast milk early and limiting antibiotic use.
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Highly selective gas sensor arrays based on thermally reduced graphene oxide.
Nanoscale
PUBLISHED: 05-11-2013
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The electrical properties of reduced graphene oxide (rGO) have been previously shown to be very sensitive to surface adsorbates, thus making rGO a very promising platform for highly sensitive gas sensors. However, poor selectivity of rGO-based gas sensors remains a major problem for their practical use. In this paper, we address the selectivity problem by employing an array of rGO-based integrated sensors instead of focusing on the performance of a single sensing element. Each rGO-based device in such an array has a unique sensor response due to the irregular structure of rGO films at different levels of organization, ranging from nanoscale to macroscale. The resulting rGO-based gas sensing system could reliably recognize analytes of nearly the same chemical nature. In our experiments rGO-based sensor arrays demonstrated a high selectivity that was sufficient to discriminate between different alcohols, such as methanol, ethanol and isopropanol, at a 100% success rate. We also discuss a possible sensing mechanism that provides the basis for analyte differentiation.
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Hybrid technique for posterior lumbar interbody fusion: a combination of open decompression and percutaneous pedicle screw fixation.
Orthop Surg
PUBLISHED: 05-10-2013
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The authors describe a hybrid technique that involves a combination of open decompression and posterior lumbar interbody fusion (PLIF) and percutaneously inserted pedicle screws. This technique allows performance of PLIF and decompression via a midline incision and approach without compromising operative time and visualization. Furthermore, compared to standard open decompression, this approach reduces post-operative wound pain because the small midline incision significantly reduces muscle trauma by obviating the need to dissect the paraspinal muscles off the facet joint complex and by avoiding posterolateral fusion, thus requiring limited lateral muscle dissection off the transverse processes. A series of patients with Grade I-II spondylolisthesis at L4-5 and moderate-severe canal/foraminal stenosis underwent midline PLIF at L4-5, with closure of the midline incision. Percutaneous pedicle screws were inserted, thereby minimizing local muscle trauma, reduction of the spondylolisthesis being performed by using a pedicle screw construct. Rods were inserted percutaneously to link the L4 and L5 pedicle screws. Image intensification was used to confirmed satisfactory screw placement and reduction of spondylolisthesis. The results of a prospective study comparing a standard open decompression and fusion technique for spondylolisthesis versus the minimally invasive hybrid technique are discussed. The minimally invasive technique resulted in shorter hospital stay, earlier mobilization and reduced postoperative narcotic usage. The long-term clinical outcomes were equivalent in the two groups.
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The type, level, and distribution of microorganisms within the ward environment: a zonal analysis of an intensive care unit and a gastrointestinal surgical ward.
Infect Control Hosp Epidemiol
PUBLISHED: 04-11-2013
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OBJECTIVE.?To investigate the distribution of hospital pathogens within general and critical care ward environments and to determine the most significant bacterial reservoirs within each ward type. DESIGN.?Prospective 4-month microbiological survey. SETTING.?The intensive care unit (ICU) and gastrointestinal (GI) surgical ward of a London teaching hospital. PATIENTS.?Sampling was conducted in and around the bed space of 166 different patients (99 in the ICU and 67 in the GI ward). METHODS.?Conventional agar contact methodology was used to sample 123 predetermined sites twice a week for 17 weeks. Sixty-one surfaces were located within the ICU, and 62 were located within the GI ward. Each surface was located within a theoretical zone of increasing distance from the patient. Aerobic colony counts were determined, and confirmatory testing was conducted on all presumptive pathogens. RESULTS.?Regardless of ward type, surfaces located closest to the patient, specifically those associated with the bed (side rails, bed control, and call button), were the most heavily contaminated. Elsewhere, the type of surfaces contaminated differed with ward type. In the ICU, bacteria were most likely to be on surfaces that were regularly touched by healthcare workers (e.g., telephones and computer keyboards). In the GI ward, where the patients were mobile, the highest numbers of bacteria (including potential nosocomial pathogens) were on surfaces that were mainly touched by patients, particularly their toilet and shower facilities. CONCLUSIONS.?In terms of cleaning, a hospital should not be considered a single entity. Different ward types should be treated as separate environments, and cleaning protocols should be adjusted accordingly.
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Noise, variability, and motor performance in developmental coordination disorder.
Dev Med Child Neurol
PUBLISHED: 04-04-2013
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Variability and noise are a natural part of the neuromuscular system, and can occur at multiple levels. However, excessive neural noise in the motor system makes the problem of control much harder. Disruption of basic sensory inputs will exacerbate the problem, impacting ones sense of position in space (or body schema) and the ability of the motor system to predict its own dynamics. So-called predictive control is fundamental to movement efficiency and accuracy, but has been shown to be poorly developed in children with motor problems like developmental coordination disorder. These children manifest a core deficit in predictive control, which is expressed by high levels of variability across tasks, and at the level of movement kinematics, for example patterns of inter-limb coordination. As such, they rely heavily on feedback mechanisms to exert control, the outcome being slower and more laboured movements, and reduced responsiveness to changes in the environment. We discuss these issues of high variability and noise in developmental coordination disorder in relation to motor prediction, and with an eye to remediation. Issues of task scheduling and use of augmented feedback are important considerations for therapists when treating these children.
