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Find video protocols related to scientific articles indexed in Pubmed.
Australian enterococcal sepsis outcome progamme, 2011.
Commun Dis Intell Q Rep
PUBLISHED: 11-14-2014
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From 1 January to 31 December 2011, 29 institutions around Australia participated in the Australian Enterococcal Sepsis Outcome Programme (AESOP). The aim of AESOP 2011 was to determine the proportion of enterococcal bacteraemia isolates in Australia that are antimicrobial resistant, with particular emphasis on susceptibility to ampicillin and the glycopeptides, and to characterise the molecular epidemiology of the Enterococcus faecalis and E. faecium isolates. Of the 1,079 unique episodes of bacteraemia investigated, 95.8% were caused by either E. faecalis (61.0%) or E. faecium (34.8%). Ampicillin resistance was detected in 90.4% of E. faecium but not detected in E. faecalis. Using Clinical and Laboratory Standards Institute breakpoints (CLSI), vancomycin non-susceptibility was reported in 0.6% and 31.4% of E. faecalis and E. faecium respectively and was predominately due to the acquisition of the vanB operon. Approximately 1 in 6 vanB E. faecium isolates however, had an minimum inhibitory concentration at or below the CLSI vancomycin susceptible breakpoint of ? 4 mg/L. Overall, 37% of E. faecium harboured vanA or vanB genes. Although molecular typing identified 126 E. faecalis pulsed-field gel electrophoresis (PFGE) pulsotypes, more than 50% belonged to 2 pulsotypes that were isolated across Australia. E. faecium consisted of 73 PFGE pulsotypes from which 43 multilocus sequence types were identified. Almost 90% of the E. faecium were identified as clonal complex 17 clones, of which approximately half were characterised as sequence type 203, which was isolated Australia-wide. In conclusion, the AESOP 2011 has shown that although polyclonal, enterococcal bacteraemias in Australia are frequently caused by ampicillin-resistant vanB E. faecium.
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Reduction of Diffusive Contaminant Emissions from a Dissolved Source in a Lower Permeability Layer by Sodium Persulfate Treatment.
Environ. Sci. Technol.
PUBLISHED: 11-12-2014
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Residual contamination contained in lower permeability zones is difficult to remediate and can, through diffusive emissions to adjacent higher permeability zones, result in long-term impacts to groundwater. This work investigated the effectiveness of oxidant delivery for reducing diffusive emissions from lower permeability zones. The experiment was conducted in a 1.2 m tall x 1.2 m wide x 6 cm thick tank containing two soil layers having three orders of magnitude contrast in hydraulic conductivity. The lower permeability layer initially contained dissolved methyl tert-butyl ether (MTBE), benzene, toluene, ethylbenzene, and p-xylenes (BTEX). The treatment involved delivery of 10% w/w non-activated sodium persulfate (Na2S2O8) solution to the high permeability layer for 14 days. The subsequent diffusion into the lower permeability layer and contaminant emission response were monitored for about 240 days. The S2O8(2-) diffused about 14 cm at 1% w/w into the lower permeability layer during the 14 day delivery, and continued diffusing deeper into the layer as well as back toward the higher-lower permeability interface after delivery ceased. Over 209 days the S2O8(2-) diffused 60 cm into the lower permeability layer, the BTEX mass and emission rate were reduced by 95-99%, and the MTBE emission rate was reduced by 63%. The overall treatment efficiency was about 60 - 110 g- S2O8(2-)-delivered/g-hydrocarbon oxidized, with a significant fraction of the oxidant delivered likely lost by back-diffusion and not involved in hydrocarbon destruction.
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In vitro assessment of human islet vulnerability to instant blood mediated inflammatory reaction (IBMIR) and its use to demonstrate a beneficial effect of tissue culture.
Cell Transplant
PUBLISHED: 11-07-2014
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Culture of human pancreatic islets is now routinely carried out prior to clinical islet allotransplantation, using conditions that have been developed empirically. One of the major causes of early islet destruction after transplantation is the process termed instant blood mediated inflammatory reaction (IBMIR). The aim of this study was to develop in vitro methods to investigate IBMIR and apply them to the culture conditions used routinely in our human islet isolation laboratory. Freshly isolated or pre-cultured (24 h, 48 h) human islets were incubated in either ABO compatible allogeneic human blood or Hank's buffered salt solution (HBSS) for 1 h at 37°C. Tissue factor (TF) expression and leukocyte migration were assessed by light microscopy. TF was also quantified by ELISA. To assess ? cell function, glucose stimulated insulin secretion (GSIS) assay was carried out. The extent of islet ? cell damage was quantified using a proinsulin assay. Islets cultured for 24 h had higher GSIS when compared to freshly isolated or 48 h pre-cultured islets. Freshly isolated islets had significantly higher TF content than 24 h and 48 h pre-cultured islets. Incubation of freshly isolated human islets in allogeneic human blood released 6.5 fold higher level of proinsulin in comparison to freshly isolated human islets in HBSS. The high level of proinsulin released was significantly attenuated when pre-cultured islets (24 h or 48 h) were exposed to fresh blood. Histological examination of fresh islets in blood clot showed that some islets were fragmented, showing signs of extra-islet insulin leakage and extensive neutrophil infiltration and necrosis. These features were markedly reduced when the islets were cultured for 24 h. These results suggest that our standard 24 h islet culture is markedly beneficial in attenuating IBMIR, as evidenced by increased GSIS, lower content of TF, decrease islet fragmentation and proinsulin release.
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Outcomes of Prenatally Diagnosed Lung Lesions in Multigestational Pregnancies.
Fetal. Diagn. Ther.
PUBLISHED: 11-05-2014
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Background: The outcomes of prenatally diagnosed lung lesions in the context of multigestational pregnancies are unknown. Methods: Of 960 fetal lung lesion cases evaluated at a single tertiary center over 16 years, 30 occurred in multigestational pregnancies. We reviewed this series to aid in prenatal counseling of affected families and to provide prognostic information for decision making. Pre- and postnatal clinical characteristics were gathered for these pregnancies, and the morbidity and mortality were determined for both affected and normal fetuses, whether twins or triplets. Results: Mortality was found to be 3/30 (10%) for affected fetuses, and morbidity in normal co-twins was consistent with the degree of prematurity. No morbidity was seen in co-twins born at or after 36 weeks of gestation. Median gestational age at delivery was 35 5/7 weeks. Conclusions: Outcomes for the affected fetus correlate with the size and pathophysiologic consequences of the lesion and are not worse than previously reported outcomes for similar lesions in singleton pregnancies, while morbidity in the normal co-twin is consistent with prematurity related to the fetal age of the multiple gestation at delivery, irrespective of the fetal lung lesion. © 2014 S. Karger AG, Basel.
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Alveolar Bone Loss is Associated with Circulating Anti-Citrullinated Protein Antibody (ACPA) in Rheumatoid Arthritis Patients.
J. Periodontol.
PUBLISHED: 10-10-2014
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Background: To examine: 1) alveolar bone loss (ABL), a hallmark of periodontitis, in anti-citrullinated protein antibody (ACPA)-positive rheumatoid arthritis (RA) patients versus osteoarthritis controls and 2) the association of ABL with RA disease activity and ACPA concentrations, including multiple antigen-specific ACPA. Methods: This multicenter case-control study included 617 patients diagnosed with RA (n=287) or osteoarthritis (n=330). Panoramic radiographs were taken; patients were categorized into low, moderate or high tertiles based on mean percentage ABL. Serum ACPA was measured using second-generation anti-cyclic citrullinated peptide ELISA and by BioPlex platform to assess distinct antigen-specific ACPA. A generalized linear mixed model for binary data was used to compare stratified ABL in RA versus osteoarthritis patients. Associations of moderate and high ABL (versus low) with RA disease activity and severity measures were examined using multivariate regression. Antigen-specific ACPA responses were compared among ABL tertiles using Significance Analysis of Microarrays. Results: ACPA-positive RA patients had a significantly higher mean percentage of sites with ABL greater than 20% compared to osteoarthritis controls (p=0.03). Following multivariate adjustment, greater ABL was significantly associated with higher ACPA concentration (p=0.004), DAS-28-CRP (p=0.023), health assessment questionnaire disability (p=0.05), tender joint count (p=0.02) and joint space narrowing scores (p=0.05) among RA patients. ACPAs targeting citrullinated vimentin and histone were significantly higher in moderate and high ABL groups versus low, regardless of smoking status (q<0.1%). Conclusions: Greater ABL was associated with higher ACPA, consistent with findings at articular sites. ACPA targeting could provide novel insight into important linkages between RA and periodontitis.
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HMG-coenzyme A reductase inhibition, type 2 diabetes, and bodyweight: evidence from genetic analysis and randomised trials.
