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Find video protocols related to scientific articles indexed in Pubmed.
Conformal organohalide perovskites enable lasing on spherical resonators.
ACS Nano
PUBLISHED: 10-17-2014
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Conformal integration of semiconductor gain media is broadly important in on-chip optical communication technology. Here we deploy atomic layer deposition to create conformally deposited organohalide perovskites-an attractive semiconducting gain medium-with the goal of achieving coherent light emission on spherical optical cavities. We demonstrate the high quality of perovskite gain media fabricated with this method, achieving optical gain in the nanosecond pulse regime with a threshold for amplified spontaneous emission of 65 ± 8 ?J cm(-2). Through variable stripe length measurements, we report a net modal gain of 125 ± 22 cm(-1) and a gain bandwidth of 50 ± 14 meV. Leveraging the high quality of the gain medium, we conformally coat silica microspheres with perovskite to form whispering gallery mode optical cavities and achieve lasing.
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Common risky behaviours checklist: a tool to assist nurse supervisors to assess unsafe practice.
J Nurs Manag
PUBLISHED: 10-04-2014
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To describe the development of the Common Risky Behaviour Checklist, a tool to aid nurse supervisors in determining when a nurse may be questionably fit to perform, particularly in cases of substance abuse.
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Elagolix, an oral GnRH antagonist, versus subcutaneous depot medroxyprogesterone acetate for the treatment of endometriosis: effects on bone mineral density.
Reprod Sci
PUBLISHED: 09-23-2014
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This randomized double-blind study, with 24-week treatment and 24-week posttreatment periods, evaluated the effects of elagolix (150 mg every day, 75 mg twice a day) versus subcutaneous depot medroxyprogesterone acetate (DMPA-SC) on bone mineral density (BMD), in women with endometriosis-associated pain (n = 252). All treatments induced minimal mean changes from baseline in BMD at week 24 (elagolix 150 mg: -0.11%/-0.47%, elagolix 75 mg: -1.29%/-1.2%, and DMPA-SC: 0.99%/-1.29% in the spine and total hip, respectively), with similar or less changes at week 48 (posttreatment). Elagolix was associated with improvements in endometriosis-associated pain, assessed with composite pelvic signs and symptoms score (CPSSS) and visual analogue scale, including statistical noninferiority to DMPA-SC in dysmenorrhea and nonmenstrual pelvic pain components of the CPSSS. The most common adverse events (AEs) in elagolix groups were headache, nausea, and nasopharyngitis, whereas the most common AEs in the DMPA-SC group were headache, nausea, upper respiratory tract infection, and mood swings. This study showed that similar to DMPA-SC, elagolix treatment had minimal impact on BMD over a 24-week period and demonstrated similar efficacy on endometriosis-associated pain.
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A Phase III, Multicenter, Randomized, Double-blind, Placebo-controlled, Parallel-group Study of 2 Dosing Regimens of Fostamatinib in Patients with Rheumatoid Arthritis with an Inadequate Response to a Tumor Necrosis Factor-? Antagonist.
J. Rheumatol.
PUBLISHED: 09-15-2014
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Our 24-week study (NCT01197755; OSKIRA-3) compared the efficacy and safety of fostamatinib versus placebo in patients taking background methotrexate treatment with active rheumatoid arthritis (RA) and an inadequate response to a single tumor necrosis factor-? antagonist.
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Perovskite Thin Films via Atomic Layer Deposition.
Adv. Mater. Weinheim
PUBLISHED: 08-28-2014
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A new method to deposit perovskite thin films which benefit from the thickness control and conformality of atomic layer deposition (ALD) is detailed. A seed layer of ALD PbS is place-exchanged with PbI2 and subsequently CH3 NH3 PbI3 perovskite. These films show promising optical properties, with gain coefficients of 3200 ± 830 cm(-1) .
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Phase II study of accelerated hypofractionated three-dimensional conformal radiotherapy for stage T1-3 N0 M0 non-small cell lung cancer: NCIC CTG BR.25.
J. Natl. Cancer Inst.
PUBLISHED: 08-01-2014
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A multi-institutional phase II trial was performed to assess a hypofractionated accelerated radiotherapy regimen for early stage non-small cell lung cancer (NSCLC) in an era when stereotactic body radiotherapy was not widely available.
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The role of advocacy in the national strategy for maternal death review in Nigeria.
Int J Gynaecol Obstet
PUBLISHED: 06-21-2014
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Strategic advocacy has played a substantial role in the development and implementation of maternal death review (MDR) in Nigeria. Stakeholders that include the Society of Gynaecology and Obstetrics of Nigeria have partnered with the Federal Ministry of Health to ensure a robust arrangement that will guarantee the success of MDR in this country. Consequently, it is envisaged that the program will both contribute to a sustainable reduction in the maternal mortality ratio and promote improvements in maternal health care. The Nigerian experience indicates that the influence of stakeholders, such as professional organizations, is essential to drive the development of MDR programs through provision of advocacy and technical support. The current convergence of factors-including global support, political will, technical innovations, and increased financial resources-provides an ideal opportunity to make MDR a reality for all countries.
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The relationship between rash, tumour KRAS mutation status and clinical and quality of life outcomes in patients with advanced colorectal cancer treated with cetuximab in the NCIC CTG/AGITG CO.17.
Acta Oncol
PUBLISHED: 02-05-2014
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The NCIC CTG/AGITG CO.17 trial demonstrated that cetuximab monotherapy improved overall and progression-free survival (OS and PFS) in patients previously treated for advanced colorectal cancer. A strong relationship was observed between benefit from cetuximab and development of rash. In this analysis, the association of rash and benefit from cetuximab is explored and presented by KRAS mutation status.
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Segmentation of epidermal tissue with histopathological damage in images of haematoxylin and eosin stained human skin.
BMC Med Imaging
PUBLISHED: 02-03-2014
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Digital image analysis has the potential to address issues surrounding traditional histological techniques including a lack of objectivity and high variability, through the application of quantitative analysis. A key initial step in image analysis is the identification of regions of interest. A widely applied methodology is that of segmentation. This paper proposes the application of image analysis techniques to segment skin tissue with varying degrees of histopathological damage. The segmentation of human tissue is challenging as a consequence of the complexity of the tissue structures and inconsistencies in tissue preparation, hence there is a need for a new robust method with the capability to handle the additional challenges materialising from histopathological damage.
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Systematic analysis of the factors that adversely affect the rate of cell accumulation in mouse embryos during their culture in vitro.
Reprod. Biol. Endocrinol.
PUBLISHED: 01-23-2014
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Retarded embryo growth is a pervasive effect of culture in vitro.
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The exit of mouse embryonic fibroblasts from the cell-cycle changes the nature of solvent exposure of the 5'-methylcytosine epitope within chromatin.
PLoS ONE
PUBLISHED: 01-01-2014
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The methylation of CpG dinucleotides is a pervasive epigenetic signature with critical roles governing genomic stability and lineage-specific patterns of gene expression. Reprogramming the patterns of CpG methylation accompanies key developmental transitions and the onset of some pathologies, such as cancer. In this study we show that levels of immuno-detectable 5meC decreased as mouse embryonic fibroblasts withdraw from the cell-cycle (became mitotically quiescent), but increased as they aged in culture. Two pools of 5meC epitope were found to exist, one solvent exposed after acid-induced denaturation of chromatin and another that required the additional step of tryptic digestion for detection. Proliferative cells displayed a relatively greater accumulation of detectable 5meC within the trypsin-sensitive pool than did quiescent cells. A substantial proportion of the 5meC was associated with a large number of heterochromatic foci scattered throughout nuclei, yet much of this was masked in a trypsin-sensitive manner, particularly in young proliferative cells. This study showed that the growth status of cells changed the level of solvent exposure of 5meC in fibroblasts and the long-accepted conventional methods of immunolocalization underestimate the level of 5meC in cells. This resulted in an artefactual assessment of the levels and patterns of nuclear localization of the antigen. The use of an additional tryptic digestion step improved antigen retrieval and revealed a more dynamic response of 5meC levels and distribution patterns to changes in the cell's growth state. This discovery will provide a basis for investigating the role of changes in chromatin structure that underlie this dynamism.