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Ochronotic osteoarthropathy in a mouse model of alkaptonuria, and its inhibition by nitisinone.
Ann. Rheum. Dis.
PUBLISHED: 03-19-2013
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Alkaptonuria (AKU) is a rare metabolic disease caused by deficiency of homogentisate 1,2 dioxygenase, an enzyme involved in tyrosine catabolism, resulting in increased circulating homogentisic acid (HGA). Over time HGA is progressively deposited as a polymer (termed ochronotic pigment) in collagenous tissues, especially the cartilages of weight bearing joints, leading to severe joint disease.
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Orexin in the chicken hypothalamus: immunocytochemical localisation and comparison of mRNA concentrations during the day and night, and after chronic food restriction.
Brain Res.
PUBLISHED: 03-17-2013
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In mammals Orexin-A and -B are neuropeptides involved in the hypothalamic regulation of diverse physiological functions including food intake and the sleep-wake cycle. This generalisation was investigated in meat-(broiler) and layer-type juvenile domestic chickens by immunocytochemical localisation of orexin A/B in the hypothalamus, and by measurements of hypothalamic hypocretin mRNA which encodes for orexin A/B after chronic food restriction, and during the sleep-wake cycle. Orexin immunoreactive fibres were observed throughout the hypothalamus with cell bodies in and around the paraventricular nucleus. No differences were observed in the pattern of immunoreactivity using anti- human orexin-A, or -B antisera. The amount of hypothalamic hypocretin mRNA in food -restricted broilers was higher than in broilers fed ad libitum, but the same as in layer- type hens fed ad libitum. Hypothalamic hypocretin mRNA was increased (P<0.01) in 12-week-old broilers fed 25% of their ad libitum intake between 6-12 weeks of age. No difference in hypothalamic hypocretin mRNA was seen in 12-week-old layer- type hens when they were awake (1-2h after lights on) or sleeping (1-2h after lights off). It is concluded that in the chicken, we could not find evidence that hypothalamic orexin plays a role in the sleep-wake cycle and it may be involved in aspects of energy balance.
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Effect of ABT-335 (fenofibric acid) on meal-induced oxidative stress in patients with metabolic syndrome.
Atherosclerosis
PUBLISHED: 03-11-2013
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Examine the effect of ABT-335 (fenofibric acid) on postprandial lipemia and susceptibility of plasma lipoproteins to Cu(++)-mediated oxidation in patients with metabolic syndrome.
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Decreased expression of the satiety signal receptor CCKAR is responsible for increased growth and body weight during the domestication of chickens.
Am. J. Physiol. Endocrinol. Metab.
PUBLISHED: 02-26-2013
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Animal domestication has resulted in changes in growth and size. It has been suggested that this may have involved selection for differences in appetite. Divergent growth between chickens selected for egg laying or meat production is one such example. The neurons expressing AGRP and POMC in the basal hypothalamus are important components of appetite regulation, as are the satiety feedback pathways that carry information from the intestine, including CCK and its receptor CCKAR (CCK1 receptor). Using 16 generations of a cross between a fast and a relatively slow growing strain of chicken has identified a region on chromosome 4 downstream of the CCKAR gene, which is responsible for up to a 19% difference in body weight at 12 wk of age. Animals possessing the high-growth haplotype at the locus have lower expression of mRNA and immunoreactive CCKAR in the brain, intestine, and exocrine organs, which is correlated with increased levels of orexigenic AGRP in the hypothalamus. Animals with the high-growth haplotype are resistant to the anorectic effect of exogenously administered CCK, suggesting that their satiety set point has been altered. Comparison with traditional breeds shows that the high-growth haplotype has been present in the founders of modern meat-type strains and may have been selected early in domestication. This is the first dissection of the physiological consequences of a genetic locus for a quantitative trait that alters appetite and gives us an insight into the domestication of animals. This will allow elucidation of how differences in appetite occur in birds and also mammals.
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The development of rapid online control in children aged 6-12years: Reaching performance.
Hum Mov Sci
PUBLISHED: 02-20-2013
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Rapid online control during reaching has an important bearing on movement accuracy and flexibility. It is surprising then that few studies have investigated the development of rapid online control in children. In this study, we were particularly interested in age-related changes in the nature of motor control in response to visual perturbation. We compared the performance of younger (6-7years of age), mid-aged (8-9), and older (10-12) children, as well as healthy young adults using a double-step reaching task. Participants were required to make target-directed reaching movements in near space, while also responding to visual perturbations that occurred at movement onset for a small percentage of trials. Results showed that both the older and mid-aged children corrected their reaching in response to the unexpected shifts in target location significantly faster than younger children, manifest by reduced time to correction. In turn, the responses of adults were faster than older children in terms of movement time and on kinematic measures such as time to correction and time to peak velocity. These results indicate that the capacity to utilize forward estimates of limb position in the service of online control of early perturbations to ballistic (or rapid) reaching develops in a non-linear fashion, progressing rapidly between early and middle childhood, showing a degree of stability over mid and later childhood, but then evidence for continued refinement between childhood and young adulthood. The pattern of change after childhood and into early adolescence requires further investigation, particularly during the rapid phase of physical growth that accompanies puberty.