Daniel I Swerdlow, David Preiss, Karoline B Kuchenbaecker, Michael V Holmes, Jorgen E L Engmann, Tina Shah, Reecha Sofat, Stefan Stender, Paul C D Johnson, Robert A Scott, Maarten Leusink, Niek Verweij, Stephen J Sharp, Yiran Guo, Claudia Giambartolomei, Christina Chung, Anne Peasey, Antoinette Amuzu, KaWah Li, Jutta Palmen, Philip Howard, Jackie A Cooper, Fotios Drenos, Yun R Li, Gordon Lowe, John Gallacher, Marlene C W Stewart, Ioanna Tzoulaki, Sarah G Buxbaum, Daphne L van der A, Nita G Forouhi, N Charlotte Onland-Moret, Yvonne T van der Schouw, Renate B Schnabel, Jaroslav A Hubacek, Růžena Kubinova, Miglė Bacevičienė, Abdonas Tamosiunas, Andrzej Pająk, Romanvan Topor-Madry, Urszula Stepaniak, Sofia Malyutina, Damiano Baldassarre, Bengt Sennblad, Elena Tremoli, Ulf de Faire, Fabrizio Veglia, Ian Ford, J Wouter Jukema, Rudi G J Westendorp, Gert Jan de Borst, Pim A de Jong, Ale Algra, Wilko Spiering, Anke H Maitland-van der Zee, Olaf H Klungel, Anthonius de Boer, Pieter A Doevendans, Charles B Eaton, Jennifer G Robinson, David Duggan, , John Kjekshus, John R Downs, Antonio M Gotto, Anthony C Keech, Roberto Marchioli, Gianni Tognoni, Peter S Sever, Neil R Poulter, David D Waters, Terje R Pedersen, Pierre Amarenco, Haruo Nakamura, John J V McMurray, James D Lewsey, Daniel I Chasman, Paul M Ridker, Aldo P Maggioni, Luigi Tavazzi, Kausik K Ray, Sreenivasa Rao Kondapally Seshasai, JoAnn E Manson, Jackie F Price, Peter H Whincup, Richard W Morris, Debbie A Lawlor, George Davey Smith, Yoav Ben-Shlomo, Pamela J Schreiner, Myriam Fornage, David S Siscovick, Mary Cushman, Meena Kumari, Nick J Wareham, W M Monique Verschuren, Susan Redline, Sanjay R Patel, John C Whittaker, Anders Hamsten, Joseph A Delaney, Caroline Dale, Tom R Gaunt, Andrew Wong, Diana Kuh, Rebecca Hardy, Sekar Kathiresan, Berta A Castillo, Pim van der Harst, Eric J Brunner, Anne Tybjaerg-Hansen, Michael G Marmot, Ronald M Krauss, Michael Tsai, Josef Coresh, Ronald C Hoogeveen, Bruce M Psaty, Leslie A Lange, Hakon Hakonarson, Frank Dudbridge, Steve E Humphries, Philippa J Talmud, Mika Kivimäki, Nicholas J Timpson, Claudia Langenberg, Folkert W Asselbergs, Mikhail Voevoda, Martin Bobak, Hynek Pikhart, James G Wilson, Alex P Reiner, Brendan J Keating, Aroon D Hingorani, Naveed Sattar.
Lancet
PUBLISHED: 09-29-2014
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Statins increase the risk of new-onset type 2 diabetes mellitus. We aimed to assess whether this increase in risk is a consequence of inhibition of 3-hydroxy-3-methylglutaryl-CoA reductase (HMGCR), the intended drug target.
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Personalised physician learning intervention to improve hypertension and lipid control: randomised trial comparing two methods of physician profiling.
BMJ Qual Saf
PUBLISHED: 09-16-2014
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To assess the impact of personalised physician learning (PPL) interventions using simulated learning cases on control of hypertension and dyslipidaemia in primary care settings.
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Association between parent-infant interactions in infancy and disruptive behaviour disorders at age seven: a nested, case-control ALSPAC study.
BMC Pediatr
PUBLISHED: 09-06-2014
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Effective early intervention to prevent oppositional/conduct disorders requires early identification of children at risk. Patterns of parent-child interaction may predict oppositional/conduct disorders but large community-based prospective studies are needed to evaluate this possibility.
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Pharmacokinetics of short versus extended infusion meropenem dosing in critically ill patients: a pilot study.
Crit Care Resusc
PUBLISHED: 08-28-2014
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To test whether a prolonged 3-hour infusion of meropenem 500mg achieves an equivalent proportion of time above the minimal inhibitory concentration (MIC) (%TMIC) to that of meropenem 1000mg given over 30 minutes.
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Outcomes at one-year post anastomosis from a national cohort of infants with oesophageal atresia.
PLoS ONE
PUBLISHED: 08-25-2014
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We aimed to provide a contemporaneous assessment of outcomes at one-year post oesophageal atresia/tracheoesophageal fistula (OA-TOF) repair, focussing particularly on post-operative complications. It is generally accepted that oesophageal stricture is the most common complication and causes significant morbidity. We also aimed to assess the efficacy of prophylactic anti-reflux medication (PARM) in reducing stricture formation.
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Live simian immunodeficiency virus vaccine correlate of protection: immune complex-inhibitory Fc receptor interactions that reduce target cell availability.
J. Immunol.
PUBLISHED: 08-20-2014
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Principles to guide design of an effective vaccine against HIV are greatly needed, particularly to protect women in the pandemic's epicenter in Africa. We have been seeking these principles by identifying correlates of the robust protection associated with SIVmac239?nef vaccination in the SIV-rhesus macaque animal model of HIV-1 transmission to women. We identified one correlate of SIVmac239?nef protection against vaginal challenge as a resident mucosal system for SIV-gp41 trimer Ab production and neonatal FcR-mediated concentration of these Abs on the path of virus entry to inhibit establishment of infected founder populations at the portal of entry. In this study, we identify blocking CD4(+) T cell recruitment to thereby inhibit local expansion of infected founder populations as a second correlate of protection. Virus-specific immune complex interactions with the inhibitory Fc?RIIb receptor in the epithelium lining the cervix initiate expression of genes that block recruitment of target cells to fuel local expansion. Immune complex-Fc?RIIb receptor interactions at mucosal frontlines to dampen the innate immune response to vaginal challenge could be a potentially general mechanism for the mucosal immune system to sense and modulate the response to a previously encountered pathogen. Designing vaccines to provide protection without eliciting these transmission-promoting innate responses could contribute to developing an effective HIV-1 vaccine.
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Live simian immunodeficiency virus vaccine correlate of protection: local antibody production and concentration on the path of virus entry.
J. Immunol.
PUBLISHED: 08-18-2014
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We sought design principles for a vaccine to prevent HIV transmission to women by identifying correlates of protection conferred by a highly effective live attenuated SIV vaccine in the rhesus macaque animal model. We show that SIVmac239?nef vaccination recruits plasma cells and induces ectopic lymphoid follicle formation beneath the mucosal epithelium in the rhesus macaque female reproductive tract. The plasma cells and ectopic follicles produce IgG Abs reactive with viral envelope glycoprotein gp41 trimers, and these Abs are concentrated on the path of virus entry by the neonatal FcR in cervical reserve epithelium and in vaginal epithelium. This local Ab production and delivery system correlated spatially and temporally with the maturation of local protection against high-dose pathogenic SIV vaginal challenge. Thus, designing vaccines to elicit production and concentration of Abs at mucosal frontlines could aid in the development of an effective vaccine to protect women against HIV-1.
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Combining organophosphate-treated wall linings and long-lasting insecticidal nets fails to provide additional control over long-lasting insecticidal nets alone against multiple insecticide-resistant Anopheles gambiae in Côte d'Ivoire: an experimental hut trial.
Malar. J.
PUBLISHED: 07-22-2014
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Insecticide-treated wall lining (ITWL) is a new concept in malaria vector control. Some Anopheles gambiae populations in West Africa have developed resistance to all the main classes of insecticides. It needs to be demonstrated whether vector control can be improved or resistance managed when non-pyrethroid ITWL is used alone or together with long-lasting insecticidal nets (LLINs) against multiple insecticide-resistant vector populations.
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Predictors of positive and negative parenting behaviours: evidence from the ALSPAC cohort.
BMC Pediatr
PUBLISHED: 07-22-2014
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This study aimed to establish the predictors of positive and negative parenting behaviours in a United Kingdom population. The majority of previous research has focused on specific risk factors and has used a variety of outcome measures. This study used a single assessment of parenting behaviours and started with a wide range of potential pre- and post-natal variables; such an approach might be used to identify families who might benefit from parenting interventions.
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Genetic and molecular predictors of high vancomycin MIC in Staphylococcus aureus bacteremia isolates.
J. Clin. Microbiol.
PUBLISHED: 07-16-2014
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An elevated vancomycin MIC is associated with poor outcomes in Staphylococcus aureus bacteremia (SAB) and is reported in patients with methicillin-susceptible S. aureus (MSSA) bacteremia in the absence of vancomycin treatment. Here, using DNA microarray and phenotype analysis, we investigated the genetic predictors and accessory gene regulator (agr) function and their relationship with elevated vancomycin MIC using blood culture isolates from a multicenter binational cohort of patients with SAB. Specific clonal complexes were associated with elevated (clonal complex 8 [CC8] [P < 0.001]) or low (CC22 [P < 0.001], CC88 [P < 0.001], and CC188 [P = 0.002]) vancomycin MIC. agr dysfunction (P = 0.014) or agr genotype II (P = 0.043) were also associated with an elevated vancomycin MIC. Specific resistance and virulence genes were also linked to an elevated vancomycin MIC, including blaZ (P = 0.002), sea (P < 0.001), clfA (P < 0.001), splA (P = 0.001), and the arginine catabolic mobile element (ACME) locus (P = 0.02). These data suggest that inherent organism characteristics may explain the link between elevated vancomycin MICs and poor outcomes in patients with SAB, regardless of the antibiotic treatment received. A consideration of clonal specificity should be included in future research when attempting to ascertain treatment effects or clinical outcomes.
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Educating Resident Physicians Using Virtual Case-Based Simulation Improves Diabetes Management: A Randomized Controlled Trial.
Acad Med
PUBLISHED: 07-10-2014
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To test a virtual case-based Simulated Diabetes Education intervention (SimDE) developed to teach primary care residents how to manage diabetes.