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RHPS4 G-quadruplex ligand induces anti-proliferative effects in brain tumor cells.
PLoS ONE
PUBLISHED: 01-01-2014
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Telomeric 3' overhangs can fold into a four-stranded DNA structure termed G-quadruplex (G4), a formation which inhibits telomerase. As telomerase activation is crucial for telomere maintenance in most cancer cells, several classes of G4 ligands have been designed to directly disrupt telomeric structure.
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The Oxford Renal (OxRen) cross-sectional study of chronic kidney disease in the UK.
BMJ Open
PUBLISHED: 12-19-2013
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Chronic kidney disease (CKD) diagnosed with objective measures of kidney damage and function has been recognised as a major public health burden. Independent of age, sex, ethnicity and comorbidity, strong associations exist between cardiovascular disease, mortality, morbidity and CKD, defined by reduced glomerular filtration rate and increased urinary albumin excretion. Detection of CKD within the population is therefore a priority for health systems.
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Comparison of the antibacterial activity of essential oils and extracts of medicinal and culinary herbs to investigate potential new treatments for irritable bowel syndrome.
BMC Complement Altern Med
PUBLISHED: 11-21-2013
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Irritable bowel syndrome (IBS) is a common functional gastrointestinal disorder, which may result from alteration of the gastrointestinal microbiota following gastrointestinal infection, or with intestinal dysbiosis or small intestinal bacterial overgrowth. This may be treated with antibiotics, but there is concern that widespread antibiotic use might lead to antibiotic resistance. Some herbal medicines have been shown to be beneficial, but their mechanism(s) of action remain incompletely understood. To try to understand whether antibacterial properties might be involved in the efficacy of these herbal medicines, and to investigate potential new treatments for IBS, we have conducted a preliminary study in vitro to compare the antibacterial activity of the essential oils of culinary and medicinal herbs against the bacterium, Esherichia coli.
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Paf receptor expression in the marsupial embryo and endometrium during embryonic diapause.
Reproduction
PUBLISHED: 10-15-2013
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The control of reactivation from embryonic diapause in the tammar wallaby (Macropus eugenii) involves sequential activation of the corpus luteum, secretion of progesterone that stimulates endometrial secretion and subsequent changes in the uterine environment that activate the embryo. However, the precise signals between the endometrium and the blastocyst are currently unknown. In eutherians, both the phospholipid Paf and its receptor, platelet-activating factor receptor (PTAFR), are present in the embryo and the endometrium. In the tammar, endometrial Paf release in vitro increases around the time of the early progesterone pulse that occurs around the time of reactivation, but whether Paf can reactivate the blastocyst is unknown. We cloned and characterised the expression of PTAFR in the tammar embryo and endometrium at entry into embryonic diapause, during its maintenance and after reactivation. Tammar PTAFR sequence and protein were highly conserved with mammalian orthologues. In the endometrium, PTAFR was expressed at a constant level in the glandular epithelium across all stages and in the luminal epithelium during both diapause and reactivation. Thus, the presence of the receptor appears not to be a limiting factor for Paf actions in the endometrium. However, the low levels of PTAFR in the embryo during diapause, together with its up-regulation and subsequent internalisation at reactivation, supports earlier results suggesting that endometrial Paf could be involved in reactivation of the tammar blastocyst from embryonic diapause.
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Post-mortem CT findings in a case of necrotizing cellulitis of the floor of the mouth (Ludwig angina).
Forensic Sci Med Pathol
PUBLISHED: 09-25-2013
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Ludwig angina is a rare but potentially lethal infection of the submandibular space that can cause significant upper airway obstruction. We report a case of undiagnosed Ludwig angina that progressed rapidly to death. Ludwig angina was suspected after post-mortem computed tomography (PMCT) found swollen mylohyoid muscle with stranding in subcutaneous fat, thickening of deep fascia, and local lymphadenopathy. Subsequently, an autopsy revealed woody induration of the submental region and liquefactive necrosis of the mylohyoid muscle, confirming the diagnosis. It is likely that the dental abscess identified on PMCT was the source of infection. Multiple invasive medical procedures were performed on the subject by the ambulance crew prior to his death. PMCT assisted further in determining procedural success.
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Observational study of ezetimibe discontinuation in primary care practices in the UK.
Curr Med Res Opin
PUBLISHED: 09-23-2013
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Abstract Objective: We investigated the circumstances of ezetimibe discontinuation as its prescribing had been discouraged in some publications. Research design and methods: Adults on stable lipid-modifying therapy (LMT) including ezetimibe, who then had >8 weeks cessation in their prescribed ezetimibe regimen (2010-2011) were identified from THIN UK primary care database. Lipid values and parallel changes to other LMT were described overall and in a sub-group with a history of diabetes, cardiovascular disease or familial hypercholesterolaemia (high-risk group). Results: Ezetimibe therapy stopped in 7087 patients after a mean of 38 months; 67.0% were in the high-risk group. No lipid readings were recorded for 16.1% of patients in the year before and 26.2% in the year after ezetimibe stopped; 11.0% and 12.4% in the high-risk group respectively. In the prior year, 60.2% patients with any lipid reading had a total cholesterol (T-cholesterol) <5?mmol/l and 59.2% had a T-cholesterol <5?mmol/l and LDL-cholesterol <3?mmol/l. In the high-risk group, 66.8% had a T-cholesterol <5?mmol/l, 38.9% had either a T-cholesterol <4 or a LDL-cholesterol <2?mmol/l and 29.4% had reached both targets. In both populations, 42% patients had 6 months follow-up after ezetimibe stopped with no change to other LMT. An LMT change within 8 weeks (19%) was usually a new statin while 27% overall had a further ezetimibe prescription after 8-26 weeks. Limitations: Only absolute lipid values were included, as percentage change from baseline level may not be reliable. The study included a larger proportion of patients in Scotland relative to the UK population. Conclusions: Prescribed ezetimibe often stopped without either a recent lipid value or attainment of optimal, or sometimes minimum, lipid targets. Patients did not always receive parallel intensification of other LMT or a further ezetimibe prescription within 6 months.
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Gefitinib versus placebo in completely resected non-small-cell lung cancer: results of the NCIC CTG BR19 study.
J. Clin. Oncol.
PUBLISHED: 08-26-2013
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Survival of patients with completely resected non-small-cell lung cancer (NSCLC) is unsatisfactory, and in 2002, the benefit of adjuvant chemotherapy was not established. This phase III study assessed the impact of postoperative adjuvant gefitinib on overall survival (OS).
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Nebulization of corticosteroids to asthmatic children: Large variation in dose inhaled.
Respirology
PUBLISHED: 08-20-2013
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Despite problems associated with assessing the clinical effect and side effects of nebulized corticosteroids, little is known of the amount of drug that is inhaled by children with asthma or how this is affected by different drug formulations. The aim of this study was to test the hypothesis that children with asthma inhale the same proportion of the prescribed dose of nebulized fluticasone, beclomethasone dipropionate (BDP) and flunisolide.
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Elagolix Treatment for Endometriosis-Associated Pain: Results from a Phase 2, Randomized, Double-Blind, Placebo-Controlled Study.
