305 research outputs found

    Development of a Web-based Resident Profiling Tool to Support Training in Practice-based Learning and Improvement

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    Multiple factors are driving residency programs to explicitly address practice-based learning and improvement (PBLI), yet few information systems exist to facilitate such training. We developed, implemented, and evaluated a Web-based tool that provides Internal Medicine residents at the University of Virginia Health System with population-based reports about their ambulatory clinical experiences. Residents use Systems and Practice Analysis for Resident Competencies (SPARC) to identify potential areas for practice improvement. Thirty-three (65%) of 51 residents completed a survey assessing SPARC’s usefulness, with 94% agreeing that it was a useful educational tool. Twenty-six residents (51%) completed a before–after study indicating increased agreement (5-point Likert scale, with 5=strongly agree) with statements regarding confidence in ability to access population-based data about chronic disease management (mean [SD] 2.5 [1.2] vs. 4.5 [0.5], p < .001, sign test) and information comparing their practice style to that of their peers (2.2 [1.2] vs. 4.6 [0.5], p < .001)

    Compared to placebo, long-term antibiotics resolve otitis media with effusion (OME) and prevent acute otitis media with perforation (AOMwiP) in a high-risk population: A randomized controlled trial

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    © 2008 Leach et al; licensee BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.Background : For children at high risk of chronic suppurative otitis media (CSOM), strategies to prevent acute otitis media with perforation (AOMwiP) may reduce progression to CSOM. Methods : In a double blind study in northern Australia, 103 Aboriginal infants with first detection of OME were randomised to receive either amoxicillin (50 mg/kg/d BD) or placebo for 24 weeks, or until bilateral aerated middle ears were diagnosed at two successive monthly examinations (success). Standardised clinical assessments and international standards for microbiology were used. Results : Five of 52 infants in the amoxicillin group and none of 51 infants in the placebo group achieved success at the end of therapy (Risk Difference = 9.6% [95% confidence interval 1.6,17.6]). Amoxicillin significantly reduced the proportion of children with i) perforation at the end of therapy (27% to 12% RD = -16% [-31,-1]), ii) recurrent perforation during therapy (18% to 4% RD = -14% [-25,-2]), and iii) reduced the proportion of examinations with a diagnosis of perforation during therapy (20% to 8% adjusted risk ratio 0.36 [0.15,0.83] p = 0.017). During therapy, the proportion of examinations with penicillin non-susceptible (MIC > 0.1 microg/ml) pneumococci was not significantly different between the amoxicillin group (34%) and the placebo group (40%). Beta-lactamase positive non-capsular H. influenzae (NCHi) were uncommon during therapy but more frequent in the amoxicillin group (10%) than placebo (5%). Conclusion : Aboriginal infants receiving continuous amoxicillin had more normal ears, fewer perforations, and less pneumococcal carriage. There was no statistically significant increase in resistant pneumococci or NCHi in amoxicillin children compared to placebo children who received regular paediatric care and antibiotic treatment for symptomatic illnesses

    Assessing the Quality of Clinical Teachers: A Systematic Review of Content and Quality of Questionnaires for Assessing Clinical Teachers

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    BACKGROUND: Learning in a clinical environment differs from formal educational settings and provides specific challenges for clinicians who are teachers. Instruments that reflect these challenges are needed to identify the strengths and weaknesses of clinical teachers. OBJECTIVE: To systematically review the content, validity, and aims of questionnaires used to assess clinical teachers. DATA SOURCES: MEDLINE, EMBASE, PsycINFO and ERIC from 1976 up to March 2010. REVIEW METHODS: The searches revealed 54 papers on 32 instruments. Data from these papers were documented by independent researchers, using a structured format that included content of the instrument, validation methods, aims of the instrument, and its setting. Results : Aspects covered by the instruments predominantly concerned the use of teaching strategies (included in 30 instruments), supporter role (29), role modeling (27), and feedback (26). Providing opportunities for clinical learning activities was included in 13 instruments. Most studies referred to literature on good clinical teaching, although they failed to provide a clear description of what constitutes a good clinical teacher. Instrument length varied from 1 to 58 items. Except for two instruments, all had to be completed by clerks/residents. Instruments served to provide formative feedback ( instruments) but were also used for resource allocation, promotion, and annual performance review (14 instruments). All but two studies reported on internal consistency and/or reliability; other aspects of validity were examined less frequently. CONCLUSIONS: No instrument covered all relevant aspects of clinical teaching comprehensively. Validation of the instruments was often limited to assessment of internal consistency and reliability. Available instruments for assessing clinical teachers should be used carefully, especially for consequential decisions. There is a need for more valid comprehensive instruments