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Evaluation of the Moisture Prediction Capability of Near-Infrared and Attenuated Total Reflectance Fourier Transform Infrared Spectroscopy Using Superdisintegrants as Model Compounds.
J Pharm Sci
PUBLISHED: 07-01-2014
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The superdisintegrants (SDs) moisture content measurement by near-infrared (NIR) spectroscopy and attenuated total reflectance Fourier transform infrared (ATR-FTIR) spectroscopy has been evaluated against thermogravimetric analysis as a reference method. SDs with varying moisture content were used to build calibration and independent model verification data sets. Calibration models were developed based on the water-specific NIR and ATR-FTIR spectral regions using partial least-square regression methods. Because of the NIR water low molar absorptivity, NIR spectroscopy handled higher moisture content (?81%, w/w) than ATR-FTIR (?25%, w/w). A two-way ANOVA test was performed to compare R(2) values obtained from measured and predicted moisture content (5%-25%, w/w) of SDs. No statistically significant difference was observed between the predictability of NIR and ATR-FTIR methods (p = 0.3504). However, the interactions between the two independent variables, SDs, and analytical methods were statistically significant (p = 0.0002), indicating that the predictability of the analytical method is material dependent. Thus, it would be important to recognize this highly dependent material and analytical method interaction when using NIR moisture analysis in process analytical technology to analyze and control critical quality and performance attributes of raw materials during processing with the goal of ensuring final product quality attributes. © 2014 Wiley Periodicals, Inc. and the American Pharmacists Association J Pharm Sci 103:4012-4020, 2014.
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Epidemiology and management of Buruli ulcer.
Expert Rev Anti Infect Ther
PUBLISHED: 06-12-2014
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Buruli ulcer (Mycobacterium ulcerans infection) is a neglected tropical disease of skin and subcutaneous tissue that can result in long-term cosmetic and functional disability. It is a geographically restricted infection but transmission has been reported in endemic areas in more than 30 countries worldwide. The heaviest burden of disease lies in West and Sub-Saharan Africa where it affects children and adults in subsistence agricultural communities. Mycobacterium ulcerans infection is probably acquired via inoculation of the skin either directly from the environment or indirectly via insect bites. The environmental reservoir and exact route of transmission are not completely understood. It may be that the mode of acquisition varies in different parts of the world. Because of this uncertainty it has been nicknamed the 'mysterious disease'. The therapeutic approach has evolved in the past decade from aggressive surgical resection alone, to a greater focus on antibiotic therapy combined with adjunctive surgery.
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NK cell responses to simian immunodeficiency virus vaginal exposure in naive and vaccinated rhesus macaques.
J. Immunol.
PUBLISHED: 06-04-2014
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NK cell responses to HIV/SIV infection have been well studied in acute and chronic infected patients/monkeys, but little is known about NK cells during viral transmission, particularly in mucosal tissues. In this article, we report a systematic study of NK cell responses to high-dose vaginal exposure to SIVmac251 in the rhesus macaque female reproductive tract (FRT). Small numbers of NK cells were recruited into the FRT mucosa following vaginal inoculation. The influx of mucosal NK cells preceded local virus replication and peaked at 1 wk and, thus, was in an appropriate time frame to control an expanding population of infected cells at the portal of entry. However, NK cells were greatly outnumbered by recruited target cells that fuel local virus expansion and were spatially dissociated from SIV RNA+ cells at the major site of expansion of infected founder populations in the transition zone and adjoining endocervix. The number of NK cells in the FRT mucosa decreased rapidly in the second week, while the number of SIV RNA+ cells in the FRT reached its peak. Mucosal NK cells produced IFN-? and MIP-1?/CCL3 but lacked several markers of activation and cytotoxicity, and this was correlated with inoculum-induced upregulation of the inhibitory ligand HLA-E and downregulation of the activating receptor CD122/IL-2R?. Examination of SIV?nef-vaccinated monkeys suggested that recruitment of NK cells to the genital mucosa was not involved in vaccine-induced protection from vaginal challenge. In summary, our results suggest that NK cells play, at most, a limited role in defenses in the FRT against vaginal challenge.
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A model for lentigo maligna recurrence using melanocyte count as a predictive marker based upon logistic regression analysis of a blinded retrospective review.
J Plast Reconstr Aesthet Surg
PUBLISHED: 05-26-2014
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The pre-malignant skin lesion lentigo maligna (LM) presents a particular challenge. Pathologists demonstrate poor diagnostic concordance and often struggle to assess whether excision margins are truly negative. This can lead to equivocal histology reports and a lack of clear guidance with which surgeons may rationalise their surgical management plans. Based upon the biological principle that tumour burden increases the chance of recurrence, we propose a shift in diagnostic paradigm, using melanocyte count (MC) at an excision margin to predict LM recurrence.
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Dense Si(x)Ge(1-x) (0 < x < 1) materials landscape using extreme conditions and precession electron diffraction.
Inorg Chem
PUBLISHED: 05-14-2014
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High-pressure and -temperature experiments on Ge and Si mixtures to 17 GPa and 1500 K allow us to obtain extended Ge-Si solid solutions with cubic (Ia3) and tetragonal (P4(3)2(1)2) crystal symmetries at ambient pressure. The cubic modification can be obtained with up to 77 atom % Ge and the tetragonal modification for Ge concentrations above that. Together with Hume-Rothery criteria, melting point convergence is employed here as a favored attribute for solid solution formation. These compositionally tunable alloys are of growing interest for advanced transport and optoelectronic applications. Furthermore, the work illustrates the significance of employing precession electron diffraction for mapping new materials landscapes resulting from tailored high-pressure and -temperature syntheses.
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Incretin-modulated beta cell energetics in intact islets of Langerhans.
Mol. Endocrinol.
PUBLISHED: 04-25-2014
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Incretins such as glucagon-like peptide 1 (GLP-1) are released from the gut and potentiate insulin release in a glucose-dependent manner. Although this action is generally believed to hinge on cAMP and protein kinase A signaling, up-regulated beta cell intermediary metabolism may also play a role in incretin-stimulated insulin secretion. By employing recombinant probes to image ATP dynamically in situ within intact mouse and human islets, we sought to clarify the role of GLP-1-modulated energetics in beta cell function. Using these techniques, we show that GLP-1 engages a metabolically coupled subnetwork of beta cells to increase cytosolic ATP levels, an action independent of prevailing energy status. We further demonstrate that the effects of GLP-1 are accompanied by alterations in the mitochondrial inner membrane potential and, at elevated glucose concentration, depend upon GLP-1 receptor-directed calcium influx through voltage-dependent calcium channels. Lastly, and highlighting critical species differences, beta cells within mouse but not human islets respond coordinately to incretin stimulation. Together, these findings suggest that GLP-1 alters beta cell intermediary metabolism to influence ATP dynamics in a species-specific manner, and this may contribute to divergent regulation of the incretin-axis in rodents and man.
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ADCY5 couples glucose to insulin secretion in human islets.
Diabetes
PUBLISHED: 04-16-2014
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Single nucleotide polymorphisms (SNPs) within the ADCY5 gene, encoding adenylate cyclase 5, are associated with elevated fasting glucose and increased type 2 diabetes (T2D) risk. Despite this, the mechanisms underlying the effects of these polymorphic variants at the level of pancreatic ?-cells remain unclear. Here, we show firstly that ADCY5 mRNA expression in islets is lowered by the possession of risk alleles at rs11708067. Next, we demonstrate that ADCY5 is indispensable for coupling glucose, but not GLP-1, to insulin secretion in human islets. Assessed by in situ imaging of recombinant probes, ADCY5 silencing impaired glucose-induced cAMP increases and blocked glucose metabolism toward ATP at concentrations of the sugar >8 mmol/L. However, calcium transient generation and functional connectivity between individual human ?-cells were sharply inhibited at all glucose concentrations tested, implying additional, metabolism-independent roles for ADCY5. In contrast, calcium rises were unaffected in ADCY5-depleted islets exposed to GLP-1. Alterations in ?-cell ADCY5 expression and impaired glucose signaling thus provide a likely route through which ADCY5 gene polymorphisms influence fasting glucose levels and T2D risk, while exerting more minor effects on incretin action.
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Quantitative passive soil vapor sampling for VOCs--Part 4: Flow-through cell.
Environ Sci Process Impacts
PUBLISHED: 04-02-2014
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This paper presents a controlled experiment comparing several quantitative passive samplers for monitoring concentrations of volatile organic compound (VOC) vapors in soil gas using a flow-through cell. This application is simpler than conventional active sampling using adsorptive tubes because the flow rate does not need to be precisely measured and controlled, which is advantageous because the permeability of subsurface materials affects the flow rate and the permeability of geologic materials is highly variable. Using passive samplers in a flow-through cell, the flow rate may not need to be known exactly, as long as it is sufficient to purge the cell in a reasonable time and minimize any negative bias attributable to the starvation effect. An experiment was performed in a 500 mL flow-through cell using a two-factor, one-half fraction fractional factorial test design with flow rates of 80, 670 and 930 mL min(-1) and sample durations of 10, 15 and 20 minutes for each of five different passive samplers (passive Automatic Thermal Desorption Tube, Radiello®, SKC Ultra, Waterloo Membrane Sampler™ and 3M™ OVM 3500). A Summa canister was collected coincident with each passive sampler and analyzed by EPA Method TO-15 to provide a baseline for comparison of the passive sampler concentrations. The passive sampler concentrations were within a factor of 2 of the Summa canister concentrations in 32 of 35 cases. Passive samples collected at the low flow rate and short duration showed low concentrations, which is likely attributable to insufficient purging of the cell after sampler placement.