Reprod Sci
PUBLISHED: 07-24-2013
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This Phase 2 study evaluated the safety and efficacy of elagolix for treating endometriosis-associated pain. A total of 155 women with laparoscopically confirmed endometriosis were randomized to placebo, elagolix 150 mg, or elagolix 250 mg once daily for 12 weeks. Placebo patients were rerandomized to elagolix and elagolix patients continued their dosing assignment for 12 additional weeks; the primary efficacy measure was changed from baseline in the monthly mean numerical rating scale for pain at week 12. Monthly mean (standard error of the mean) reductions were greater with elagolix versus placebo (-1.19 ± 0.18, -1.25 ± 0.18, and -0.88 ± 0.18 for elagolix 150 mg, 250 mg, and placebo, respectively); differences were not statistically significant. Monthly mean dysmenorrhea and nonmenstrual pelvic pain scores were reduced with elagolix, with significant differences for dysmenorrhea at weeks 8 and 12 versus placebo (P < .05). Minimal bone mineral density changes were observed with elagolix treatment. In women with endometriosis-associated pain, elagolix demonstrated an acceptable efficacy and safety profile in this Phase 2 study.
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Non-invasive visualisation and volume estimation of maggot masses using computed tomography scanning.
Int. J. Legal Med.
PUBLISHED: 06-15-2013
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There is limited understanding of the actual temperatures that maggots experience during growth. The impact of maggot mass heating on their growth rates cannot be properly factored into maggot growth rate models, thus limiting the accuracy of forensic entomology estimates. One of the major factors contributing to mass heating is the mass size; however, measuring mass volume is problematic as masses quickly become disturbed when probing them to measure their depth and width. Furthermore, many masses are deep within the body cavity and are inaccessible. This study examined the development of a non-invasive means for measuring mass volume using computed tomography(CT) scanning. It was found that CT can be used to visualise and measure the volume of maggot masses, and a series of rules for doing so were established. The level of agreement between mass measurements made by four ‘judges’ using CT volumetric analysis tools produced excellent reliability (ICC > 0.95). This high level of reliability was maintained when applied to masses of different sizes in experimental cups of meat and natural masses of mixed species on human bodies. Entomological features of mortuary CT scans are now routinely reported in forensic entomology casework in Victoria, Australia, as a result of our work.
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Phase III randomized, placebo-controlled study of cetuximab plus brivanib alaninate versus cetuximab plus placebo in patients with metastatic, chemotherapy-refractory, wild-type K-RAS colorectal carcinoma: the NCIC Clinical Trials Group and AGITG CO.20 Tr
J. Clin. Oncol.
PUBLISHED: 05-20-2013
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The antiepidermal growth factor receptor monoclonal antibody cetuximab has improved survival in patients with metastatic, chemotherapy-refractory, wild-type K-RAS colorectal cancer. The addition of brivanib, a tyrosine kinase inhibitor targeting vascular endothelial growth factor receptor and fibroblast growth factor receptor, to cetuximab has shown encouraging early clinical activity.
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The use of computed tomography in determining developmental changes, anomalies, and trauma of the thyroid cartilage.
Forensic Sci Med Pathol
PUBLISHED: 05-04-2013
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Recognition of injury to the hyoid bone and thyroid and cricoid cartilages is intrinsic to post-mortem examination. Due to its increasing brittleness with age the thyroid cartilage is particularly susceptible to injury following neck trauma, although there is inconsistency in the patterns of injury reported. In this study computed tomography scans of the head and neck of 431 deceased persons (235 males and 196 females) between the ages of 1 day and 100 years (mean age 35.93 ± 24.15), and including 25 victims of hangings, were examined to reveal the pattern of age-related change and the types of injury that occurred. Thyroid cartilage anomalies likely to cause confusion and be misinterpreted as trauma-related are documented. Angulation of the thyroid cartilage horns was found to change with age, and it is suggested this may be a significant factor in traumatic neck injury. Unlike in previous reports, the average age of hanging victims with fractures to the thyroid cartilage was 34 years. The base of the superior horn was the most common fracture site and in 50 % of hanging cases was associated with a ligature positioned on the thyrohyoid membrane or thyroid lamina. Although an age-related relationship exists it was not possible to establish narrow age-prediction ranges from calcification of the thyroid cartilage.
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Findings of routine apical margin biopsy during robot-assisted radical prostatectomy.
J Laparoendosc Adv Surg Tech A
PUBLISHED: 04-27-2013
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Intraoperative biopsy of the apical margin during radical prostatectomy has been recommended as a way to reduce the positive margin rate at this location. However, the enhanced visibility of the apex during robot-assisted radical prostatectomy (RARP) may obviate this need, allowing for the preservation of maximal urethral length. We assessed pathologic findings of routine apical margin biopsy intraoperative frozen section (IFS) during RARP.
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Folded-light-path colloidal quantum dot solar cells.
Sci Rep
PUBLISHED: 03-28-2013
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Colloidal quantum dot photovoltaics combine low-cost solution processing with quantum size-effect tuning to match absorption to the solar spectrum. Rapid advances have led to certified solar power conversion efficiencies of over 7%. Nevertheless, these devices remain held back by a compromise in the choice of quantum dot film thickness, balancing on the one hand the need to maximize photon absorption, mandating a thicker film, and, on the other, the need for efficient carrier extraction, a consideration that limits film thickness. Here we report an architecture that breaks this compromise by folding the path of light propagating in the colloidal quantum dot solid. Using this method, we achieve a substantial increase in short-circuit current, ultimately leading to improved power conversion efficiency.
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Ciliary dyskinesia is an early feature of respiratory syncytial virus infection.
Eur. Respir. J.
PUBLISHED: 03-21-2013
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Respiratory syncytial virus (RSV) is a major cause of respiratory disease. There are conflicting accounts of the response of human epithelial cells to RSV and a lack of data on its effect on ciliary function. Our aim was to study the early stages of RSV infection of primary human basal and ciliated cultures.Using high speed video microscopy, we found that ciliary beat frequency was unaffected by RSV infection over 72 hours, however, ciliary dyskinesia significantly (P<0.05) increased within 24 hours of infection. Transmission electron microscopy revealed that ultrastructural abnormalities were confined to ciliated cells, including increased cilia loss and mitochondrial damage. Confocal immunofluorescence microscopy showed RSV antigen gradually spread from the cell surface to the ciliary tip of infected cells over three days. Interestingly, ciliated cultures secreted fewer viruses than basal (progenitor) cell cultures and produced a chemokine response focused on recruitment of neutrophils.This study highlights differences in infection models and underscores the need to further to explore the role of ciliated cells in the establishment of RSV infection. Increased ciliary dyskinesia combined with ciliary loss and epithelial damage is likely to result in reduced mucociliary clearance early in the infective process.
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The effect of ethanol and acetaldehyde on brain ependymal and respiratory ciliary beat frequency.
Cilia
PUBLISHED: 03-01-2013
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Ethanol has been shown to stimulate the beat frequency of respiratory cilia at concentrations encountered during social drinking, while one of its metabolites, acetaldehyde, has been shown to cause a marked decrease in ciliary beat frequency. The aim of this study was to determine whether short-term exposure to ethanol stimulated ependymal cilia and whether exposure to acetaldehyde had a toxic effect on ependymal and respiratory cilia.
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Evidence HDAC9 genetic variant associated with ischemic stroke increases risk via promoting carotid atherosclerosis.
Stroke
PUBLISHED: 02-28-2013
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A novel association between a single nucleotide polymorphism on chromosome 7p21.1 and large-vessel ischemic stroke was recently identified. The most likely underlying gene is histone deacetylase 9 (HDAC9). The mechanism by which HDAC9 increases stroke risk is not clear; both vascular and neuronal mechanisms have been proposed.
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Detailed analysis of patients with metastasis to the prostatic anterior fat pad lymph nodes: a multi-institutional study.
J. Urol.
PUBLISHED: 02-15-2013
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Lymph nodes in the prostatic anterior fat pad rarely harbor metastatic disease. Therefore, the characteristics of patients with prostatic anterior fat pad lymph node metastasis are not well described in the literature. We identified the perioperative characteristics and assessed the clinical outcomes of patients with prostatic anterior fat pad lymph node metastasis.
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5-Methylcytosine and 5-hydroxymethylcytosine each provide epigenetic information to the mouse zygote.