    Transport of Pb and Zn by carboxylate complexes in basinal ore fluids and related petroleum-field brines at 100°C: the influence of pH and oxygen fugacity

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    It is well established through field observations, experiments, and chemical models that oxidation (redox) state and pH exert a strong influence on the speciation of dissolved components and the solubility of minerals in hydrothermal fluids. log [Image: see text] –pH diagrams were used to depict the influence of oxygen fugacity and pH on monocarboxylate- and dicarboxylate-transport of Pb and Zn in low-temperature (100°C) hydrothermal ore fluids that are related to diagenetic processes in deep sedimentary basins, and allow a first-order comparison of Pb and Zn transport among proposed model fluids for Mississippi Valley-type (MVT) and red-bed related base metal (RBRBM) deposits in terms of their approximate pH and [Image: see text] conditions. To construct these diagrams, total Pb and Zn concentrations and Pb and Zn speciation were calculated as a function of log [Image: see text] and pH for a composite ore-brine with concentrations of major elements, total sulfur, and total carbonate that approximate the composition of MVT and RBRBM model ore fluids and modern basinal brines. In addition to acetate and malonate complexation, complexes involving the ligands Cl(-), HS(-), H(2)S, and OH(- )were included in the model of calculated total metal concentration and metal speciation. Also, in the model, Zn and Pb are competing with the common-rock forming metals Ca, Mg, Na, Fe, and Al for the same ligands. Calculated total Pb concentration and calculated total Zn concentration are constrained by galena and sphalerite solubility, respectively. Isopleths, in log [Image: see text] –pH space, of the concentration of Pb and concentration of Zn in carboxylate (acetate + malonate) complexes illustrate that the oxidized model fluids of T. H. Giordano (in Organic Acids in Geological Processes, ed. E. D. Pittman and M. D. Lewan, Springer-Verlag, New York, 1994, pp. 319–354) and G. M. Anderson (Econ. Geol., 1975, 70, 937–942) are capable of transporting sufficient amounts of Pb (up to 10 ppm) and Zn (up to 100 ppm) in the form of carboxylate complexes to form economic deposits of these metals. On the other hand, the reduced ore fluid models of D. A. Sverjensky (Econ. Geol., 1984, 79, 23–37) and T. H. Giordano and H. L. Barnes (Econ. Geol., 1981, 76, 2200–2211) can at best transport amounts of Pb and Zn, as carboxylate complexes, that are many orders of magnitude below the 1 to 10 ppm minimum required to form economic deposits. Lead and zinc speciation (mol% of total Pb or Zn) in the model ore fluid was calculated at specific log [Image: see text] –pH conditions along the 100, 0.01, and 0.001 ppm total Pb and total Zn isopleths. Along the 100 ppm isopleth conditions are oxidized (∑SO(4 )>> ∑H(2)S) with Pb and Zn predominantly in the form of chloride complexes under acid to mildly alkaline conditions (pH from 3 to approximately 7.5), while hydroxide complexes dominate Pb and Zn speciation under more alkaline conditions. Sulfide complexes are insignificant under these oxidized conditions. For more reduced conditions along the 0.01 and 0.001 ppm isopleths chloride complexes dominate Pb and Zn speciation in the SO(4)(2- )field and near the SO(4)(2-)-reduced sulfur boundary from pH = 4 to approximately 7.5, while hydroxide complexes dominate Pb and Zn speciation under alkaline conditions above pH = 7.5 in the SO(4)(2- )field. In the most reduced fluids (∑H(2)S >> ∑SO(4)) along the 0.01 and 0.001 isopleths, sulfide complexes account for almost 100% of the Pb