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Transcriptional profiling of peripheral CD8+T cell responses to SIV?nef and SIVmac251 challenge reveals a link between protective immunity and induction of systemic immunoregulatory mechanisms.
Virology
PUBLISHED: 03-31-2014
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Immunization of macaques with attenuated simian immunodeficiency virus (SIV) with deletions in nef (SIV?nef) is shown to elicit protective immunity to infection by pathogenic SIV, yet the mechanisms that orchestrate protection and prevent pathogenesis remains unknown. We utilized whole-genome transcriptional profiling to reveal molecular signatures of protective immunity in circulating CD8+ T cells of rhesus macaques vaccinated with SIVmac239?nef and challenged with pathogenic SIVmac251. Our findings suggest that protective immunity to pathogenic SIV infection induced by SIVmac239?nef is associated with balanced induction of T cell activation and immunoregulatory mechanisms and dampened activation of interferon-induced signaling pathways and cytolytic enzyme production as compared with pathogenic SIVmac251 infection of unvaccinated controls. We provide evidence that protective immunity to SIVmac251 correlates with induction of biomarkers of T cell activation, differentiation, signaling, and adhesion that were down regulated in unvaccinated controls. The study highlights potential immunomodulatory networks associated with protective immunity against the virus.
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Prognostic factors for morbidity and mortality in elderly patients undergoing acute gastrointestinal surgery: a systematic review.
Can J Surg
PUBLISHED: 03-27-2014
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Elderly patients undergoing acute gastrointestinal (GI) surgery experience increased morbidity and mortality compared with younger and elective patients. Prognostic factors can be used to counsel patients of these risks and, if modifiable, to minimize them. We reviewed the literature on prognostic factors for adverse outcomes in elderly patients undergoing acute GI surgery.
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Home urine C-peptide creatinine ratio can be used to monitor islet transplant function.
Diabetes Care
PUBLISHED: 03-12-2014
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Islet graft function is defined by serum C-peptide in a standardized challenge test. We assessed whether urine C-peptide creatinine ratio (UCPCR) sent from home could provide a viable alternative.
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Pancreas transplantation: solid organ and islet.
Cold Spring Harb Perspect Med
PUBLISHED: 03-10-2014
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Transplantation of the pancreas, either as a solid organ or as isolated islets of Langerhans, is indicated in a small proportion of patients with insulin-dependent diabetes in whom severe complications develop, particularly severe glycemic instability and progressive secondary complications (usually renal failure). The potential to reverse diabetes has to be balanced against the morbidity of long-term immunosuppression. For a patient with renal failure, the treatment of choice is often a simultaneous transplant of the pancreas and kidney (SPK), whereas for a patient with glycemic instability, specifically hypoglycemic unawareness, the choice between a solid organ and an islet transplant has to be individual to the patient. Results of SPK transplantation are comparable to other solid-organ transplants (kidney, liver, heart) and there is evidence of improved quality of life and life expectancy, but the results of solitary pancreas transplantation and islets are inferior with respect to graft survival. There is some evidence of benefit with respect to the progression of secondary diabetic complications in patients with functioning transplants for several years.
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In search for genetic determinants of clinically meaningful differential cardiovascular event reduction by pravastatin in the PHArmacogenetic study of Statins in the Elderly at risk (PHASE)/PROSPER study.
Atherosclerosis
PUBLISHED: 02-12-2014
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Statin therapy is widely used in the prevention and treatment of cardiovascular events and is associated with significant risk reductions. However, there is considerable variation in response to statin therapy both in terms of LDL cholesterol reduction and clinical outcomes. It has been hypothesized that genetic variation contributes importantly to this individual drug response.
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Quantitative passive soil vapor sampling for VOCs--part 3: field experiments.
Environ Sci Process Impacts
PUBLISHED: 02-11-2014
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Volatile organic compounds (VOCs) are commonly associated with contaminated land and may pose a risk to human health via subsurface vapor intrusion to indoor air. Soil vapor sampling is commonly used to assess the nature and extent of VOC contamination, but can be complicated because of the wide range of geologic material permeability and moisture content conditions that might be encountered, the wide variety of available sampling and analysis methods, and several potential causes of bias and variability, including leaks of atmospheric air, adsorption-desorption interactions, inconsistent sampling protocols and varying levels of experience among sampling personnel. Passive sampling onto adsorbent materials has been available as an alternative to conventional whole-gas sample collection for decades, but relationships between the mass sorbed with time and the soil vapor concentration have not been quantitatively established and the relative merits of various commercially available passive samplers for soil vapor concentration measurement is unknown. This paper presents the results of field experiments using several different passive samplers under a wide range of conditions. The results show that properly designed and deployed quantitative passive soil vapor samplers can be used to measure soil vapor concentrations with accuracy and precision comparable to conventional active soil vapor sampling (relative concentrations within a factor of 2 and RSD comparable to active sampling) where the uptake rate is low enough to minimize starvation and the exposure duration is not excessive for weakly retained compounds.
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Quantitative passive soil vapor sampling for VOCs--part 2: laboratory experiments.
Environ Sci Process Impacts
PUBLISHED: 02-11-2014
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Controlled laboratory experiments were conducted to demonstrate the use of passive samplers for soil vapor concentration monitoring. Five different passive samplers were studied (Radiello, SKC Ultra, Waterloo Membrane Sampler, ATD tubes and 3M OVM 3500). Ten different volatile organic compounds were used of varying classes (chlorinated ethanes, ethanes, and methanes, aliphatics and aromatics) and physical properties (vapor pressure, solubility and sorption). Samplers were exposed in randomized triplicates to concentrations of 1, 10 and 100 ppmv, with a relative humidity of ?80%, a temperature of ?24 °C, and a duration of 30 minutes in a chamber with a face velocity of about 5 cm min(-1). Passive samplers are more commonly used for longer sample durations (e.g., 8 hour workday) and higher face velocities (>600 cm min(-1)), so testing to verify the performance for these conditions was needed. Summa canister samples were collected and analyzed by EPA Method TO-15 to establish a baseline for comparison for all the passive samplers. Low-uptake rate varieties of four of the samplers were also tested at 10 ppmv under two conditions; with 5 cm min(-1) face velocity and stagnant conditions to assess whether low or near-zero face velocities would result in a low bias from the starvation effect. The results indicate that passive samplers can provide concentration measurements with accuracy (mostly within a factor of 2) and precision (RSD < 15%) comparable to conventional Summa canister samples and EPA Method TO-15 analysis. Some compounds are challenging for some passive samplers because of uncertainties in the uptake rates, or challenges with retention or recovery.
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Motor activity at age one year does not predict ADHD at seven years.
Int J Methods Psychiatr Res
PUBLISHED: 02-04-2014
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We have examined the predictive utility of motor activity in infancy towards diagnosis of attention deficit hyperactivity disorder (ADHD) in later childhood. We conducted a nested case-control study using videos of infants in the Avon Longitudinal Study of Parents and Children (ALSPAC). Sixty videos of children who received any Development and Well-being Assessment (DAWBA) psychiatric diagnosis at age 91 months (including 16 with ADHD) plus two controls per case were selected for data analysis. Body movements were measured at age one year: associations between motor activity-derived variables using factor analysis, and later ADHD diagnoses were sought. No significant association was found between infant motor activity and later ADHD. A positive association between motor activity and inattentive ADHD was found in males. Motor activity at age one year did not predict ADHD at age seven years. The positive association with inattentive ADHD in males requires further investigation.
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Treatment and prevention of Mycobacterium ulcerans infection (Buruli ulcer) in Australia: guideline update.
Med. J. Aust.
PUBLISHED: 01-29-2014
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• Guidelines reflecting contemporary clinical practice in the management of Buruli ulcer (Mycobacterium ulcerans infection) in Australia were published in 2007. • Management has continued to evolve, as new evidence has become available from randomised trials, case series and increasing clinical experience with oral antibiotic therapy. • Therefore, guidelines on the diagnosis, treatment and prevention of Buruli ulcer in Australia have been updated. They include guidance on the new role of antibiotics as first-line therapy; the shortened duration of antibiotic treatment and the use of all-oral antibiotic regimens; the continued importance, timing and role of surgery; the recognition and management of paradoxical reactions during antibiotic treatment; and updates on the prevention of disease.
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Application of multivariate methods to evaluate the functionality of bovine- and vegetable-derived magnesium stearate.
J Pharm Sci
PUBLISHED: 01-15-2014
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This work distinguishes and quantifies the effects of bovine- and vegetable-derived magnesium stearate (MgSt) molecular and macroscopic properties on lubrication efficiency using multivariate analysis. Principal component analysis (PCA) and partial least-square regression (PLS) were used to evaluate and quantify the lubricant effectiveness on a model tablet formulation. PCA score and loading plots showed a separation of model formulations based on the MgSt sources, which indicated different bovine- and vegetable-derived MgSt lubrication potential. PLS quantified the MgSt molecular [enthalpy of dehydration (?Hd), enthalpy of melting (?Hm), percent crystallinity, and moisture content] and macroscopic [particle size (d50 ), specific surface area (SSA-MgSt), and MgSt Hausner ratio (HF-MgSt)] properties, their interactions, and square effects on formulation powder flow and tableting properties relating to MgSt's lubrication effectiveness. For crystalline MgSt, moisture content, HF-MgSt, d50 , and SSA-MgSt showed a major influence on the lubrication efficiency compared with the other MgSt molecular properties (percent crystallinity, ?Hm, and ?Hd). Amorphous MgSt showed poor lubrication, and none of its molecular or macroscopic properties showed significant effects on lubrication efficiency.