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Impaired online control in children with developmental coordination disorder reflects developmental immaturity.
Dev Neuropsychol
PUBLISHED: 02-16-2013
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The present study aimed to clarify whether a reduced ability to correct movements in-flight observed in children with developmental coordination disorder (DCD) reflects a developmental immaturity or deviance from the typical trajectory. Eighteen children with DCD (8-12 years), 18 age-matched controls, and 12 younger controls (5-7 years) completed a double-step reaching task. Compared to older controls, children with DCD and younger controls showed similarly prolonged reaching when the target unexpectedly shifted at movement onset and were equally slow to correct their reaching trajectory. These results suggest that impaired online control in DCD reflects developmental immaturity, possibly implicating the parietal-cerebellar cortices.
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Clinical components and associated behavioural aspects of a complex healthcare intervention: Multi-methods study of selective decontamination of the digestive tract in critical care.
Aust Crit Care
PUBLISHED: 01-14-2013
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This study sought to identify and describe the clinical and behavioural components (e.g. the what, how, when, where and by whom) of selective decontamination of the digestive tract (SDD) as routinely implemented in the care of critically ill patients.
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Sustained inhibition of deacetylases is required for the antitumor activity of the histone deactylase inhibitors panobinostat and vorinostat in models of colorectal cancer.
Invest New Drugs
PUBLISHED: 01-09-2013
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Despite compelling preclinical data in colorectal cancer (CRC), the efficacy of HDACIs has been disappointing in the clinic. The goal of this study was to evaluate the effectiveness of vorinostat and panobinostat in a dose- and exposure-dependent manner in order to better understand the dynamics of drug action and antitumor efficacy. In a standard 72 h drug exposure MTS assay, notable concentration-dependent antiproliferative effects were observed in the IC50 range of 1.2-2.8 ?mol/L for vorinostat and 5.1-17.5 nmol/L for panobinostat. However, shorter clinically relevant exposures of 3 or 6 h failed to elicit any significant growth inhibition and in most cases a >24 h exposure to vorinostat or panobinostat was required to induce a sigmoidal dose-response. Similar results were observed in colony formation assays where ? 24 h of exposure was required to effectively reduce colony formation. Induction of acetyl-H3, acetyl-H4 and p21 by vorinostat were transient and rapidly reversed within 12 h of drug removal. In contrast, panobinostat-induced acetyl-H3, acetyl-H4, and p21 persisted for 48 h after an initial 3 h exposure. Treatment of HCT116 xenografts with panobinostat induced significant increases in acetyl-H3 and downregulation of thymidylate synthase after treatment. Although HDACIs exert both potent growth inhibition and cytotoxic effects when CRC cells were exposed to drug for ? 24 h, these cells demonstrate an inherent ability to survive HDACI concentrations and exposure times that exceed those clinically achievable. Continued efforts to develop novel HDACIs with improved pharmacokinetics/phamacodynamics, enhanced intratumoral delivery and class/isoform-specificity are needed to improve the therapeutic potential of HDACIs and HDACI-based combination regimens in solid tumors.
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Somatic point mutation calling in low cellularity tumors.
PLoS ONE
PUBLISHED: 01-01-2013
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Somatic mutation calling from next-generation sequencing data remains a challenge due to the difficulties of distinguishing true somatic events from artifacts arising from PCR, sequencing errors or mis-mapping. Tumor cellularity or purity, sub-clonality and copy number changes also confound the identification of true somatic events against a background of germline variants. We have developed a heuristic strategy and software (http://www.qcmg.org/bioinformatics/qsnp/) for somatic mutation calling in samples with low tumor content and we show the superior sensitivity and precision of our approach using a previously sequenced cell line, a series of tumor/normal admixtures, and 3,253 putative somatic SNVs verified on an orthogonal platform.
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Inhibition of dUTPase induces synthetic lethality with thymidylate synthase-targeted therapies in non-small cell lung cancer.
Mol. Cancer Ther.
PUBLISHED: 12-15-2011
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Chemotherapies that target thymidylate synthase (TS) continue to see considerable clinical expansion in non-small cell lung cancer (NSCLC). One drawback to TS-targeted therapies is drug resistance and subsequent treatment failure. Novel therapeutic and biomarker-driven strategies are urgently needed. The enzyme deoxyuridine triphosphate nucleotidohydrolase (dUTPase) is reported to protect tumor cells from aberrant misincorporation of uracil during TS inhibition. The goal of this study was to investigate the expression and significance of dUTPase in mediating response to TS-targeted agents in NSCLC. The expression of dUTPase in NSCLC cell lines and clinical specimens was measured by quantitative real-time reverse transcriptase PCR and immunohistochemistry. Using a validated RNA interference approach, dUTPase was effectively silenced in a panel of NSCLC cell lines and response to the fluoropyrimidine fluorodeoxyuridine (FUdR) and the antifolate pemetrexed was analyzed using growth inhibition and clonogenic assays. Apoptosis was analyzed by flow cytometry. Significant variation in the quantity and cellular expression of dUTPase was observed, including clear evidence of overexpression in NSCLC cell line models and tumor specimens at the mRNA and protein level. RNA interference-mediated silencing of dUTPase significantly sensitized NSCLC cells to growth inhibition induced by FUdR and pemetrexed. This sensitization was accompanied by a significant expansion of intracellular dUTP pools and significant decreases in NSCLC cell viability evaluated by clonogenicity and apoptotic analyses. Together, these results strongly suggest that uracil misincorporation is a potent determinant of cytotoxicity to TS inhibition in NSCLC and that inhibition of dUTPase is a mechanism-based therapeutic approach to significantly enhance the efficacy of TS-targeted chemotherapeutic agents.