and Zn in the model fluid. Acetate (monocarboxylate) complexation is significant only under conditions of chloride and hydroxide complex dominance and its effect is maximized in the pH range 5 to 7, where it complexes 2 to 2.6% of the total Pb and 1 to 1.25% of the total Zn. Malonate (dicarboxylate) complexes are insignificant along all isopleths. The speciation results from this study show that deep formation waters characterized by temperatures near 100°C, high oxidation states and ∑H(2)S < 0.03 mg L(-1 )([Image: see text] < 10(-6)), high chlorinities (~ 100000 mg L(-1)), and high but reasonable concentrations of carboxylate anions can mobilize up to 3% of the total Pb and up to 1.3% of the total Zn as carboxylate complexes. Furthermore, these percentages, under the most favorable conditions, correspond to approximately 1 to 100 ppm of these metals in solution; concentrations that are adequate to form economic deposits of these metals. However, the field evidence suggests that all of these optimum conditions for carboxylate complexation are rarely met at the same time. A comparison of the composite ore fluid compositions from this study and modern brine data shows that the ore brines, corresponding to log [Image: see text] –pH conditions based on the Anderson (1975) and Giordano (1994) model fluids, are similar in many respects to modern, high trace-metal petroleum-field brines. The principal differences between modern high trace-metal brines and the composite ore fluids of Anderson (1975) and Giordano (1994) relate to their carboxylate anion content. The reported concentrations of monocarboxylate anions (∑monocbx) and dicarboxylate anions (Edicbx) in high trace-metal petroleum-field brines (< 1 to 300 mg L(-1 )and < 1 mg L(-1), respectively) are significantly lower than the concentrations assumed in the modelled brines of this study (∑monocbx = 7 700 mg L(-1 )and ∑dicbx = 300 mg L(-1)). There are also major differences in the corresponding total chloride to carboxylate ratio (∑m(Cl)/∑m(cbx)) and monocarboxylate to dicarboxylate ratio (∑m(monocbx)/∑m(dicbx)). Modern high trace-metal brines have much higher ∑m(Cl)/∑m(cbx )values and, therefore, the contribution of carboxylate complexes to the total Pb and Zn content in these modern brines is likely to be significantly less than the 1 to 3 percent for the composite ore fluids of Anderson (1975) and Giordano (1994). The composite ore-brine based on the Giordano and Barnes (1981) MVT ore fluid is comparable to the high salinity (> 170 000 mg L(-1 )TDS) subset of modern brines characterized by low trace-metal content and high total reduced sulfur (∑H(2)S). A comparison of the Sverjensky (1984) composite ore-brine with modern petroleum-field brines in terms of ∑H(2)S and Zn content, reveals that this ore fluid corresponds to a "border-type" brine, between modern high trace-metal brines and those with low trace-metal content and high ∑H(2)S. A brine of this type is characterized by values of ∑H(2)S, ∑Zn, and/or ∑Pb within or near the 1 to 10 mg L(-1 )range. Based on brine-composition data from numerous references cited in this paper, border-type brines do exist but are rare. The model results and field evidence presented in this study are consistent with other chemical simulation studies of carboxylate complexation in modern petroleum-field brines. Thus, it appears that carboxylate complexation plays a minor, if not insignificant, role as a transport mechanism for Pb and Zn in high salinity Na–Cl and Na–Ca–Cl basinal brines and related ore fluids

    GWAS of Follicular Lymphoma Reveals Allelic Heterogeneity at 6p21.32 and Suggests Shared Genetic Susceptibility with Diffuse Large B-cell Lymphoma