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Contribution of household herbicide usage to glyphosate and its degradate aminomethylphosphonic acid in surface water drains.
Pest Manag. Sci.
PUBLISHED: 01-03-2014
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It is necessary to understand the extent to which different sources of pesticides contribute to surface water contamination in order to focus preventive measures appropriately. The extent to which glyphosate use in the home and garden sector may contribute to surface water contamination has not previously been quantified. The aim of this study was to quantify the widely used herbicide glyphosate and its degradation product aminomethylphosphonic acid (AMPA) in surface water drains (storm drains) that could be attributed to amateur, non-professional usage alone.
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Molecular epidemiology of enterococcal bacteremia in Australia.
J. Clin. Microbiol.
PUBLISHED: 01-03-2014
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Enterococci are a major cause of health care-associated infections and account for approximately 10% of all bacteremias globally. The aim of this study was to determine the proportion of enterococcal bacteremia isolates in Australia that are antimicrobial resistant, with particular emphasis on susceptibility to ampicillin and the glycopeptides, and to characterize the molecular epidemiology of the Enterococcus faecalis and Enterococcus faecium isolates. From 1 January to 31 December 2011, 1,079 unique episodes of bacteremia were investigated, of which 95.8% were caused by either E. faecalis (61.0%) or E. faecium (34.8%). The majority of bacteremias were health care associated, and approximately one-third were polymicrobial. Ampicillin resistance was detected in 90.4% of E. faecium isolates but was not detected in E. faecalis isolates. Vancomycin nonsusceptibility was reported in 0.6% and 36.5% of E. faecalis and E. faecium isolates, respectively. Unlike Europe and the United States, where vancomycin resistance in E. faecium is predominately due to the acquisition of the vanA operon, 98.4% of E. faecium isolates harboring van genes carried the vanB operon, and 16.1% of the vanB E. faecium isolates had vancomycin MICs at or below the susceptible breakpoint of the CLSI. Although molecular typing identified 126 E. faecalis pulsed-field gel electrophoresis pulsotypes, >50% belonged to two pulsotypes that were isolated across Australia. E. faecium consisted of 73 pulsotypes from which 43 multilocus sequence types were identified. Almost 90% of the E. faecium isolates were identified as CC17 clones, of which approximately half were characterized as ST203, which was isolated Australia-wide. In conclusion, the Australian Enterococcal Sepsis Outcome Programme (AESOP) study has shown that although they are polyclonal, enterococcal bacteremias in Australia are frequently caused by ampicillin-resistant vanB E. faecium.
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Potential wildlife sentinels for monitoring the endemic spread of human buruli ulcer in South-East australia.
PLoS Negl Trop Dis
PUBLISHED: 01-01-2014
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The last 20 years has seen a significant series of outbreaks of Buruli/Bairnsdale Ulcer (BU), caused by Mycobacterium ulcerans, in temperate south-eastern Australia (state of Victoria). Here, the prevailing view of M. ulcerans as an aquatic pathogen has been questioned by recent research identifying native wildlife as potential terrestrial reservoirs of infection; specifically, tree-dwelling common ringtail and brushtail possums. In that previous work, sampling of environmental possum faeces detected a high prevalence of M. ulcerans DNA in established endemic areas for human BU on the Bellarine Peninsula, compared with non-endemic areas. Here, we report research from an emergent BU focus recently identified on the Mornington Peninsula, confirming associations between human BU and the presence of the aetiological agent in possum faeces, detected by real-time PCR targeting M. ulcerans IS2404, IS2606 and KR. Mycobacterium ulcerans DNA was detected in 20/216 (9.3%) ground collected ringtail possum faecal samples and 4/6 (66.6%) brushtail possum faecal samples. The distribution of the PCR positive possum faecal samples and human BU cases was highly focal: there was a significant non-random cluster of 16 M. ulcerans positive possum faecal sample points detected by spatial scan statistics (P<0.0001) within a circle of radius 0.42 km, within which were located the addresses of 6/12 human cases reported from the area to date; moreover, the highest sample PCR signal strength (equivalent to ?10(6) organisms per gram of faeces) was found in a sample point located within this cluster radius. Corresponding faecal samples collected from closely adjacent BU-free areas were predominantly negative. Possums may be useful sentinels to predict endemic spread of human BU in Victoria, for public health planning. Further research is needed to establish whether spatial associations represent evidence of direct or indirect transmission between possums and humans, and the mechanism by which this may occur.
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Clinical, microbiological and pathological findings of Mycobacterium ulcerans infection in three Australian Possum species.
PLoS Negl Trop Dis
PUBLISHED: 01-01-2014
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Buruli ulcer (BU) is a skin disease caused by Mycobacterium ulcerans, with endemicity predominantly in sub-Saharan Africa and south-eastern Australia. The mode of transmission and the environmental reservoir(s) of the bacterium and remain elusive. Real-time PCR investigations have detected M. ulcerans DNA in a variety of Australian environmental samples, including the faeces of native possums with and without clinical evidence of infection. This report seeks to expand on previously published findings by the authors' investigative group with regards to clinical and subclinical disease in selected wild possum species in BU-endemic areas of Victoria, Australia.
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Combining organophosphate treated wall linings and long-lasting insecticidal nets for improved control of pyrethroid resistant Anopheles gambiae.
PLoS ONE
PUBLISHED: 01-01-2014
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New approaches to delivering insecticides need to be developed to improve malaria vector control. Insecticidal durable wall lining (DL) and net wall hangings (NWH) are novel alternatives to indoor residual spraying which can be produced in a long-lasting format. Non-pyrethroid versions could be used in combination with long-lasting insecticidal nets for improved control and management of insecticide resistant vector populations.
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Using simulation technology to teach diabetes care management skills to resident physicians.
J Diabetes Sci Technol
PUBLISHED: 10-16-2013
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Simulation is widely used to teach medical procedures. Our goal was to develop and implement an innovative virtual model to teach resident physicians the cognitive skills of type 1 and type 2 diabetes management.
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Epidemiology of bloodstream infections caused by Acinetobacter baumannii and impact of drug resistance to both carbapenems and ampicillin-sulbactam on clinical outcomes.
Antimicrob. Agents Chemother.
PUBLISHED: 10-07-2013
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Acinetobacter baumannii has become a leading cause of bloodstream infections (BSI) in health care settings. Although the incidence of infection with carbapenem- and ampicillin-sulbactam-resistant (CASR) A. baumannii has increased, there is a scarcity of studies which investigate BSI caused by CASR A. baumannii. A retrospective cohort study was conducted on adult patients with BSI caused by A. baumannii and who were admitted to the Detroit Medical Center between January 2006 and April 2009. Medical records were queried for patients demographics, antimicrobial exposures, comorbidities, hospital stay, and clinical outcomes. Bivariate analyses and logistic regression were employed in the study. Two hundred seventy-four patients with BSI caused by A. baumannii were included in the study: 68 (25%) caused by CASR A. baumannii and 206 (75%) caused by non-CASR A. baumannii. In multivariate analysis, factors associated with BSI caused by CASR A. baumannii included admission with a rapidly fatal condition (odds ratio [OR] = 2.83, 95% confidence interval [CI] = 1.27 to 6.32, P value = 0.01) and prior use of antimicrobials (OR = 2.83, 95% CI = 1.18 to 6.78, P value = 0.02). In-hospital mortality rates for BSI caused by CASR A. baumannii were significantly higher than those for non-CASR A. baumannii-induced BSI (43% versus 20%; OR = 3.0, 95% CI = 1.60 to 5.23, P value < 0.001). However, after adjusting for potential confounders, the association between BSI caused by CASR A. baumannii and increased risk of in-hospital mortality was not significant (OR = 1.15, 95% CI = 0.51 to 2.63, P value = 0.74). This study demonstrated that CASR A. baumannii had a distinct epidemiology compared to more susceptible A. baumannii strains; however, clinical outcomes were similar for the two groups. Admission with a rapidly fatal condition was an independent predictor for both CASR A. baumannii and in-hospital mortality.
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The incubation period of Buruli ulcer (Mycobacterium ulcerans infection).
PLoS Negl Trop Dis
PUBLISHED: 10-01-2013
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Buruli Ulcer (BU) is caused by the environmental microbe Mycobacterium ulcerans. Despite unclear transmission, contact with a BU endemic region is the key known risk factor. In Victoria, Australia, where endemic areas have been carefully mapped, we aimed to estimate the Incubation Period (IP) of BU by interviewing patients who reported defined periods of contact with an endemic area prior to BU diagnosis.
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Improving the efficiency of stroke trials: feasibility and efficacy of group adjudication of functional end points.
Stroke
PUBLISHED: 09-19-2013
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Use of the modified Rankin scale (mRS) in multicenter trials may be limited by interobserver variability. We assessed the effect of this on trial power and developed a novel group adjudication approach.
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Genomic insights to control the emergence of vancomycin-resistant enterococci.
