Evidence-based management: using serial firm trials to improve diabetes care quality

BACKGROUND: The design of delivery systems that can truly conduct continuous quality improvement (CQI) as a routine part of clinical care provision remains a vexing problem. The effectiveness of the "computerized firm system" approach to chronic disease CQI was examined, with diabetes as the focus of a 5-year case study. METHODS: A large family medical center had been divided into two parallel group practices for reasons of efficiency. These frontline structures (also known as primary care "firms") were supported to serially adapt and evaluate selected CQI interventions by first introducing process changes on one firm but not the other and comparing the groups. Because all the required longitudinal data were contained in a computerized repository, it was possible to conduct these controlled "firm trials" in a matter of months at low cost. RESULTS: During a 3-year period, implementation of point-of-service reminders and a pharmacist out-reach program increased recommended glycohemoglobin (HbA1c) testing by 50% (p = 0.02) and reduced the number of diabetic patients inadequately controlled by 43% (p < 0.01). Following this outcome improvement, patients exhibited a 16% reduction in ambulatory visit rates (p = 0.04). The observed outcome improvement, however, was reversed during the subsequent 2 years, when staffing austerities forced by unrelated declines in clinic revenue caused the withdrawal of trial interventions. CONCLUSIONS: The processes and outcomes of diabetes care were improved, demonstrating that CQI and controlled trials are not mutually exclusive in moving toward the practice of evidence-based management. Health care systems can, by conducting serial firm trials, become learning organizations. CQI programs of all kinds will likely never flourish, however, until quality improvement and reimbursement mechanisms have become better aligned.     

Protection of normal cells from irradiation bystander effects by silica-flufenamic acid nanoparticles

The development of a myriad of nanoparticles types has opened new possibilities for the diagnostics and treatment of many diseases, especially for cancer. However, most of the researches done so far do not focus on the protection of normal cells surrounding a tumor from irradiation bystander effects that might lead to cancer recurrence. Gap-junctions are known to be involved in this process, which leads to genomic instability of neighboring normal cells, and flufenamic acid (FFA) is included in a new group of gap-junction blockers recently discovered. The present work explores the use of mesoporous silica nanoparticles MCM-41 functionalized with 3-Aminopropyltriethoxysilane (APTES) for anchoring the flufenamic acid for its prolonged and controlled release and protection from radiation bystander effects. MCM-41 and functionalized samples were structurally and chemically characterized with multiple techniques. The biocompatibility of all samples was tested in a live/dead assay performed in cultured MRC-5 and HeLa cells. HeLa cells cultured were exposed to 50?Gy of gamma-rays and the media transferred to fibroblast cells cultured separately. Our results show that MCM-41 and functionalized samples have high biocompatibility with MCR-5 and HeLa cells, and most importantly, the FFA delivered by these NPs was able to halt apoptosis, one of main bystander effects.     

直击劲爆演出现场

相信很多人都为摇滚现场演出的效果所震撼,何不拿起你的相机,把这激动人心的时刻定格下来,作为永久的纪念呢?我们英国的编辑Ed Godden前往摇滚圣地——普利茅斯展馆剧场,拍下了休克摇滚之父AliceCooper的狂野演出。     

Measuring knowledge transfer between fields of science

In this paper we report on the results of an exploratory study of knowledge exchange between disciplines and subfields of science, based on bibliometric methods. The goal of this analysis is twofold. Firstly, we consider knowledge exchange between disciplines at a global level, by analysing cross-disciplinary citations in journal articles, based on the world publication output in 1999. Among others a central position of the Basic Life Sciences within the Life Sciences and of Physics within the Exact Sciences is shown. Limitations of analyses of interdisciplinary impact at the journal level are discussed. A second topic is a discussion of measures which may be used to quantify the rate of knowledge transfer between fields and the importance of work in a given field or for other disciplines. Two measures are applied, which appear to be proper indicators of impact of research on other fields. These indicators of interdisciplinary impact may be applied at other institutional levels as well. This revised version was published online in August 2006 with corrections to the Cover Date.     

Wavelength dependence of irreversible photobleaching of dye-doped polymer waveguide materials

We report the irreversible bleaching characteristics of 4-(dicyanomethylene)-2-methyl-6-(p-dimethyl aminostyryl)-4H-pyran (DCM) doped into perfluorocyclobutene (PFCB) and a new material known as DH-6 doped into amorphous polycarbonate (APC) by a monochromatic bleaching source. The wavelength dependent rate constants for the irreversible bleaching process are found, and the experimental bleaching characteristics are compared to the theoretical bleaching characteristics determined from a kinetic model of the bleaching process.     