PLoS ONE
PUBLISHED: 01-01-2013
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Covalent modification of cytosine nucleotides within the genome encode essential epigenetic information, with methylation (5meC) and hydroxymethylation (5hmC) having received most attention. It has been proposed that the formation of 5hmC is an intermediate in the active demethylation of 5meC. Some reports show that global loss of 5meC in the newly fertilised embryo is accompanied by increased 5hmC, but others have failed to confirm this finding. These analyses have relied on immuno-localization of these modifications. In this study we have established the conditions required for equilibrium binding of antibodies to 5meC and 5hmC in zygotes. Simultaneous detection of these antigens required denaturation of chromatin by acid treatment followed by antigen retrieval by tryptic digestion. Equilibrium binding then required incubation at 4°C for greater than 6 h. These are more demanding conditions than generally reported and resulted in the consistent detection of 5meC and 5hmC in both male and female pronuclei throughout zygotic maturation. No dynamic reciprocal change in the level of 5meC relative to 5hmC was observed. Both 5meC and 5hmC accumulated within the peri-nucleolar regions and this was more pronounced in the male pronucleus. Staining of 5meC was relatively more intense within the cortical and 5hmC in the central regions of pronuclei. The results are not consistent with a role for 5hmC in global demethylation in the zygote. The persistence of both modifications throughout zygotic maturation, and their differing patterns of localization and solvent exposure infer each modification provides its own epigenetic information to the early embryo.
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Contraception in the context of HIV/AIDS: a review.
Afr J Reprod Health
PUBLISHED: 10-18-2011
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Over 50% of the 33.3 million HIV-positive persons are women within the reproductive age group. With increasing availability and use of highly active antiretroviral therapy (HAART), the prognosis, life expectancy and quality of life of infected persons has improved. HIV-positive women, like their uninfected counterparts, may desire to plan pregnancies, limit their families, or avoid pregnancy. The effective use of contraception by HIV-positive clients can contribute significantly to reduction in both sexual and vertical transmission of the virus. HIV-positive clients can use most of the available contraception methods including barrier, hormonal, intrauterine devices and sterilization. However, some antiretroviral drugs interact with hormonal contraceptives with potentials for reduction in efficacy. Dual protection with concomitant use of a more effective contraceptive method and male or female condom to prevent HIV and Sexually transmitted infections (STIs) is the standard. It is necessary to make provision for contraceptive service as part of comprehensive care for the HIV-positive client.
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The use of postmortem computed tomography in the diagnosis of intentional medication overdose.
Forensic Sci Med Pathol
PUBLISHED: 10-17-2011
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The recognition of a well defined basal layer of radio dense material on the postmortem computed tomography (CT) images, in the setting of typical scene findings of an intentional medication overdose and unremarkable external examination of the deceaseds body can, in certain circumstances, permit such cases to be managed without routine full autopsy examination. Preliminary toxicological analysis can be targeted to such cases to provide further supportive evidence of intentional medication overdose. In cases where the scene findings are ambiguous or have been contaminated the postmortem CT images may alert the pathologist of the possibility of overdose in an otherwise apparently natural death. We reviewed 61 cases of documented intentional therapeutic medication overdose and 61 control cases. In the majority of the cases of confirmed intentional therapeutic medication overdose the CT images showed no diagnostic features. However, in many cases a well defined basal layer of radio-opaque material was clearly seen to line the gastric mucosa. The postmortem CT pattern which we believe to be highly suggestive of intentional medication overdose must be differentiated from other causes of increased radio density in the stomach which include CT artefacts.
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Organized outpatient care: stroke prevention clinic referrals are associated with reduced mortality after transient ischemic attack and ischemic stroke.
Stroke
PUBLISHED: 09-15-2011
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Organized inpatient stroke care decreases mortality and morbidity irrespective of patient age, stroke severity, or stroke subtype. Limited information is available on whether organized outpatient care models such as stroke prevention clinics (SPC) improve outcomes after a transient ischemic attack or ischemic stroke. We compared 1-year mortality and stroke readmission in patients with transient ischemic attack or ischemic stroke referred versus not referred to an SPC.
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Efficient generation and cryopreservation of cardiomyocytes derived from human embryonic stem cells.
Regen Med
PUBLISHED: 06-16-2011
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Human embryonic stem cells (hESCs) represent a novel cell source to treat diseases such as heart failure and for use in drug screening. In this study, we aim to promote efficient generation of cardiomyocytes from hESCs by combining the current optimal techniques of controlled growth of undifferentiated cells and specific induction for cardiac differentiation. We also aim to examine whether these methods are scalable and whether the differentiated cells can be cryopreserved.
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Optically controllable photonic structures with zero absorption.
Phys. Rev. Lett.
PUBLISHED: 05-27-2011
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We show the possibility to periodically modulate the refractive index in a homogeneous resonant atomic medium in space or/and time while simultaneously keeping vanishing absorption or gain. Such modulation is based on periodic resonant enhancement of the refractive index, controlled by an external optical field, and opens the way to produce coherently controllable photonic structures. We suggest the possible implementation of the proposed scheme in rare-earth doped crystals with excited state absorption.
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Prevalence and correlates of suicidal behavior among adult female victims of intimate partner violence.
Suicide Life Threat Behav
PUBLISHED: 05-02-2011
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The prevalence and correlates of suicidal threats and attempts among 662 racially and ethnically diverse adult female victims of intimate partner violence (IPV) were studied. One in five women had threatened or attempted suicide during her lifetime. They observed that multiple logistic regression results indicated that women at greater risk of severe or potentially lethal assaults as measured by the Danger Assessment and those who reported having a chronic or disabling illness were more likely to have threatened or attempted suicide. A linear association was found between age and suicide threats/attempts, with younger women having increased odds. Finally, African American IPV victims were less likely to have threatened or attempted suicide as compared to Latina victims. Study implications are discussed.
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Survey of teaching, research and conference experiences of paediatric surgical trainees in Nigeria.
Afr J Paediatr Surg
PUBLISHED: 04-12-2011
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To determine the teaching methods used by residents in paediatric surgery in Nigeria and their exposure to research and conferences.
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The all-age spirometry reference ranges reflect contemporary Australasian spirometry.
Respirology
PUBLISHED: 03-16-2011
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Advances in statistical modelling have allowed the creation of smoothly changing spirometry reference ranges that apply across a wide age range and better define the lower limit of normal. The objective of this study was to assess the agreement of the Stanojevic 2009 all-age reference ranges to contemporary lung function data to verify the appropriateness of this reference for clinical use in Australia and New Zealand.
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Recognition and blocking of innate immunity cells by Candida albicans chitin.
Infect. Immun.
PUBLISHED: 02-28-2011
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Chitin is a skeletal cell wall polysaccharide of the inner cell wall of fungal pathogens. As yet, little about its role during fungus-host immune cell interactions is known. We show here that ultrapurified chitin from Candida albicans cell walls did not stimulate cytokine production directly but blocked the recognition of C. albicans by human peripheral blood mononuclear cells (PBMCs) and murine macrophages, leading to significant reductions in cytokine production. Chitin did not affect the induction of cytokines stimulated by bacterial cells or lipopolysaccharide (LPS), indicating that blocking was not due to steric masking of specific receptors. Toll-like receptor 2 (TLR2), TLR4, and Mincle (the macrophage-inducible C-type lectin) were not required for interactions with chitin. Dectin-1 was required for immune blocking but did not bind chitin directly. Cytokine stimulation was significantly reduced upon stimulation of PBMCs with heat-killed chitin-deficient C. albicans cells but not with live cells. Therefore, chitin is normally not exposed to cells of the innate immune system but is capable of influencing immune recognition by blocking dectin-1-mediated engagement with fungal cell walls.
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Central compartment dissection in thyroid papillary carcinoma.
Ann. Surg.
PUBLISHED: 02-25-2011
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Systematic elective paratracheal dissection for papillary thyroid carcinoma is controversial.