MBio
PUBLISHED: 08-15-2013
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Nosocomial outbreaks of vancomycin-resistant Enterococcus faecium (VREfm) are thought to occur by transmission of VREfm between patients, predicting that infection control interventions will limit cross-transmission. Despite implementation of such strategies, the incidence of VREfm infections continues to rise. We aimed to use genomics to better understand the epidemiology of E. faecium within a large hospital and investigate the reasons for failure of infection control strategies. Whole-genome sequencing was performed on 61 E. faecium (36 VREfm) isolates, predominately from blood cultures collected at a single hospital between 1998 and 2009, and on five vanB-positive anaerobic commensal bacteria isolated from human feces. Phylogenomic analysis and precise mapping of the vanB gene, which contains the Tn1549 transposon, showed that at least 18 of the 36 VREfm isolates had acquired the transposon via independent insertion events, indicating de novo generation of VREfm rather than cross-transmission. Furthermore, Tn1549 sequences found in 15 of the 36 VREfm isolates were the same as the Tn1549 sequence from one of the gut anaerobes. National and international comparator E. faecium isolates were phylogenetically interspersed with isolates from our hospital, suggesting that our findings might be globally representative. These data demonstrate that VREfm generation within a patient is common, presumably occurring in the human bowel during antibiotic therapy, and help explain our inability to reduce VREfm infections. A recommendation from our findings is that infection control practices should include screening patients for specific hospital clones of vancomycin-susceptible E. faecium rather than just VREfm.
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Long-term carriage of vancomycin-resistant enterococci in patients discharged from hospitals: a 12-year retrospective cohort study.
J. Clin. Microbiol.
PUBLISHED: 08-07-2013
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Contact precautions are recommended in hospitals to prevent the transmission of vancomycin-resistant enterococci (VRE); however, there is no clear policy for how long patients should be under contact precautions due to a lack of information on the duration of carriage of these organisms. We conducted a retrospective cohort study to understand the duration of carriage of VRE (by screening of a single stool culture) and associated factors among patients who had been identified with VRE infection and/or colonization since the year 2000 at our health facilities. Of the 345 eligible participants, 136 did not respond, 90 declined to participate, and 16 did not send in the required specimens. Of the 103 remaining participants, 13 were found to have current VRE fecal carriage. The proportion of colonized patients fell from 40% (2/5) in the first year to 23.3% (7/30) in year 4. None of the 40 patients who had VRE detected >4 years prior were found to be colonized at the time of the study. The longest duration of detected VRE positivity was 46.5 months. Univariate analysis revealed that recent exposure to any antibiotics (P = 0.016), multiple antibiotics (P = 0.001), amoxicillin-clavulanic acid (P = 0.021), piperacillin-tazobactam (P = 0.007), glycopeptides (P < 0.001), meropenem (P = 0.007), aminoglycosides (P = 0.021), or fluoroquinolones (P = 0.021), being the index case in a clinical specimen (P = 0.016), and recent hospitalization (P < 0.001) were significantly associated with continued carriage on follow-up. In the surviving outpatients, a significant proportion appeared to clear VRE carriage. Our results suggest that in the absence of recent risk factors, such as hospitalization or antibiotic use, patients with a remote history of colonization (>4 years) may no longer require contact isolation precautions.
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Ex vivo expanded human regulatory T cells can prolong survival of a human islet allograft in a humanized mouse model.
Transplantation
PUBLISHED: 08-07-2013
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Human regulatory T cells (Treg) offer an attractive adjunctive therapy to reduce current reliance on lifelong, nonspecific immunosuppression after transplantation. Here, we evaluated the ability of ex vivo expanded human Treg to prevent the rejection of islets of Langerhans in a humanized mouse model and examined the mechanisms involved.
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Lipotoxicity disrupts incretin-regulated human ? cell connectivity.
J. Clin. Invest.
PUBLISHED: 07-11-2013
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Pancreatic ? cell dysfunction is pathognomonic of type 2 diabetes mellitus (T2DM) and is driven by environmental and genetic factors. ? cell responses to glucose and to incretins such as glucagon-like peptide-1 (GLP-1) and glucose-dependent insulinotropic polypeptide (GIP) are altered in the disease state. While rodent ? cells act as a coordinated syncytium to drive insulin release, this property is unexplored in human islets. In situ imaging approaches were therefore used to monitor in real time the islet dynamics underlying hormone release. We found that GLP-1 and GIP recruit a highly coordinated subnetwork of ? cells that are targeted by lipotoxicity to suppress insulin secretion. Donor BMI was negatively correlated with subpopulation responses to GLP-1, suggesting that this action of incretin contributes to functional ? cell mass in vivo. Conversely, exposure of mice to a high-fat diet unveiled a role for incretin in maintaining coordinated islet activity, supporting the existence of species-specific strategies to maintain normoglycemia. These findings demonstrate that ? cell connectedness is an inherent property of human islets that is likely to influence incretin-potentiated insulin secretion and may be perturbed by diabetogenic insults to disrupt glucose homeostasis in humans.
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Argonaute2 Mediates Compensatory Expansion of the Pancreatic ? Cell.
Cell Metab.
PUBLISHED: 05-04-2013
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Pancreatic ? cells adapt to compensate for increased metabolic demand during insulin resistance. Although the microRNA pathway has an essential role in ? cell proliferation, the extent of its contribution is unclear. Here, we report that miR-184 is silenced in the pancreatic islets of insulin-resistant mouse models and type 2 diabetic human subjects. Reduction of miR-184 promotes the expression of its target Argonaute2 (Ago2), a component of the microRNA-induced silencing complex. Moreover, restoration of miR-184 in leptin-deficient ob/ob mice decreased Ago2 and prevented compensatory ? cell expansion. Loss of Ago2 during insulin resistance blocked ? cell growth and relieved the regulation of miR-375-targeted genes, including the growth suppressor Cadm1. Lastly, administration of a ketogenic diet to ob/ob mice rescued insulin sensitivity and miR-184 expression and restored Ago2 and ? cell mass. This study identifies the targeting of Ago2 by miR-184 as an essential component of the compensatory response to regulate proliferation according to insulin sensitivity.
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Genomic analysis of teicoplanin resistance emerging during treatment of vanB vancomycin-resistant Enterococcus faecium infections in solid organ transplant recipients including donor-derived cases.
J. Antimicrob. Chemother.
PUBLISHED: 04-23-2013
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We noted four cases of apparent in vivo emergence of teicoplanin resistance during failed therapy for initially teicoplanin-susceptible vanB vancomycin-resistant Enterococcus faecium (VREfm) infections in solid organ transplant recipients at our institution over a 12 month period. We investigated if in vivo emergence of resistance had occurred, if transplant-related vancomycin-resistant Enterococcus (VRE) infections had occurred and identified clinical predictors of resistance emergence.
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Comparative analysis of the complete genome of an epidemic hospital sequence type 203 clone of vancomycin-resistant Enterococcus faecium.
BMC Genomics
PUBLISHED: 03-19-2013
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In this report we have explored the genomic and microbiological basis for a sustained increase in bloodstream infections at a major Australian hospital caused by Enterococcus faecium multi-locus sequence type (ST) 203, an outbreak strain that has largely replaced a predecessor ST17 sequence type.
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Multi-functional plasmacytoid dendritic cells redistribute to gut tissues during simian immunodeficiency virus infection.
Immunology
PUBLISHED: 03-17-2013
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The objective of this study was to determine the systemic effects of chronic simian immunodeficiency virus (SIV) infection on plasmacytoid dendritic cells (pDCs). pDCs play a critical role in antiviral immunity, but current data are conflicting on whether pDCs inhibit HIV/SIV replication, or, alternatively, contribute to chronic immune activation and disease. Furthermore, previous pDC studies have been complicated by incomplete descriptions of generalized depletion during HIV/SIV infection, and the effects of infection on pDCs outside peripheral blood remain unclear. In scheduled-sacrifice studies of naive and chronically SIV-infected rhesus macaques we evaluated the distribution and functionality of pDCs in multiple tissues using surface and intracellular polychromatic flow cytometry. As previously observed, pDCs were reduced in peripheral blood and spleens, but were also depleted in non-lymphoid organs such as the liver. Interestingly, pDCs accumulated up to fourfold in jejunum, colon and gut-draining lymph nodes, but not in peripheral lymph nodes. Most unexpectedly, SIV infection induced a multi-functional interferon-?, tumour necrosis factor-?, and macrophage inflammatory protein-1? cytokine secretion phenotype, whereas in normal animals these were generally distinct and separate functions. Herein we show a systemic redistribution of pDCs to gut tissues and gut-draining lymph nodes during chronic SIV infection, coupled to a novel multi-functional cytokine-producing phenotype. While pDC accumulation in the mucosa could aid in virus control, over-production of cytokines from these cells could also contribute to the increased immune activation in the gut mucosa commonly associated with progressive lentivirus infections.
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Prediction of 7-year psychopathology from mother-infant joint attention behaviours: a nested case-control study.
BMC Pediatr
PUBLISHED: 03-15-2013
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To investigate whether later diagnosis of psychiatric disorder can be predicted from analysis of mother-infant joint attention (JA) behaviours in social-communicative interaction at 12 months.
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The microbiological and clinical outcome of guide wire exchanged versus newly inserted antimicrobial surface treated central venous catheters.
Crit Care
PUBLISHED: 03-15-2013
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The management of suspected central venous catheter (CVC)-related sepsis by guide wire exchange (GWX) is not recommended. However, GWX for new antimicrobial surface treated (AST) triple lumen CVCs has never been studied. We aimed to compare the microbiological outcome of triple lumen AST CVCs inserted by GWX (GWX-CVCs) with newly inserted triple lumen AST CVCs (NI-CVCs).
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Peripheral intravenous catheter-associated Staphylococcus aureus bacteraemia: more than 5 years of prospective data from two tertiary health services.
Med. J. Aust.