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One-pot near-ambient temperature syntheses of aryl(difluoroenol) derivatives from trifluoroethanol.
Org. Biomol. Chem.
PUBLISHED: 11-07-2011
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Difluoroalkenylzinc reagents prepared from 1-(2-methoxy-ethoxymethoxy)-2,2,2-trifluoroethane and 1-(N,N-diethylcarbamoyloxy)-2,2,2-trifluoroethane at ice bath temperatures underwent Negishi coupling with a range of aryl halides in a convenient one pot procedure. While significant differences between the enol acetal and carbamate reagents were revealed, the Negishi protocol compared very favourably with alternative coupling procedures in terms of overall yields from trifluoroethanol.
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Use of virtual reality in rehabilitation of movement in children with hemiplegia--a multiple case study evaluation.
Disabil Rehabil
PUBLISHED: 10-06-2011
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To evaluate the feasibility and therapeutic effect of engaging children of differing neuromotor and cognitive ability in a virtual reality (VR) tabletop workspace designed to improve upper-limb function.
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Ethnic differences in cardiovascular risks and mortality in atherothrombotic disease: insights from the Reduction of Atherothrombosis for Continued Health (REACH) registry.
Mayo Clin. Proc.
PUBLISHED: 10-04-2011
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To determine whether ethnic-specific differences in the prevalence of cardiovascular risk factors and outcomes exist worldwide among individuals with stable arterial disease.
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Common cancer stem cell gene variants predict colon cancer recurrence.
Clin. Cancer Res.
PUBLISHED: 09-14-2011
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Recent evidence suggests that cancer stem cells (CSC) are responsible for key elements of colon cancer progression and recurrence. Germline variants in CSC genes may result in altered gene function and/or activity, thereby causing interindividual differences in a patients tumor recurrence capacity and chemoresistance. We investigated germline polymorphisms in a comprehensive panel of CSC genes to predict time to tumor recurrence (TTR) in patients with stage III and high-risk stage II colon cancer.
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Antimicrobial sutures and prevention of surgical site infection: assessment of the safety of the antiseptic triclosan.
Int Wound J
PUBLISHED: 08-19-2011
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This article is based on a second Hygienist Panel meeting held in London on 16-17 June 2010. The Panel discussed the current use of antimicrobials and care bundles in the prevention of surgical site infection; the need to comply with good antibiotic stewardship, to reduce the risk of antibiotic-resistant and emergent organisms; and the need to revisit the use of antiseptics. The discussion was driven by concerns of the use of triclosan, which had been raised by a publication from the Scientific Committee on Consumer Products of the Directorate General for Health and Consumers, European Commission. Uncertainties that excessive use of triclosan for preservation and in cosmetics could select naturally resistant environmental organisms or induce reduced triclosan-susceptibility or antibiotic resistance were considered. It was concluded that the uses of triclosan with demonstrable health benefits, as in some medical applications (such as antimicrobial sutures), need to be distinguished from those where there is no proven benefit, such as its use in certain consumer products. The addition of triclosan to a product must be substantiated in any claim of preventive or therapeutic health benefit. Triclosan is the most widely studied biocide and this same level of information should be available for other topically used antimicrobials, which are widely used in surgical practice and chronic wound care.
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Association of adiponectin with left ventricular mass in blacks: the Jackson Heart Study.
Circ Heart Fail
PUBLISHED: 08-12-2011
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Blacks have a higher prevalence of left ventricular hypertrophy than whites. Several population-based studies have reported an inverse association between adiponectin and left ventricular mass (LVM); however, the relationship between adiponectin levels and LVM has yet to be defined in blacks. The Jackson Heart Study cohort provides an opportunity to test the hypothesis that the inverse association between adiponectin and LVM may be modified by risk factors common among blacks.
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Pharmacogenetic angiogenesis profiling for first-line Bevacizumab plus oxaliplatin-based chemotherapy in patients with metastatic colorectal cancer.
Clin. Cancer Res.
PUBLISHED: 07-26-2011
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There is substantial germline genetic variability within angiogenesis pathway genes, thereby causing interindividual differences in angiogenic capacity and resistance to antiangiogenesis therapy. We investigated germline polymorphisms in genes involved in VEGF-dependent and -independent angiogenesis pathways to predict clinical outcome and tumor response in metastatic colorectal cancer (mCRC) patients treated with bevacizumab and oxaliplatin-based chemotherapy.
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Sequential FDG-PET/CT as a biomarker of response to Sunitinib in metastatic clear cell renal cancer.
Clin. Cancer Res.
PUBLISHED: 07-08-2011
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To test the hypothesis that sequential (18)F-fluorodeoxyglucose-positron emission tomography/computed tomography (FDG-PET/CT) is a correlative marker in metastatic clear cell renal cancer (mRCC), patients were treated with sunitinib. Three sequential scans were conducted to determine whether the timing of the investigation was relevant.