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Centriolar satellites are assembly points for proteins implicated in human ciliopathies, including oral-facial-digital syndrome 1.
J. Cell. Sci.
PUBLISHED: 01-25-2011
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Ciliopathies are caused by mutations in genes encoding proteins required for cilia organization or function. We show through colocalization with PCM-1, that OFD1 (the product of the gene mutated in oral-facial-digital syndrome 1) as well as BBS4 and CEP290 (proteins encoded by other ciliopathy genes) are primarily components of centriolar satellites, the particles surrounding centrosomes and basal bodies. RNA interference experiments reveal that satellite integrity is mutually dependent upon each of these proteins. Upon satellite dispersal, through mitosis or forced microtubule depolymerization, OFD1 and CEP290 remain centrosomal, whereas BBS4 and PCM-1 do not. OFD1 interacts via its fifth coiled-coil motif with the N-terminal coiled-coil domain of PCM-1, which itself interacts via its C-terminal non-coiled-coil region with BBS4. OFD1 localization to satellites requires its N-terminal region, encompassing the LisH motif, whereas expression of OFD1 C-terminal constructs causes PCM-1 and CEP290 mislocalization. Moreover, in embryonic zebrafish, OFD1 and BBS4 functionally synergize, determining morphogenesis. Our observation that satellites are assembly points for several mutually dependent ciliopathy proteins provides a further possible explanation as to why the clinical spectrum of OFD1, Bardet-Biedl and Joubert syndromes overlap. Furthermore, definition of how OFD1 and PCM-1 interact helps explain why different OFD1 mutations lead to clinically variable phenotypes.
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"Buckle" rib fracture: an artifact following cardio-pulmonary resuscitation detected on postmortem CT.
Leg Med (Tokyo)
PUBLISHED: 01-11-2011
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Buckle rib fractures are incomplete fractures involving the inner cortex alone, and are rarely detected on routine chest X-ray or at autopsy. The characteristics of these fractures have not been well evaluated in situ although they are commonly observed on postmortem CT images especially following CPR. The postmortem CT findings in 42 cases showing buckle rib fractures caused by CPR were reviewed. The cause of death in all cases was non-traumatic. The shape, number, location, and distribution of these buckle rib fractures and their relationship to other types of rib fractures were evaluated using a novel oblique axial multiplanar reconstruction technique. Almost all incomplete rib fractures associated with CPR are buckle rib fractures (90.5%). All rib fractures were distributed from the second to ninth ribs with over 95% being within the second to seventh ribs. Buckle rib fractures are dominant in the seventh to ninth ribs and the proportion of buckle rib fractures located in the vicinity of the costochondral junctions increases with the lower ribs. Over 97% of all CPR associated rib fractures are located in the anterior one third of the ribs based on a new measurement method utilizing oblique axial multiplanar reconstruction of the CT data. When recognition of incomplete or buckle rib fractures on postmortem CT is taken into account, detection of symmetry and continuity of rib fractures typically associated with CPR is improved compared with the detection of complete fractures alone. Recognition of buckle rib fractures and their characteristics on postmortem CT is of benefit to the forensic pathologist in evaluating the possibility of CPR and the differentiation of resuscitative artifact from forensically significant visceral injury observed at autopsy.
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Deposition, imaging, and clearance: what remains to be done?
J Aerosol Med Pulm Drug Deliv
PUBLISHED: 12-08-2010
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Deposition and clearance studies are used during product development and in fundamental research. These studies mostly involve radionuclide imaging, but pharmacokinetic methods are also used to assess the amount of drug absorbed through the lungs, which is closely related to lung deposition. Radionuclide imaging may be two-dimensional (gamma scintigraphy or planar imaging), or three-dimensional (single photon emission computed tomography and positron emission tomography). In October 2009, a group of scientists met at the "Thousand Years of Pharmaceutical Aerosols" conference in Reykjavik, Iceland, to discuss future research in key areas of pulmonary drug delivery. This article reports the session on "Deposition, imaging and clearance." The objective was partly to review our current understanding, but more importantly to assess "what remains to be done?" A need to standardize methodology and provide a regulatory framework by which data from radionuclide imaging methods could be compared between centers and used in the drug approval process was recognized. There is also a requirement for novel radiolabeling methods that are more representative of production processes for dry powder inhalers and pressurized metered dose inhalers. A need was identified for studies to aid our understanding of the relationship between clinical effects and regional deposition patterns of inhaled drugs. A robust methodology to assess clearance from small conducting airways should be developed, as a potential biomarker for therapies in cystic fibrosis and other diseases. The mechanisms by which inhaled nanoparticles are removed from the lungs, and the factors on which their removal depends, require further investigation. Last, and by no means least, we need a better understanding of patient-related factors, including how to reduce the variability in pulmonary drug delivery, in order to improve the precision of deposition and clearance measurements.
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Spontaneous acute subdural hematoma complicating arachnoid cyst.
Am J Forensic Med Pathol
PUBLISHED: 11-11-2010
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The overwhelming majority of cases of acute subdural hematoma in the forensic setting occur as a result of head trauma. We report a case of sudden unexpected death in a middle-aged woman with a history of arachnoid cyst who had sudden spontaneous onset of severe headache that was rapidly followed by collapse and death. A postmortem multiple-slice computed tomographic scan showed a large acute subdural hematoma associated with hemorrhage into an arachnoid cyst. Subdural hemorrhage is an uncommon but well-described complication of an arachnoid cyst.
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Association of KRAS p.G13D mutation with outcome in patients with chemotherapy-refractory metastatic colorectal cancer treated with cetuximab.
JAMA
PUBLISHED: 10-28-2010
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Patients with metastatic colorectal cancer who have KRAS codon 12- or KRAS codon 13-mutated tumors are presently excluded from treatment with the anti-epidermal growth factor receptor monoclonal antibody cetuximab.
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Changes in in vivo knee loading with a variable-stiffness intervention shoe correlate with changes in the knee adduction moment.
J. Orthop. Res.
PUBLISHED: 10-26-2010
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External knee adduction moment can be reduced using footwear interventions, but the exact changes in in vivo medial joint loading remain unknown. An instrumented knee replacement was used to assess changes in in vivo medial joint loading in a single patient walking with a variable-stiffness intervention shoe. We hypothesized that during walking with a load modifying variable-stiffness shoe intervention: (1) the first peak knee adduction moment will be reduced compared to a subjects personal shoes; (2) the first peak in vivo medial contact force will be reduced compared to personal shoes; and (3) the reduction in knee adduction moment will be correlated with the reduction in medial contact force. The instrumentation included a motion capture system, force plate, and the instrumented knee prosthesis. The intervention shoe reduced the first peak knee adduction moment (13.3%, p = 0.011) and medial compartment joint contact force (12.3%; p = 0.008) compared to the personal shoe. The change in first peak knee adduction moment was significantly correlated with the change in first peak medial contact force (R(2)?= 0.67, p = 0.007). Thus, for a single subject with a total knee prosthesis the variable-stiffness shoe reduces loading on the affected compartment of the joint. The reductions in the external knee adduction moment are indicative of reductions in in vivo medial compressive force with this intervention.
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Mechanical activation of ?-catenin regulates phenotype in adult murine marrow-derived mesenchymal stem cells.
J. Orthop. Res.
PUBLISHED: 09-28-2010
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Regulation of skeletal remodeling appears to influence the differentiation of multipotent mesenchymal stem cells (MSC) resident in the bone marrow. As murine marrow cultures are contaminated with hematopoietic cells, they are problematic for studying direct effects of mechanical input. Here we use a modified technique to isolate marrow-derived MSC (mdMSC) from adult mice, yielding a population able to differentiate into adipogenic and osteogenic phenotypes that is devoid of hematopoietic cells. In pure mdMSC populations, a daily strain regimen inhibited adipogenic differentiation, suppressing expression of PPAR? and adiponectin. Strain increased ?-catenin and inhibition of adipogenesis required this effect. Under osteogenic conditions, strain activated ?-catenin signaling and increased expression of WISP1 and COX2. mdMSC were also generated from mice lacking caveolin-1, a protein known to sequester ?-catenin: caveolin-1((-/-)) mdMSC exhibited retarded differentiation along both adipogenic and osteogenic lineages but retained mechanical responses that involved ?-catenin activation. Interestingly, caveolin-1((-/-)) mdMSC failed to express bone sialoprotein and did not form mineralized nodules. In summary, mdMSC from adult mice respond to both soluble factors and mechanical input, with mechanical activation of ?-catenin influencing phenotype. As such, these cells offer a useful model for studies of direct mechanical regulation of MSC differentiation and function.