PUBLISHED: 03-13-2013
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To determine the incidence, risk factors for and outcomes of Staphylococcus aureus bacteraemia (SAB) associated with peripheral intravenous catheters (PIVCs).
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Discovery of 4-amino-N-[(1S)-1-(4-chlorophenyl)-3-hydroxypropyl]-1-(7H-pyrrolo[2,3-d]pyrimidin-4-yl)piperidine-4-carboxamide (AZD5363), an orally bioavailable, potent inhibitor of Akt kinases.
J. Med. Chem.
PUBLISHED: 02-26-2013
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Wide-ranging exploration of analogues of an ATP-competitive pyrrolopyrimidine inhibitor of Akt led to the discovery of clinical candidate AZD5363, which showed increased potency, reduced hERG affinity, and higher selectivity against the closely related AGC kinase ROCK. This compound demonstrated good preclinical drug metabolism and pharmacokinetics (DMPK) properties and, after oral dosing, showed pharmacodynamic knockdown of phosphorylation of Akt and downstream biomarkers in vivo, and inhibition of tumor growth in a breast cancer xenograft model.
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Can we quantify harm in general practice records? An assessment of precision and power using computer simulation.
BMC Med Res Methodol
PUBLISHED: 02-25-2013
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Estimating harm rates for specific patient populations and detecting significant changes in them over time are essential if patient safety in general practice is to be improved. Clinical record review (CRR) is arguably the most suitable method for these purposes, but the optimal values and combinations of its parameters (such as numbers of records and practices) remain unknown. Our aims were to: 1. Determine and quantify CRR parameters; 2. Assess the precision and power of feasible CRR scenarios; and 3. Quantify the minimum requirements for adequate precision and acceptable power.
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No monkey business: why studying NK cells in non-human primates pays off.
Front Immunol
PUBLISHED: 01-27-2013
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Human NK (hNK) cells play a key role in mediating host immune responses against various infectious diseases. For practical reasons, the majority of the data on hNK cells has been generated using peripheral blood lymphocytes. In contrast, our knowledge of NK cells in human tissues is limited, and not much is known about developmental pathways of hNK cell subpopulations in vivo. Although research in mice has elucidated a number of fundamental features of NK cell biology, mouse, and hNK cells significantly differ in their subpopulations, functions, and receptor repertoires. Thus, there is a need for a model that is more closely related to humans and yet allows experimental manipulations. Non-human primate models offer numerous opportunities for the study of NK cells, including the study of the role of NK cells after solid organ and stem cell transplantation, as well as in acute viral infection. Macaque NK cells can be depleted in vivo or adoptively transferred in an autologous system. All of these studies are either difficult or unethical to carry out in humans. Here we highlight recent advances in rhesus NK cell research and their parallels in humans. Using high-throughput transcriptional profiling, we demonstrate that the human CD56(bright) and CD56(dim) NK cell subsets have phenotypically and functionally analogous counterparts in rhesus macaques. Thus, the use of non-human primate models offers the potential to substantially advance hNK cell research.
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The miRNA profile of human pancreatic islets and beta-cells and relationship to type 2 diabetes pathogenesis.
PLoS ONE
PUBLISHED: 01-25-2013
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Recent advances in the understanding of the genetics of type 2 diabetes (T2D) susceptibility have focused attention on the regulation of transcriptional activity within the pancreatic beta-cell. MicroRNAs (miRNAs) represent an important component of regulatory control, and have proven roles in the development of human disease and control of glucose homeostasis. We set out to establish the miRNA profile of human pancreatic islets and of enriched beta-cell populations, and to explore their potential involvement in T2D susceptibility. We used Illumina small RNA sequencing to profile the miRNA fraction in three preparations each of primary human islets and of enriched beta-cells generated by fluorescence-activated cell sorting. In total, 366 miRNAs were found to be expressed (i.e. >100 cumulative reads) in islets and 346 in beta-cells; of the total of 384 unique miRNAs, 328 were shared. A comparison of the islet-cell miRNA profile with those of 15 other human tissues identified 40 miRNAs predominantly expressed (i.e. >50% of all reads seen across the tissues) in islets. Several highly-expressed islet miRNAs, such as miR-375, have established roles in the regulation of islet function, but others (e.g. miR-27b-3p, miR-192-5p) have not previously been described in the context of islet biology. As a first step towards exploring the role of islet-expressed miRNAs and their predicted mRNA targets in T2D pathogenesis, we looked at published T2D association signals across these sites. We found evidence that predicted mRNA targets of islet-expressed miRNAs were globally enriched for signals of T2D association (p-values <0.01, q-values <0.1). At six loci with genome-wide evidence for T2D association (AP3S2, KCNK16, NOTCH2, SCL30A8, VPS26A, and WFS1) predicted mRNA target sites for islet-expressed miRNAs overlapped potentially causal variants. In conclusion, we have described the miRNA profile of human islets and beta-cells and provide evidence linking islet miRNAs to T2D pathogenesis.
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Vancomycin AUC/MIC ratio and 30-day mortality in patients with Staphylococcus aureus bacteremia.
Antimicrob. Agents Chemother.
PUBLISHED: 01-18-2013
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A ratio of the vancomycin area under the concentration-time curve to the MIC (AUC/MIC) of ? 400 has been associated with clinical success when treating Staphylococcus aureus pneumonia, and this target was recommended by recently published vancomycin therapeutic monitoring consensus guidelines for treating all serious S. aureus infections. Here, vancomycin serum trough levels and vancomycin AUC/MIC were evaluated in a "real-world" context by following a cohort of 182 patients with S. aureus bacteremia (SAB) and analyzing these parameters within the critical first 96 h of vancomycin therapy. The median vancomycin trough level at this time point was 19.5 mg/liter. There was a significant difference in vancomycin AUC/MIC when using broth microdilution (BMD) compared with Etest MIC (medians of 436.1 and 271.5, respectively; P < 0.001). Obtaining the recommended vancomycin target AUC/MIC of ? 400 using BMD was not associated with lower 30-day all-cause or attributable mortality from SAB (P = 0.132 and P = 0.273, respectively). However, an alternative vancomycin AUC/MIC of >373, derived using classification and regression tree analysis, was associated with reduced mortality (P = 0.043) and remained significant in a multivariable model. This study demonstrated that we obtained vancomycin trough levels in the target therapeutic range early during the course of therapy and that obtaining a higher vancomycin AUC/MIC (in this case, >373) within 96 h was associated with reduced mortality. The MIC test method has a significant impact on vancomycin AUC/MIC estimation. Clinicians should be aware that the current target AUC/MIC of ? 400 was derived using the reference BMD method, so adjustments to this target need to be made when calculating AUC/MIC ratio using other MIC testing methods.
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The fish tank strikes again: Metachronous nontuberculous mycobacterial skin infection in an immunosuppressed host.
Australas. J. Dermatol.
PUBLISHED: 01-16-2013
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An 82-year-old woman on long-term prednisolone for chronic obstructive airways disease presented with a 2-month history of nodules on her left forearm. This occurred 10 years after nodules on her right forearm caused by a culture-proven Mycobacterium marinum infection. Histopathological examination, polymerase chain reaction and culture of biopsy specimens were positive for M. chelonae. To our knowledge this is the first case of metachronous nontuberculous mycobacterial skin infection reported, and it highlights the diagnostic and therapeutic challenges of such infections.
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Location and Dynamics of the Immunodominant CD8 T Cell Response to SIV?nef Immunization and SIVmac251 Vaginal Challenge.
PLoS ONE
PUBLISHED: 01-01-2013
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Live-attenuated SIV vaccines (LAVs) have been the most effective to date in preventing or partially controlling infection by wild-type SIV in non-human primate models of HIV-1 transmission to women acting by mechanisms of protection that are not well understood. To gain insights into mechanisms of protection by LAVs that could aid development of effective vaccines to prevent HIV-1 transmission to women, we used in situ tetramer staining to determine whether increased densities or changes in the local distribution of SIV-specific CD8 T cells correlated with the maturation of SIV?nef vaccine-induced protection prior to and after intra-vaginal challenge with wild-type SIVmac251. We evaluated the immunodominant Mamu-A1*001:01/Gag (CM9) and Mamu-A1*001:01/Tat (SL8) epitope response in genital and lymphoid tissues, and found that tetramer+ cells were present at all time points examined. In the cervical vaginal tissues, most tetramer+ cells were distributed diffusely throughout the lamina propria or co-localized with other CD8 T cells within lymphoid aggregates. The distribution and densities of the tetramer+ cells at the portal of entry did not correlate with the maturation of protection or change after challenge. Given these findings, we discuss the possibility that changes in other aspects of the immune system, including the quality of the resident population of virus-specific effector CD8 T cells could contribute to maturation of protection, as well as the potential for vaccine strategies that further increase the size and quality of this effector population to prevent HIV-1 transmission.
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MDHS 25 revisited: part 2, modified sampling and analytical procedures applied to HDI-based isocyanates.