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Development of a high pressure automated lag time apparatus for experimental studies and statistical analyses of nucleation and growth of gas hydrates.
Rev Sci Instrum
PUBLISHED: 07-05-2011
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Nucleation in a supercooled or a supersaturated medium is a stochastic event, and hence statistical analyses are required for the understanding and prediction of such events. The development of reliable statistical methods for quantifying nucleation probability is highly desirable for applications where control of nucleation is required. The nucleation of gas hydrates in supercooled conditions is one such application. We describe the design and development of a high pressure automated lag time apparatus (HP-ALTA) for the statistical study of gas hydrate nucleation and growth at elevated gas pressures. The apparatus allows a small volume (?150 ?l) of water to be cooled at a controlled rate in a pressurized gas atmosphere, and the temperature of gas hydrate nucleation, T(f), to be detected. The instrument then raises the sample temperature under controlled conditions to facilitate dissociation of the gas hydrate before repeating the cooling-nucleation cycle again. This process of forming and dissociating gas hydrates can be automatically repeated for a statistically significant (>100) number of nucleation events. The HP-ALTA can be operated in two modes, one for the detection of hydrate in the bulk of the sample, under a stirring action, and the other for the detection of the formation of hydrate films across the water-gas interface of a quiescent sample. The technique can be applied to the study of several parameters, such as gas pressure, cooling rate and gas composition, on the gas hydrate nucleation probability distribution for supercooled water samples.
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Preoperative gabapentin for acute post-thoracotomy analgesia: a randomized, double-blinded, active placebo-controlled study.
Pain Pract
PUBLISHED: 06-16-2011
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The role of preoperative gabapentin in postoperative pain management is not clear, particularly in patients receiving regional blockade. Patients undergoing thoracotomy benefit from epidural analgesia but still may experience significant postoperative pain. We examined the effect of preoperative gabapentin in thoracotomy patients.
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Evaluation of a SYTO9 real-time polymerase chain reaction assay to detect and identify pathogenic Leptospira species in kidney tissue and urine of New Zealand farmed deer.
J. Vet. Diagn. Invest.
PUBLISHED: 06-07-2011
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A SYTO9 real-time polymerase chain reaction assay for detection of pathogenic Leptospira spp. based on amplification of DNA gyrase subunit B (gyrB) gene has been optimized and evaluated for sensitivity and specificity on kidney and urine samples of New Zealand farmed deer. The detection limit was 10(3) cells/ml (2-10 copies/reaction). Comparison of the assay on deer kidneys (n = 268) with culture as the gold standard revealed a sensitivity and specificity of 85% and 99.2%, respectively. For deer urine (n = 113), the assay was compared with known inoculated samples and revealed a sensitivity and specificity of 96.7% and 100%, respectively. The assay was applied for quantifying pathogenic leptospires shed naturally in deer urine and revealed a detectable concentration of 3.7 × 10(3) to 1.7 × 10(6) cells/ml. To assess the assays capability for identifying pathogenic Leptospira spp., 14 field isolates of L. borgpetersenii serovar Hardjo-bovis and L. interrogans serovar Pomona were amplified for polymerase chain reaction (PCR) product, purified, and sequenced. When compared with the National Center for Biotechnology Information database, sequence data matched with L. borgpetersenii serovar Hardjo-bovis in 13 samples and L. interrogans serovar Pomona in 1 sample, which was consistent with the microscopic agglutination test (MAT). Sequence analysis of purified PCR product amplified directly from kidney and urine samples also yielded serovar-comparable MAT results. Results suggest that the assay is rapid, sensitive, and specific for detection of pathogenic leptospires in deer clinical samples. The developed assay can also be used for estimating the concentration of leptospires and identifying Leptospira spp. in combination with DNA sequencing.
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Sensitivity and test-retest reliability of the international shopping list test in assessing verbal learning and memory in mild Alzheimers disease.
Arch Clin Neuropsychol
PUBLISHED: 05-25-2011
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The International Shopping List Test (ISLT) was developed specifically to assess verbal list learning and memory in people from different language and cultural backgrounds. In this paper, we describe three studies that examined the sensitivity and reliability of the ISLT in assessing verbal list learning and memory impairment in English-speaking people with mild Alzheimers disease (AD) and evaluated whether measures of retention-weighted recall (RWR) provided greater sensitivity and/or reliability relative to conventional list learning performance measures (e.g., free recall). In Study 1, we compared ISLT performance between patients with AD and matched controls and found that AD patients showed a large magnitude impairment on all ISLT performance measures (Cohens d values >2). The RWR measure was more sensitive to detecting AD-related impairment than the free recall measure for Trial 1, although the most sensitive measures of the ISLT were free recall from Trial 3 and delayed recall. In Study 2, we compared RWR and free recall measures between 10- and 12-word versions of the ISLT, but found no difference between performance measures for the different list lengths. In Study 3, we evaluated test-retest reliabilities of the different outcome measures derived from the ISLT and found that measures of free recall had higher reliabilities than the RWR measures. Taken together, results of these studies suggest that measures of total free recall during learning trials and delayed recall from the 12-word version of the ISLT provide the greatest sensitivity to detecting verbal list learning and memory impairment in AD and that this task shows good test-retest reliability.