Correlation coefficient mapping in fluorescence spectroscopy: tissue classification for cancer detection

Correlation coefficient mapping has been applied to intrinsic fluorescence spectra of colonic tissue for the purpose of cancer diagnosis. Fluorescence emission spectra were collected of 57 colonic tissue sites in a range of 4 physiological conditions: normal (29), hyperplastic (2), adenomatous (5), and cancerous tissues (21). The sample-sample correlation was used to examine the ability of correlation coefficient mapping to determine tissue disease state. The correlation coefficient map indicates two main categories of samples. These categories were found to relate to disease states of the tissue. Sensitivity, selectivity, predictive value positive, and predictive value negative for differentiation between normal tissue and all other categories were all above 92%. This was found to be similar to, or higher than, tissue classification using existing methods of data reduction. Wavelength-wavelength correlation among the samples highlights areas of importance for tissue classification. The two-dimensional correlation map reveals absorption by NADH and hemoglobin in the samples as negative correlation, an effect not obvious from the one-dimensional fluorescence spectra alone. The integrity of tissue was examined in a time series of spectra of a single tissue sample taken after tissue resection. The wavelength-wavelength correlation coefficient map shows the areas of significance for each fluorophore and their relation to each other. NADH displays negative correlation to collagen and FAD, from the absorption of emission or fluorescence resonance energy transfer. The wavelength-wavelength correlation map for the decay set also clearly shows that there are only three fluorophores of importance in the samples, by the well-defined pattern of the map. The sample-sample correlation coefficient map reveals the changes over time and their impact on tissue classification. Correlation coefficient mapping proves to be an effective method for sample classification and cancer detection.     

Acid Active Receptor‐Specific Peptide Ligand for In Vivo Tumor‐Targeted Delivery

Targeting therapy of tumors in their early stages is crucial to increase the survival rate of cancer patients. Currently most drug‐delivery systems target the neoplasia through the tumor‐associated receptors overexpressed on the cancer cell membrane. However, the expression of these receptors on normal cells and tissues is inevitable, which leads to unwanted accumulation and side effects. Characteristics of the tumor microenvironment, such as acidosis, are pervasive in almost all solid tumors and can be easily accessed. It is shown that the different extracellular pH value can be used to activate/inactivate the receptor‐mediated endocytosis on tumor/normal cells. This idea is implemented by conjugating a shielding molecule at the terminus of a receptor‐specific ligand via a pH‐sensitive hydrazone bond. The acid‐activated detachment of the shielding molecule and enhanced tumor/background accumulation ratio are demonstrated. These results suggest that acid active receptor‐specific peptide ligand‐modified tumor‐targeting delivery systems have potential use in the treatment of tumors.     

Role of nitrogen lewis basicity in boronate affinity chromatography of nucleosides

Urinary modified nucleosides have a potential role as cancer biomarkers, and most of the methods used in their study have utilized low-pressure phenylboronate affinity chromatography materials for the purification of the cis-diol-containing nucleosides. In this study, a boronate HPLC column was surprisingly shown not to trap the nucleosides as would be expected from experience with the classic Affigel 601 resin but showed only partial selectivity toward cis-diol groups while other groups exhibited better retention. In aprotic conditions, trapping of nucleosides was possible; however, the selectivity toward cis-diol-containing compounds was lost with the Lewis basicity of available nitrogens being the main determinant of retention. The experimental findings are compared to and confirmed by DFT calculations.     

Highy oblique impacts into thick and thin targets

Hypervelocity impact (HVI) tests have been conducted at the JSC Hypervelocity Impact Test Facility (HIT-F) with aluminum projectiles impacting semi-infinite (thick) and thin aluminum plates (with plate thickness to projectile diameter ratios of 6.4 and 0.14, respectively) at impact angles ranging from normal to the plate (0°) to highly oblique (88°). The targets were impacted by solid homogeneous aluminum spheres from 1 mm to 3.6 mm diameter. Results of the HVI tests were not unusual up to 65°, where impact damage is characterized as smooth craters and holes that become progressively elliptical and distended along the projectile flight path. Above 65° angles, however, a transition occurs to an irregularly shaped hole in thin materials and rough bottomed crater in thick targets. Above 80°, multiple damage sites in the targets were formed with the damage areas separated by variable distances of undamaged target surface. Analytical and numerical simulations of the impact process at oblique angles above 65° demonstrates that shock compression and release of the projectile into multiple fragments occurs before the projectile fully engages the target. The resulting projectile fragments are then responsible for the multiple impact sites observed on the targets.     

Pericardial tamponade as the first manifestation of dermatopolymyositis

Pericardial involvement in polymyositis and dermatomyositis (PM/DM) is rare, usually asymptomatic and exceptionally part of the initial presentation. We describe a 37-year-old patient hospitalized for overt acute pericarditis, revealing dermatomyositis, which to our knowledge has not been previously reported. Pericardial puncture relieved the patient. The pericardial fluid was citrine yellow, exsudative, and mainly contained lymphocytes. Search for LE cells and anti-DNA antibodies was negative, whereas the antinuclear antibodies and the rheumatoid factor were present in the pericardial fluid. A biopsy of the pericardium showed a non-specific chronic inflammatory state and the search for an etiology was negative. There was no sign of tuberculosis, systemic lupus, nor neoplasia. Moreover bacteriological cultures and HIV serology were negative. After pericardiostomy associated with corticosteroid therapy at the dose of 1 mg/kg/day, outcome was good with a resolution of the pericarditis confirmed at one-year follow-up. Since pericardial tamponade, even though rare, may be fatal in a patient with dermatomyositis, we emphasize that a two dimensional echocardiographic study should be performed in all patient presenting with dermatopolymyositis.