Ann Occup Hyg
PUBLISHED: 12-26-2011
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The method that is probably the most commonly used worldwide for the determination of total organic isocyanates (NCO) in air is the Health and Safety Executive method, MDHS 25/3, Organic Isocyanates in Air, and its variants. This paper summarizes some of the research and development work carried out by Health and Safety Laboratory on this method since its publication in 1999 with the eventual aim of incorporating this work in an updated version of MDHS 25 (i.e. MDHS 25/4). The work falls into two main areas: use of liquid chromatography/mass spectrometry (LC/MS) as an alternative to liquid chromatography with electrochemical and ultraviolet/visible detection (LC/EC/UV) and evaluation of solid-phase sampling techniques as an alternative to the impinger-filter combination stated in MDHS 25/3. This paper deals primarily with HDI-based NCO but some comments regarding aromatic NCO (MDI and TDI) are included for completeness. An LC/MS/MS version of MDHS 25/3 has been developed that gives improved performance to the classical version of MDHS 25/3 using EC/UV detection. The LC/MS/MS offers significant advantages over the EC/UV version of MDHS 25/3 in that it is more sensitive, provides improved identification, and has been found to be easier to use. The solid-phase samplers evaluated were a double-thickness glass-fibre (GF/B) filter coated with 1-(2-methoxyphenyl)piperazine (MP) reagent in an IOM (Institute of Occupational Medicine) sampling head (FIN-MP sampler) and an MP-impregnated polyurethane foam sponge (PUF) with an MP-coated glass-fibre (GF/A) backup filter also in an IOM sampling head (Rudzinski sampler). Both samplers were found to give acceptable performance for the sampling of oligomeric HDI in workplace air and in laboratory simulations when compared to the impinger-filter combination at levels corresponding to the UK short-term limit (70 ?g m(-3)). For practical reasons, the FIN-MP sampler was the preferred alternative.
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Outcomes from the first 2 years of the Australian National Hand Hygiene Initiative.
Med. J. Aust.
PUBLISHED: 11-24-2011
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To report outcomes from the first 2 years of the National Hand Hygiene Initiative (NHHI), a hand hygiene (HH) culture-change program implemented in all Australian hospitals to improve health care workers HH compliance, increase use of alcohol-based hand rub and reduce the risk of health care-associated infections.
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Impact of swine influenza and quarantine measures on patients and households during the H1N1/09 pandemic.
Scand. J. Infect. Dis.
PUBLISHED: 11-22-2011
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To assess the secondary attack rates (SAR) and impact of the 2009 H1N1 epidemic in Melbourne, Victoria, Australia, and the measures implemented to control household transmission.
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Gastroschisis: one year outcomes from national cohort study.
BMJ
PUBLISHED: 11-18-2011
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To describe one year outcomes for a national cohort of infants with gastroschisis.
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High-accuracy acoustic detection of nonclassical component of material nonlinearity.
J. Acoust. Soc. Am.
PUBLISHED: 11-18-2011
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The aim is to assess the nonclassical component of material nonlinearity in several classes of materials with weak, intermediate, and high nonlinear properties. In this contribution, an optimized nonlinear resonant ultrasound spectroscopy (NRUS) measuring and data processing protocol applied to small samples is described. The protocol is used to overcome the effects of environmental condition changes that take place during an experiment, and that may mask the intrinsic nonlinearity. External temperature fluctuation is identified as a primary source of measurement contamination. For instance, a variation of 0.1?°C produced a frequency variation of 0.01%, which is similar to the expected nonlinear frequency shift for weakly nonlinear materials. In order to overcome environmental effects, the reference frequency measurements are repeated before each excitation level and then used to compute nonlinear parameters. Using this approach, relative resonant frequency shifts of 10(-5) can be measured, which is below the limit of 10(-4) often considered as the limit of NRUS sensitivity under common experimental conditions. Due to enhanced sensitivity resulting from the correction procedure applied in this work, nonclassical nonlinearity in materials that before have been assumed to only be classically nonlinear in past work (steel, brass, and aluminum) is reported.
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Time reversal reconstruction of finite sized sources in elastic media.
J. Acoust. Soc. Am.
PUBLISHED: 10-07-2011
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The ability of the time reversal process to reconstruct sources of finite size relative to a wavelength is investigated. Specifically the quality of the spatial reconstruction of a finite sized source will be presented through the use of time reversal experiments conducted on an aluminum plate. The data presented in the paper show that time reversal can reconstruct a source equally well regarding less of its size, when the source is a half wavelength or less in size. The quality of spatial reconstruction when the source is larger than a half wavelength progressively decreases with the size of the source.
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Vaccine protection against simian immunodeficiency virus in monkeys using recombinant gamma-2 herpesvirus.
J. Virol.
PUBLISHED: 09-07-2011
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Recombinant strains of replication-competent rhesus monkey rhadinovirus (RRV) were constructed in which strong promoter/enhancer elements were used to drive expression of simian immunodeficiency virus (SIV) Env or Gag or a Rev-Tat-Nef fusion protein. Cultured rhesus monkey fibroblasts infected with each recombinant strain were shown to express the expected protein. Three RRV-negative and two RRV-positive rhesus monkeys were inoculated intravenously with a mixture of these three recombinant RRVs. Expression of SIV Gag was readily detected in lymph node biopsy specimens taken at 3 weeks postimmunization. Impressive anti-SIV cellular immune responses were elicited on the basis of major histocompatibility complex (MHC) tetramer staining and gamma interferon enzyme-linked immunospot (ELISPOT) assays. Responses were much greater in magnitude in the monkeys that were initially RRV negative but were still readily detected in the two monkeys that were naturally infected with RRV at the time of immunization. By 3 weeks postimmunization, responses measured by MHC tetramer staining in the two Mamu-A*01(+) RRV-negative monkeys reached 9.3% and 13.1% of all CD8(+) T cells in peripheral blood to the Gag CM9 epitope and 2.3% and 7.3% of all CD8(+) T cells in peripheral blood to the Tat SL8 epitope. Virus-specific CD8(+) T cell responses persisted at high levels up to the time of challenge at 18 weeks postimmunization, and responding cells maintained an effector memory phenotype. Despite the ability of the RRVenv recombinant to express high levels of Env in cultured cells, and despite the appearance of strong anti-RRV antibody responses in immunized monkeys, anti-Env antibody responses were below our ability to detect them. Immunized monkeys, together with three unimmunized controls, were challenged intravenously with 10 monkey infectious doses of SIVmac239. All five immunized monkeys and all three controls became infected with SIV, but peak viral loads were 1.2 to 3.0 log(10) units lower and chronic-phase viral loads were 1.0 to 3.0 log(10) units lower in immunized animals than the geometric mean of unimmunized controls. These differences were statistically significant. Anti-Env antibody responses following challenge indicated an anamnestic response in the vaccinated monkeys. These findings further demonstrate the potential of recombinant herpesviruses as preventive vaccines for AIDS. We hypothesize that this live, replication-competent, persistent herpesvirus vector could match, or come close to matching, live attenuated strains of SIV in the degree of protection if the difficulty with elicitation of anti-Env antibody responses can be overcome.
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Genome-wide association identifies nine common variants associated with fasting proinsulin levels and provides new insights into the pathophysiology of type 2 diabetes.
Rona J Strawbridge, Josée Dupuis, Inga Prokopenko, Adam Barker, Emma Ahlqvist, Denis Rybin, John R Petrie, Mary E Travers, Nabila Bouatia-Naji, Antigone S Dimas, Alexandra Nica, Eleanor Wheeler, Han Chen, Benjamin F Voight, Jalal Taneera, Stavroula Kanoni, John F Peden, Fabiola Turrini, Stefan Gustafsson, Carina Zabena, Peter Almgren, David J P Barker, Daniel Barnes, Elaine M Dennison, Johan G Eriksson, Per Eriksson, Elodie Eury, Lasse Folkersen, Caroline S Fox, Timothy M Frayling, Anuj Goel, Harvest F Gu, Momoko Horikoshi, Bo Isomaa, Anne U Jackson, Karen A Jameson, Eero Kajantie, Julie Kerr-Conte, Teemu Kuulasmaa, Johanna Kuusisto, Ruth J F Loos, Jian'an Luan, Konstantinos Makrilakis, Alisa K Manning, María Teresa Martínez-Larrad, Narisu Narisu, Maria Nastase Mannila, John Ohrvik, Clive Osmond, Laura Pascoe, Felicity Payne, Avan A Sayer, Bengt Sennblad, Angela Silveira, Alena Stančáková, Kathy Stirrups, Amy J Swift, Ann-Christine Syvänen, Tiinamaija Tuomi, Ferdinand M van 't Hooft, Mark Walker, Michael N Weedon, Weijia Xie, Björn Zethelius, , Halit Ongen, Anders Malarstig, Jemma C Hopewell, Danish Saleheen, John Chambers, Sarah Parish, John Danesh, Jaspal Kooner, Claes-Göran Ostenson, Lars Lind, Cyrus C Cooper, Manuel Serrano-Ríos, Ele Ferrannini, Tom J Forsen, Robert Clarke, Maria Grazia Franzosi, Udo Seedorf, Hugh Watkins, Philippe Froguel, Paul Johnson, Panos Deloukas, Francis S Collins, Markku Laakso, Emmanouil T Dermitzakis, Michael Boehnke, Mark I McCarthy, Nicholas J Wareham, Leif Groop, François Pattou, Anna L Gloyn, George V Dedoussis, Valeriya Lyssenko, James B Meigs, Inês Barroso, Richard M Watanabe, Erik Ingelsson, Claudia Langenberg, Anders Hamsten, Jose C Florez.
Diabetes
PUBLISHED: 08-26-2011
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Proinsulin is a precursor of mature insulin and C-peptide. Higher circulating proinsulin levels are associated with impaired ?-cell function, raised glucose levels, insulin resistance, and type 2 diabetes (T2D). Studies of the insulin processing pathway could provide new insights about T2D pathophysiology.
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JoVE Visualize is a tool created to match the last 5 years of PubMed publications to methods in JoVE's video library.

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