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    Non-Hodgkin lymphoma (NHL) represents a diverse group of hematological malignancies, of which follicular lymphoma (FL) is a prevalent subtype. A previous genome-wide association study has established a marker, rs10484561 in the human leukocyte antigen (HLA) class II region on 6p21.32 associated with increased FL risk. Here, in a three-stage genome-wide association study, starting with a genome-wide scan of 379 FL cases and 791 controls followed by validation in 1,049 cases and 5,790 controls, we identified a second independent FL–associated locus on 6p21.32, rs2647012 (ORcombined = 0.64, Pcombined = 2×10−21) located 962 bp away from rs10484561 (r2<0.1 in controls). After mutual adjustment, the associations at the two SNPs remained genome-wide significant (rs2647012:ORadjusted = 0.70, Padjusted = 4×10−12; rs10484561:ORadjusted = 1.64, Padjusted = 5×10−15). Haplotype and coalescence analyses indicated that rs2647012 arose on an evolutionarily distinct haplotype from that of rs10484561 and tags a novel allele with an opposite (protective) effect on FL risk. Moreover, in a follow-up analysis of the top 6 FL–associated SNPs in 4,449 cases of other NHL subtypes, rs10484561 was associated with risk of diffuse large B-cell lymphoma (ORcombined = 1.36, Pcombined = 1.4×10−7). Our results reveal the presence of allelic heterogeneity within the HLA class II region influencing FL susceptibility and indicate a possible shared genetic etiology with diffuse large B-cell lymphoma. These findings suggest that the HLA class II region plays a complex yet important role in NHL

    A Variable Region within the Genome of Streptococcus pneumoniae Contributes to Strain-Strain Variation in Virulence

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    The bacterial factors responsible for the variation in invasive potential between different clones and serotypes of Streptococcus pneumoniae are largely unknown. Therefore, the isolation of rare serotype 1 carriage strains in Indigenous Australian communities provided a unique opportunity to compare the genomes of non-invasive and invasive isolates of the same serotype in order to identify such factors. The human virulence status of non-invasive, intermediately virulent and highly virulent serotype 1 isolates was reflected in mice and showed that whilst both human non-invasive and highly virulent isolates were able to colonize the murine nasopharynx equally, only the human highly virulent isolates were able to invade and survive in the murine lungs and blood. Genomic sequencing comparisons between these isolates identified 8 regions >1 kb in size that were specific to only the highly virulent isolates, and included a version of the pneumococcal pathogenicity island 1 variable region (PPI-1v), phage-associated adherence factors, transporters and metabolic enzymes. In particular, a phage-associated endolysin, a putative iron/lead permease and an operon within PPI-1v exhibited niche-specific changes in expression that suggest important roles for these genes in the lungs and blood. Moreover, in vivo competition between pneumococci carrying PPI-1v derivatives representing the two identified versions of the region showed that the version of PPI-1v in the highly virulent isolates was more competitive than the version from the less virulent isolates in the nasopharyngeal tissue, blood and lungs. This study is the first to perform genomic comparisons between serotype 1 isolates with distinct virulence profiles that correlate between mice and humans, and has highlighted the important role that hypervariable genomic loci, such as PPI-1v, play in pneumococcal disease. The findings of this study have important implications for understanding the processes that drive progression from colonization to invasive disease and will help direct the development of novel therapeutic strategies

    Genomic Organization of H2Av Containing Nucleosomes in Drosophila Heterochromatin

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    H2Av is a versatile histone variant that plays both positive and negative roles in transcription, DNA repair, and chromatin structure in Drosophila. H2Av, and its broader homolog H2A.Z, tend to be enriched toward 5′ ends of genes, and exist in both euchromatin and heterochromatin. Its organization around euchromatin genes and other features have been described in many eukaryotic model organisms. However, less is known about H2Av nucleosome organization in heterochromatin. Here we report the properties and organization of individual H2Av nucleosomes around genes and transposable elements located in Drosophila heterochromatic regions. We compare the similarity and differences with that found in euchromatic regions. Our analyses suggest that nucleosomes are intrinsically positioned on inverted repeats of DNA transposable elements such as those related to the “1360” element, but are not intrinsically positioned on retrotransposon-related elements
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