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Common variants at 10 genomic loci influence hemoglobin A?(C) levels via glycemic and nonglycemic pathways.
Nicole Soranzo, Serena Sanna, Eleanor Wheeler, Christian Gieger, Dörte Radke, Josée Dupuis, Nabila Bouatia-Naji, Claudia Langenberg, Inga Prokopenko, Elliot Stolerman, Manjinder S Sandhu, Matthew M Heeney, Joseph M Devaney, Muredach P Reilly, Sally L Ricketts, Alexandre F R Stewart, Benjamin F Voight, Christina Willenborg, Benjamin Wright, David Altshuler, Dan Arking, Beverley Balkau, Daniel Barnes, Eric Boerwinkle, Bernhard Böhm, Amélie Bonnefond, Lori L Bonnycastle, Dorret I Boomsma, Stefan R Bornstein, Yvonne Böttcher, Suzannah Bumpstead, Mary Susan Burnett-Miller, Harry Campbell, Antonio Cao, John Chambers, Robert Clark, Francis S Collins, Josef Coresh, Eco J C de Geus, Mariano Dei, Panos Deloukas, Angela Döring, Josephine M Egan, Roberto Elosua, Luigi Ferrucci, Nita Forouhi, Caroline S Fox, Christopher Franklin, Maria Grazia Franzosi, Sophie Gallina, Anuj Goel, Jurgen Graessler, Harald Grallert, Andreas Greinacher, David Hadley, Alistair Hall, Anders Hamsten, Caroline Hayward, Simon Heath, Christian Herder, Georg Homuth, Jouke-Jan Hottenga, Rachel Hunter-Merrill, Thomas Illig, Anne U Jackson, Antti Jula, Marcus Kleber, Christopher W Knouff, Augustine Kong, Jaspal Kooner, Anna Köttgen, Peter Kovacs, Knut Krohn, Brigitte Kühnel, Johanna Kuusisto, Markku Laakso, Mark Lathrop, Cécile Lecoeur, Man Li, Mingyao Li, Ruth J F Loos, Jian'an Luan, Valeriya Lyssenko, Reedik Mägi, Patrik K E Magnusson, Anders Malarstig, Massimo Mangino, María Teresa Martínez-Larrad, Winfried März, Wendy L McArdle, Ruth McPherson, Christa Meisinger, Thomas Meitinger, Olle Melander, Karen L Mohlke, Vincent E Mooser, Mario A Morken, Narisu Narisu, David M Nathan, Matthias Nauck, Chris O'Donnell, Konrad Oexle, Nazario Olla, James S Pankow, Felicity Payne, John F Peden, Nancy L Pedersen, Leena Peltonen, Markus Perola, Ozren Polašek, Eleonora Porcu, Daniel J Rader, Wolfgang Rathmann, Samuli Ripatti, Ghislain Rocheleau, Michael Roden, Igor Rudan, Veikko Salomaa, Richa Saxena, David Schlessinger, Heribert Schunkert, Peter Schwarz, Udo Seedorf, Elizabeth Selvin, Manuel Serrano-Ríos, Peter Shrader, Angela Silveira, David Siscovick, Kjioung Song, Timothy D Spector, Kari Stefansson, Valgerdur Steinthorsdottir, David P Strachan, Rona Strawbridge, Michael Stumvoll, Ida Surakka, Amy J Swift, Toshiko Tanaka, Alexander Teumer, Gudmar Thorleifsson, Unnur Thorsteinsdottir, Anke Tönjes, Gianluca Usala, Veronique Vitart, Henry Völzke, Henri Wallaschofski, Dawn M Waterworth, Hugh Watkins, H-Erich Wichmann, Sarah H Wild, Gonneke Willemsen, Gordon H Williams, James F Wilson, Juliane Winkelmann, Alan F Wright, , Carina Zabena, Jing Hua Zhao, Stephen E Epstein, Jeanette Erdmann, Hakon H Hakonarson, Sekar Kathiresan, Kay-Tee Khaw, Robert Roberts, Nilesh J Samani, Mark D Fleming, Robert Sladek, Goncalo Abecasis, Michael Boehnke, Philippe Froguel, Leif Groop, Mark I McCarthy, W H Linda Kao, Jose C Florez, Manuela Uda, Nicholas J Wareham, Inês Barroso, James B Meigs.
Diabetes
PUBLISHED: 09-21-2010
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Glycated hemoglobin (HbA?(c)), used to monitor and diagnose diabetes, is influenced by average glycemia over a 2- to 3-month period. Genetic factors affecting expression, turnover, and abnormal glycation of hemoglobin could also be associated with increased levels of HbA?(c). We aimed to identify such genetic factors and investigate the extent to which they influence diabetes classification based on HbA?(c) levels.
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Transformation-related protein 53 expression in the early mouse embryo compromises preimplantation embryonic development by preventing the formation of a proliferating inner cell mass.
Biol. Reprod.
PUBLISHED: 08-25-2010
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The developmental viability of the preimplantation embryo requires the successful formation of a cluster of pluripotent stem cells called the inner cell mass. Development is variably compromised by a range of exogenous stressors (including their production by assisted reproductive technologies). Inbred C57BL/6 strain embryos are particularly susceptible to the stresses associated with embryo culture, whereas hybrid embryos are more resistant, and this is accounted for in part by the overexpression of transformation-related protein 53 in cultured inbred embryos compared with similarly treated hybrid embryos or embryos not subjected to culture. We show here that this loss of viability is a consequence of the Trp53-dependent reduction in the capacity of blastocysts to form a proliferating inner cell mass. Formation of the trophectodermal line was not adversely affected by these stresses.
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MIS416, a non-toxic microparticle adjuvant derived from Propionibacterium acnes comprising immunostimulatory muramyl dipeptide and bacterial DNA promotes cross-priming and Th1 immunity.
Vaccine
PUBLISHED: 08-18-2010
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Propionibacterium acnes was modified using biochemical extraction methods generating a suspension of microparticles (MIS416) comprising a minimal cell wall skeleton rich in immunostimulatory crosslinked muramyl dipeptide repeats and native bacterial DNA fragments, each which have known adjuvant activity. In vitro studies demonstrated that MIS416 was readily internalized by human myeloid and plasmacytoid DC inducing cytokine secretion and cell activation/maturation. Vaccination studies in mice using OVA as a model antigen demonstrated that MIS416 acts as a Th1 adjuvant, promoting cross-priming of cytotoxic CD8(+) T cell responses and enhanced anti-tumour immunity. Covalent attachment of OVA to MIS416 enabling simultaneous delivery of antigen and adjuvant to the antigen presentation system resulted in a dose-sparing vaccine formulation. Preclinical GLP toxicology studies demonstrated that MIS416 has a favorable safety profile in mouse and rabbit supporting its use in human vaccine formulations.
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Histone deacetylase inhibition attenuates cell growth with associated telomerase inhibition in high-grade childhood brain tumor cells.
Mol. Cancer Ther.