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Genome sequence of an Australian kangaroo, Macropus eugenii, provides insight into the evolution of mammalian reproduction and development.
Marilyn B Renfree, Anthony T Papenfuss, Janine E Deakin, James Lindsay, Thomas Heider, Katherine Belov, Willem Rens, Paul D Waters, Elizabeth A Pharo, Geoff Shaw, Emily S W Wong, Christophe M Lefèvre, Kevin R Nicholas, Yoko Kuroki, Matthew J Wakefield, Kyall R Zenger, Chenwei Wang, Malcolm Ferguson-Smith, Frank W Nicholas, Danielle Hickford, Hongshi Yu, Kirsty R Short, Hannah V Siddle, Stephen R Frankenberg, Keng Yih Chew, Brandon R Menzies, Jessica M Stringer, Shunsuke Suzuki, Timothy A Hore, Margaret L Delbridge, Hardip R Patel, Amir Mohammadi, Nanette Y Schneider, Yanqiu Hu, William O'Hara, Shafagh Al Nadaf, Chen Wu, Zhi-Ping Feng, Benjamin G Cocks, Jianghui Wang, Paul Flicek, Stephen M J Searle, Susan Fairley, Kathryn Beal, Javier Herrero, Dawn M Carone, Yutaka Suzuki, Sumio Sugano, Atsushi Toyoda, Yoshiyuki Sakaki, Shinji Kondo, Yuichiro Nishida, Shoji Tatsumoto, Ion Mandiou, Arthur Hsu, Kaighin A McColl, Benjamin Lansdell, George Weinstock, Elizabeth Kuczek, Annette McGrath, Peter Wilson, Artem Men, Mehlika Hazar-Rethinam, Allison Hall, John Davis, David Wood, Sarah Williams, Yogi Sundaravadanam, Donna M Muzny, Shalini N Jhangiani, Lora R Lewis, Margaret B Morgan, Geoffrey O Okwuonu, San Juana Ruiz, Jireh Santibanez, Lynne Nazareth, Andrew Cree, Gerald Fowler, Christie L Kovar, Huyen H Dinh, Vandita Joshi, Chyn Jing, Fremiet Lara, Rebecca Thornton, Lei Chen, Jixin Deng, Yue Liu, Joshua Y Shen, Xing-Zhi Song, Janette Edson, Carmen Troon, Daniel Thomas, Amber Stephens, Lankesha Yapa, Tanya Levchenko, Richard A Gibbs, Desmond W Cooper, Terence P Speed, Asao Fujiyama, Jennifer A M Graves, Rachel J O'Neill, Andrew J Pask, Susan M Forrest, Kim C Worley.
Genome Biol.
PUBLISHED: 05-23-2011
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We present the genome sequence of the tammar wallaby, Macropus eugenii, which is a member of the kangaroo family and the first representative of the iconic hopping mammals that symbolize Australia to be sequenced. The tammar has many unusual biological characteristics, including the longest period of embryonic diapause of any mammal, extremely synchronized seasonal breeding and prolonged and sophisticated lactation within a well-defined pouch. Like other marsupials, it gives birth to highly altricial young, and has a small number of very large chromosomes, making it a valuable model for genomics, reproduction and development.
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Post hoc subgroup analysis of the HEART2D trial demonstrates lower cardiovascular risk in older patients targeting postprandial versus fasting/premeal glycemia.
Diabetes Care
PUBLISHED: 05-18-2011
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To identify the Hyperglycemia and Its Effect After Acute Myocardial Infarction on Cardiovascular Outcomes in Patients With Type 2 Diabetes Mellitus (HEART2D) trial subgroups with treatment difference.
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A novel fluorescence-based assay for the rapid detection and quantification of cellular deoxyribonucleoside triphosphates.
Nucleic Acids Res.
PUBLISHED: 05-16-2011
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Current methods for measuring deoxyribonucleoside triphosphates (dNTPs) employ reagent and labor-intensive assays utilizing radioisotopes in DNA polymerase-based assays and/or chromatography-based approaches. We have developed a rapid and sensitive 96-well fluorescence-based assay to quantify cellular dNTPs utilizing a standard real-time PCR thermocycler. This assay relies on the principle that incorporation of a limiting dNTP is required for primer-extension and Taq polymerase-mediated 5-3 exonuclease hydrolysis of a dual-quenched fluorophore-labeled probe resulting in fluorescence. The concentration of limiting dNTP is directly proportional to the fluorescence generated. The assay demonstrated excellent linearity (R(2)?>?0.99) and can be modified to detect between ?0.5 and 100?pmol of dNTP. The limits of detection (LOD) and quantification (LOQ) for all dNTPs were defined as <0.77 and <1.3?pmol, respectively. The intra-assay and inter-assay variation coefficients were determined to be <4.6% and <10%, respectively with an accuracy of 100?±?15% for all dNTPs. The assay quantified intracellular dNTPs with similar results obtained from a validated LC-MS/MS approach and successfully measured quantitative differences in dNTP pools in human cancer cells treated with inhibitors of thymidylate metabolism. This assay has important application in research that investigates the influence of pathological conditions or pharmacological agents on dNTP biosynthesis and regulation.