PUBLISHED: 07-19-2010
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Aberrant epigenetic regulation of gene expression contributes to tumor initiation and progression. Studies from a plethora of hematologic and solid tumors support the use of histone deacetylase inhibitors (HDACi) as potent anticancer agents. However, the mechanism of HDACi action with respect to the temporal order of induced cellular events is unclear. The present study investigates the anticancer effects of the HDACi trichostatin A in high-grade childhood brain tumor cells. Acute exposure to trichostatin A resulted in marked inhibition of cell proliferation, an increase in the proportion of G(2)-M cells, activation of H2A.X, and subsequent induction of apoptosis in the majority of cell lines. These phenotypic effects were associated with abrogation of telomerase activity and human telomerase reverse transcriptase downregulation in the majority of cell lines. In contrast, no cytotoxicity was observed in primary ependymal cells with respect to cilia function. Thus, inhibition of histone deacetylases leads to antiproliferative and proapoptotic effects in childhood brain tumor cells, likely to involve altered chromatin regulation at the human telomerase reverse transcriptase promoter.
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Ciliated air-liquid cultures as an aid to diagnostic testing of primary ciliary dyskinesia.
Chest
PUBLISHED: 07-08-2010
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The diagnosis of primary ciliary dyskinesia (PCD) can prove difficult because of secondary damage of ciliated tissue.
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Early oncological outcomes of robot-assisted radical prostatectomy for high-grade prostate cancer.
BJU Int.
PUBLISHED: 06-26-2010
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To evaluate the oncological outcomes of patients with specimen Gleason 8 and 9 prostate cancers and to determine factors that predict biochemical recurrence-free survival (BCRFS) after robot-assisted radical prostatectomy (RARP).
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Postmortem computed tomography findings of upper airway obstruction by food.
J. Forensic Sci.
PUBLISHED: 06-25-2010
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This study is a retrospective analysis of 14 cases with food bolus upper airway obstruction as the defined cause of death where both postmortem computed tomography and autopsy were performed. Three groups were defined by the images i.e., Type 1: foreign body situated between the oral cavity and oropharynx, while the epiglottis sits in normal position, Type 2: foreign body situated in the oropharynx just above the epiglottis pushing it posteriorly and obstructing the airway, and Type 3: foreign body obstructing the laryngeal inlet while pushing the epiglottis anteriorly. At the time of autopsy, foreign bodies were detected by pathologists, occasionally in a different position, presumably being dislodged in the act of organ removal especially for the "Type 1" pattern. CT imaging provides accurate interrogation of upper airway bolus obstruction prior to autopsy.
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Characterization of a diverse secretome generated by the mouse preimplantation embryo in vitro.
Reprod. Biol. Endocrinol.
PUBLISHED: 03-30-2010
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This study investigates the suitability of surface-enhanced laser desorption and ionization time-of-flight (SELDI-TOF) and electrospray ionization (ESI) mass spectrometry for analysis of the proteins released by the mouse preimplantation embryo in vitro. SELDI-TOF analysis with CM10 or IMAC30 (but not Q10) protein chips detected a protein peak at m/z approximately 8570 released by both C57BL6 and hybrid embryos. No other peaks unique to the presence of the embryo were identified with this method. ESI mass spectrometry of tryptic digests of embryo-conditioned media identified a total of 20 proteins released during development from the zygote to blastocyst stage. Four proteins were expressed in at least 7 out of 8 cultures tested, one of these (lactate dehydrogenase B) was in all cultures. A further five proteins were in at least half of the cultures and 11 more proteins were in at least one culture. The expression of two of these proteins is essential for preimplantation embryo development (NLR family, pyrin domain containing 5 and peptidyl arginine deiminase, type VI). A further four proteins detected have roles in redox regulation of cells, and three others are capable of inducing post-translational modifications of proteins. This study shows the feasibility of ESI mass spectrometry for identifying the proteins secreted by the preimplantation embryo in vitro. This analysis identifies a range of targets that now require detailed functional analysis to assess whether their release by the embryo is an important property of early embryo development.
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Reversible renal impairment caused by thyroid disease.
Scand. J. Urol. Nephrol.
PUBLISHED: 03-05-2010
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Renal impairment is a common finding in clinical practice and is increasingly recognized with the routine reporting of estimated glomerular filtration rates. Clinical assessment is essential to determine which of the many possible investigations are appropriate. Thyroid hormones regulate many cellular functions, and abnormalities of the active thyroid hormones, thyroxine (T(4)) and tri-iodothyronine (T(3)), can influence serum creatinine levels. Evaluation of thyroid function is easily overlooked, but important in this context, as hypothyroidism is common and can cause renal impairment, which is typically reversible. Renal dysfunction may also be more frequent in hyperthyroidism than is recognized. This report describe how a dramatic elevation in serum creatinine paralleled the development of hyperthyroidism, with a return of the creatinine to normal following treatment of the hyperthyroid state.
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Linaclotide improves abdominal pain and bowel habits in a phase IIb study of patients with irritable bowel syndrome with constipation.
Gastroenterology
PUBLISHED: 02-12-2010
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Linaclotide, a minimally absorbed, 14-amino acid peptide agonist of guanylate cyclase-C, has shown benefit in a proof-of-concept study for the treatment of patients with irritable bowel syndrome (IBS) with constipation (IBS-C). We assessed the efficacy and safety of linaclotide at a daily dose range of 75-600 ?g in IBS-C.
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Understanding delay in accessing specialist emergency eye care in a developing country: eye trauma in Tanzania.
Ophthalmic Epidemiol
PUBLISHED: 02-06-2010
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To determine the extent and reasons for delay in accessing specialist eye care following a significant eye injury.
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Differences in tibial rotation during walking in ACL reconstructed and healthy contralateral knees.
J Biomech
PUBLISHED: 02-05-2010
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This study tested the hypotheses that in patients with a successful anterior cruciate ligament (ACL) reconstruction, the internal-external rotation, varus-valgus, and knee flexion position of reconstructed knees would be different from uninjured contralateral knees during walking. Twenty-six subjects with unilateral ACL reconstructions (avg 31 years, 1.7 m, 68 kg, 15 female, 24 months past reconstruction) and no other history of serious lower limb injury walked at a self-selected speed in the gait laboratory, with the uninjured contralateral knee as a matched control. Kinematic measurements of tibiofemoral motion were made using a previously-described point-cluster technique. Repeated-measures ANOVA (alpha=0.017) was used to compare ACL-reconstructed knees to their contralateral knees at four distinct points during the stance phase of walking. An offset towards external tibial rotation in ACL-reconstructed knees was maintained over all time points (95%CI 2.3+/-1.3 degrees ). Twenty-two out of twenty-six individuals experienced an average external tibial rotation offset throughout stance phase. Varus-valgus rotation and knee flexion were not significantly different between reconstructed and contralateral knees. These findings show that differences in tibial rotation during walking exist in ACL reconstructed knees compared to healthy contralateral knees, providing a potential explanation why these patients are at higher risk of knee osteoarthritis in the long-term.
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The efficacy of cognitive-behavioral therapy for insomnia in patients with chronic pain.
Sleep Med.
PUBLISHED: 02-04-2010
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To assess the efficacy of cognitive-behavioral therapy for insomnia (CBT-I) in patients with non-malignant chronic pain.
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Pathogenicity islands PAPI-1 and PAPI-2 contribute individually and synergistically to the virulence of Pseudomonas aeruginosa strain PA14.
Infect. Immun.