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Outcomes in unresectable and locally advanced resected cholangiocarcinoma.
Expert Rev Anticancer Ther
PUBLISHED: 05-11-2011
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Patients with cholangiocarcinomas often present with unresectable disease, which is associated with a poor clinical outcome and survival. A number of palliative options are available to patients; the evaluated article presented experience from a single institution of treating cholangiocarcinoma, either unresectable or locally advanced, with conformal radiotherapy and concurrent chemotherapy. Patients who had received biliary radiation for cholangiocarcinoma were identified from the hospital database, and information on the patients sourced from notes and reports. In total, 20 patients with a diagnosis of biliary tract cancer were included and received radical conformal radiotherapy with concurrent cisplatin/5-fluorouracil and sequential gemcitabine. The median overall survival was 20.4 months and the relapse-free survival was 9.6 months. Treatment failure within the radiotherapy field was recorded in 45% of patients; adverse events were minimal. This study adds to the retrospective data available regarding the management of patients with biliary tract carcinomas, and we have found in our own cohort of 45 patients that gemcitabine/platinum was a more effective combination than monotherapy.
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Calbindin 2 (CALB2) regulates 5-fluorouracil sensitivity in colorectal cancer by modulating the intrinsic apoptotic pathway.
PLoS ONE
PUBLISHED: 04-28-2011
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The role of the calcium binding protein, Calbindin 2 (CALB2), in regulating the response of colorectal cancer (CRC) cells to 5-Fluorouracil (5-FU) was investigated. Real-time RT-PCR and Western blot analysis revealed that CALB2 mRNA and protein expression were down-regulated in p53 wild-type and p53 null isogenic HCT116 CRC cell lines following 48 h and 72 h 5-FU treatment. Moreover, 5-FU-induced apoptosis was significantly reduced in HCT116 and LS174T CRC cell lines in which CALB2 expression had been silenced. Further investigation revealed that CALB2 translocated to the mitochondria following 5-FU treatment and that 5-FU-induced loss of mitochondrial membrane potential (??(m)) was abrogated in CALB2-silenced cells. Furthermore, CALB2 silencing decreased 5-FU-induced cytochrome c and smac release from the mitochondria and also decreased 5-FU-induced activation of caspases 9 and 3/7. Of note, co-silencing of XIAP overcame 5-FU resistance in CALB2-silenced cells. Collectively, these results suggest that following 5-FU treatment in CRC cell lines, CALB2 is involved in apoptosis induction through the intrinsic mitochondrial pathway. This indicates that CALB2 may be an important mediator of 5-FU-induced cell death. Moreover, down-regulation of CALB2 in response to 5-FU may represent an intrinsic mechanism of resistance to this anti-cancer drug.
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A phase II study of mitomycin, fluorouracil, folinic acid, and irinotecan (MFI) for the treatment of transitional cell carcinoma of the bladder.
Urol. Oncol.
PUBLISHED: 04-10-2011
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Cisplatin-based chemotherapy is standard care for metastatic transitional cell carcinoma (TCC) of the urinary tract. However it is not appropriate for all patients, particularly those with poor renal function. There is no clear consensus on the optimal regimen for these individuals or for those after cisplatin failure. Here we present data using mitomycin, 5-fluorouracil, and irinotecan (MFI) in these patients.
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Gender-specific genomic profiling in metastatic colorectal cancer patients treated with 5-fluorouracil and oxaliplatin.
Pharmacogenomics
PUBLISHED: 04-05-2011
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Survival and response rates in metastatic colorectal cancer remain poor, despite advances in drug development. There is increasing evidence to suggest that gender-specific differences may contribute to poor clinical outcome. We tested the hypothesis that genomic profiling of metastatic colorectal cancer is dependent on gender.
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The dual EGFR/HER2 inhibitor lapatinib synergistically enhances the antitumor activity of the histone deacetylase inhibitor panobinostat in colorectal cancer models.
Cancer Res.
PUBLISHED: 04-04-2011
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As key molecules that drive progression and chemoresistance in gastrointestinal cancers, epidermal growth factor receptor (EGFR) and HER2 have become efficacious drug targets in this setting. Lapatinib is an EGFR/HER2 kinase inhibitor suppressing signaling through the RAS/RAF/MEK (MAP/ERK kinase)/MAPK (mitogen-activated protein kinase) and PI3K (phosphoinositide 3-kinase)/AKT pathways. Histone deacetylase inhibitors (HDACi) are a novel class of agents that induce cell cycle arrest and apoptosis following the acetylation of histone and nonhistone proteins modulating gene expression and disrupting HSP90 function inducing the degradation of EGFR-pathway client proteins. This study sought to evaluate the therapeutic potential of combining lapatinib with the HDACi panobinostat in colorectal cancer (CRC) cell lines with varying EGFR/HER2 expression and KRAS/BRAF/PIK3CA mutations. Lapatinib and panobinostat exerted concentration-dependent antiproliferative effects in vitro (panobinostat range 7.2-30 nmol/L; lapatinib range 7.6-25.8 ?mol/L). Combined lapatinib and panobinostat treatment interacted synergistically to inhibit the proliferation and colony formation in all CRC cell lines tested. Combination treatment resulted in rapid induction of apoptosis that coincided with increased DNA double-strand breaks, caspase-8 activation, and PARP cleavage. This was paralleled by decreased signaling through both the PI3K and MAPK pathways and increased downregulation of transcriptional targets including NF-?B1, IRAK1, and CCND1. Panobinostat treatment induced downregulation of EGFR, HER2, and HER3 mRNA and protein through transcriptional and posttranslational mechanisms. In the LoVo KRAS mutant CRC xenograft model, the combination showed greater antitumor activity than either agent alone, with no apparent increase in toxicity. Our results offer preclinical rationale warranting further clinical investigation combining HDACi with EGFR and HER2-targeted therapies for CRC treatment.
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Social complexity and nesting habits are factors in the evolution of antimicrobial defences in wasps.
PLoS ONE
PUBLISHED: 04-03-2011
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Microbial diseases are important selective agents in social insects and one major defense mechanism is the secretion of cuticular antimicrobial compounds. We hypothesized that given differences in group size, social complexity, and nest type the secretions of these antimicrobials will be under different selective pressures. To test this we extracted secretions from nine wasp species of varying social complexity and nesting habits and assayed their antimicrobial compounds against cultures of Staphylococcus aureus. These data were then combined with phylogenetic data to provide an evolutionary context. Social species showed significantly higher (18x) antimicrobial activity than solitary species and species with paper nests showed significantly higher (11x) antimicrobial activity than those which excavated burrows. Mud-nest species showed no antimicrobial activity. Solitary, burrow-provisioning wasps diverged at more basal nodes of the phylogenetic trees, while social wasps diverged from the most recent nodes. These data suggest that antimicrobial defences may have evolved in response to ground-dwelling pathogens but the most important variable leading to increased antimicrobial strength was increase in group size and social complexity.
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Epidemiology, antibiotic resistance trends and the cost of enteric fever in East London, 2005-2010.
Travel Med Infect Dis
PUBLISHED: 03-14-2011
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Enteric fever seen in the UK has usually been acquired abroad. The cost to the NHS of treating enteric fever cases is not known. Data on the epidemiology of enteric fever, inpatient treatment costs and the public health management is needed to make decisions regarding the cost benefit considerations of introducing targeted prevention strategies.
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Clinical management of Staphylococcus aureus bacteraemia.
Lancet Infect Dis
PUBLISHED: 03-05-2011
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Staphylococcus aureus bacteraemia is one of the most common serious bacterial infections worldwide. In the UK alone, around 12,500 cases each year are reported, with an associated mortality of about 30%, yet the evidence guiding optimum management is poor. To date, fewer than 1500 patients with S aureus bacteraemia have been recruited to 16 controlled trials of antimicrobial therapy. Consequently, clinical practice is driven by the results of observational studies and anecdote. Here, we propose and review ten unanswered clinical questions commonly posed by those managing S aureus bacteraemia. Our findings define the major areas of uncertainty in the management of S aureus bacteraemia and highlight just two key principles. First, all infective foci must be identified and removed as soon as possible. Second, long-term antimicrobial therapy is required for those with persistent bacteraemia or a deep, irremovable focus. Beyond this, the best drugs, dose, mode of delivery, and duration of therapy are uncertain, a situation compounded by emerging S aureus strains that are resistant to old and new antibiotics. We discuss the consequences on clinical practice, and how these findings define the agenda for future clinical research.
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A distinct DNA methylation profile associated with microsatellite and chromosomal stable sporadic colorectal cancers.
Int. J. Cancer
PUBLISHED: 03-03-2011
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Aberrant DNA methylation, microsatellite instability (MSI) and chromosomal instability (CIN) are well-characterised molecular features of sporadic colorectal cancers (CRCs). In addition to CpG island methylator phenotype (CIMP) associated with MSI, an intermediate methylation subgroup is also a feature of non-MSI cancers. A large proportion of CRCs have no evidence of either MSI or CIN, here called Microsatellite and Chromosomal Stable (MACS), and require their methylation profile to be established. The clinical and molecular features of 170 sporadic CRC patients were investigated and stratified into MSI, CIN and MACS groups. MACS were most often found in the left colon and had a significantly lower BRAF mutation frequency (p < 0.001) compared with MSI. MACS had better survival [hazard ratio (HR) = 0.244, p = 0.017] compared with CIN, but were similar to MSI. The methylation status of 1,505 CpG loci from cancer-related genes was analysed in a subset of CRCs (n = 44 normal-tumour pairs) and compared with CIN, MSI and MACS status. Using two-way hierarchical clustering, three subgroups were identified, which associated with CIN, MSI and MACS status. Using significance analysis of microarray, 16 CpG loci demonstrating methylation changes associated with MACS were identified. A combination of six loci identified MACS with 81% sensitivity and 93% specificity. This result now requires independent validation. Hypomethylation of a CpG locus within the sonic hedgehog (SHH) promoter correlated with increased gene expression and was associated significantly with MACS cancers. In conclusion, we propose that MACS have distinct clinicopathological features and can be distinguished from other CRCs by a specific set of methylation loci.
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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.

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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.