PUBLISHED: 02-01-2010
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Pseudomonas aeruginosa is a leading cause of hospital-acquired pneumonia and severe chronic lung infections in cystic fibrosis patients. The reference strains PA14 and PAO1 have been studied extensively, revealing that PA14 is more virulent than PAO1 in diverse infection models. Among other factors, this may be due to two pathogenicity islands, PAPI-1 and PAPI-2, both present in PA14 but not in PAO1. We compared the global contributions to virulence of PAPI-1 and PAPI-2, rather than that of individual island-borne genes, using murine models of acute pneumonia and bacteremia. Three isogenic island-minus mutants (PAPI-1-minus, PAPI-2-minus, and PAPI-1-minus, PAPI-2-minus mutants) were compared with the wild-type parent strain PA14 and with PAO1. Our results showed that both islands contributed significantly to the virulence of PA14 in acute pneumonia and bacteremia models. However, in contrast to the results for the bacteremia model, where each island was found to contribute individually, loss of the 108-kb PAPI-1 island alone was insufficient to measurably attenuate the mutant in the acute pneumonia model. Nevertheless, the double mutant was substantially more attenuated, and exhibited a lesser degree of virulence, than even PAO1 in the acute pneumonia model. In particular, its ability to disseminate from the lungs to the bloodstream was markedly inhibited. We conclude that both PAPI-1 and PAPI-2 contribute directly and synergistically in a major way to the virulence of PA14, and we suggest that analysis of island-minus strains may be a more appropriate way than individual gene knockouts to assess the contributions to virulence of large, horizontally acquired segments of DNA.
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The behaviour of both Listeria monocytogenes and rat ciliated ependymal cells is altered during their co-culture.
PLoS ONE
PUBLISHED: 01-18-2010
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Ciliated ependymal cells line the cerebral ventricles and aqueducts separating the infected CSF from the brain parenchyma in meningitis.
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Single nucleotide polymorphism analysis of the NKG2D ligand cluster on the long arm of chromosome 6: Extensive polymorphisms and evidence of diversity between human populations.
Hum. Immunol.
PUBLISHED: 01-04-2010
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NKG2D is an important activating receptor on NK cells and T-cells and has a diverse panel of ligands (NKG2DL) which include the ULBP and RAET1 proteins. Several NKG2DL exhibit a considerable degree of genetic polymorphism, and although the functional significance of such allelic variation remains unclear, genetic variants have been implicated in susceptibility to infection and auto-immune disease. We used sequence-specific primer polymerase chain reaction to determine the frequency of 25 single nucleotide polymorphisms (SNPs) in the promoter and coding regions of genes of the RAET1/ULBP cluster in 223 Euro-Caucasoid, 60 Afro-Caribbean, and 52 Indo-Asian individuals to determine NKG2DL allele and haplotype frequencies within these populations. We show marked differences in the frequency of NKG2DL SNPs and haplotypes among the three ethnic groups, and certain haplotypes were observed almost exclusively in Afro-Caribbean compared with the Euro-Caucasoid and Indo-Asian populations. Interestingly, variation was focused within the RAET1E (ULBP4), RAET1L, and ULBP3 genes, whereas the ULBP1, ULBP2 and RAET1G (ULBP5) genes were highly conserved. These findings suggest that individual NKG2DL alleles have been subject to divergent selective pressures during the migration of Homo sapiens. This information will be of importance in understanding the biology and clinical significance of NKG2DL polymorphism.
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Association between disease-free survival and overall survival when survival is prolonged after recurrence in patients receiving cytotoxic adjuvant therapy for colon cancer: simulations based on the 20,800 patient ACCENT data set.
J. Clin. Oncol.
PUBLISHED: 12-14-2009
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We previously validated disease-free survival (DFS) as a surrogate for overall survival (OS) in fluorouracil-based adjuvant colon cancer clinical trials. New therapies have extended survival after recurrence from 1 to approximately 2 years. We examined the possible impact of this improvement on the DFS/OS association.
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Intimate partner violence: development of a brief risk assessment for the emergency department.
Acad Emerg Med
PUBLISHED: 12-07-2009
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Women assaulted by intimate partners are frequently patients in emergency departments (EDs). Many victims and health care providers fail to take into account the potential risks of repeat partner violence. The objective of this study was to use data from a larger study of domestic violence risk assessment methods to develop a brief assessment for acute care settings to identify victims at highest risk for suffering severe injury or potentially lethal assault by an intimate partner or former partner.
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Diagnostic testing of patients suspected of primary ciliary dyskinesia.
Am. J. Respir. Crit. Care Med.
PUBLISHED: 11-12-2009
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Electron microscopy (EM) of ciliated epithelium is widely used to diagnose primary ciliary dyskinesia (PCD). Ciliary beat frequency (CBF) has been used to screen samples to determine whether EM is indicated. Beat pattern analysis has been advocated as an additional diagnostic test. Neither has been subject to formal review.
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The platelet receptor CLEC-2 is active as a dimer.
Biochemistry
PUBLISHED: 10-15-2009
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The platelet receptor CLEC-2 binds to the snake venom toxin rhodocytin and the tumor cell surface protein podoplanin. Binding of either of these ligands promotes phosphorylation of a single tyrosine residue in the YXXL motif in the intracellular domain of CLEC-2. Phosphorylation of this tyrosine initiates binding of spleen tyrosine kinase (Syk) and triggers further downstream signaling events and ultimately potent platelet activation and aggregation. However, it is unclear how a single YXXL motif can interact efficiently with Syk, which usually recognizes two tandem YXXL repeats presented as an immunoreceptor tyrosine-based activation motif (ITAM). Using bioluminescence resonance energy transfer, coimmunopreciptitation, recombinant protein expression and analytical gel filtration chromatography, surface plasmon resonance, Western blotting, multiangle light scattering (MALS), and analytical ultracentrifugation, we show that CLEC-2 exists as a non-disulfide-linked homodimer which could allow each Syk molecule to interact with two YXXL motifs, one from each CLEC-2 monomer.
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Protective effects of dietary antioxidants on proton total-body irradiation-mediated hematopoietic cell and animal survival.
Radiat. Res.
PUBLISHED: 07-28-2009
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Abstract Dietary antioxidants have radioprotective effects after gamma-radiation exposure that limit hematopoietic cell depletion and improve animal survival. The purpose of this study was to determine whether a dietary supplement consisting of l-selenomethionine, vitamin C, vitamin E succinate, alpha-lipoic acid and N-acetyl cysteine could improve survival of mice after proton total-body irradiation (TBI). Antioxidants significantly increased 30-day survival of mice only when given after irradiation at a dose less than the calculated LD(50/30); for these data, the dose-modifying factor (DMF) was 1.6. Pretreatment of animals with antioxidants resulted in significantly higher serum total white blood cell, polymorphonuclear cell and lymphocyte cell counts at 4 h after 1 Gy but not 7.2 Gy proton TBI. Antioxidants significantly modulated plasma levels of the hematopoietic cytokines Flt-3L and TGFbeta1 and increased bone marrow cell counts and spleen mass after TBI. Maintenance of the antioxidant diet resulted in improved recovery of peripheral leukocytes and platelets after sublethal and potentially lethal TBI. Taken together, oral supplementation with antioxidants appears to be an effective approach for radioprotection of hematopoietic cells and improvement of animal survival after proton TBI.
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Making reliable decisions in the study of wildlife diseases: using hypothesis tests, statistical power, and observed effects.
J. Wildl. Dis.
PUBLISHED: 07-21-2009
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The increasing importance of wildlife diseases in conservation efforts places an additional importance on research study design, data analysis, and interpretation. In this paper, we explore the design and analysis of wildlife disease data with regard to hypothesis testing, statistical power, sample sizes, the relative costs of type I versus type II errors, and effect size. To illustrate these ideas, we conducted a literature review of the Journal of Wildlife Diseases (JWD), ran computer simulations that estimate type II error rates for statistical techniques commonly used in JWD, and reanalyzed previously published data on disease prevalence. Many studies published in JWD used chi-squared analysis on prevalence data, but only 19% reported estimates of the observed effect size. Furthermore, 10% of studies had pooled sample sizes < or =40, and many had potentially high costs of type II relative to type I errors. Our computer simulations suggest that many articles published in JWD lack sufficient statistical power, and this, coupled with our findings that many studies often ignore high costs of type II errors, argues for increased attention to statistical power. Finally, our data reanalysis shows how the presentation of observed effect sizes could allow a better assessment of the biologic significance of findings reported in JWD. We conclude with some general guidelines to assist wildlife disease researchers in the design of future studies and the statistical analysis of their data.
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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.

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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.