OBJECTIVES: To systematically review studies designed to increase advance directive completion in the primary care setting and employ meta‐analytic techniques to quantify their effects.
DESIGN: ...Extensive bibliographic searches of English‐language literature published from January 1991 through July 2005 were conducted. Investigators ed prespecified information (e.g., design, study duration, types of interventions employed) and advance directive completion rates for intervention and control arms in each investigation and calculated absolute rate differences (i.e., difference in completion rates between the two groups) for each study. Individual study and pooled‐effect sizes were also calculated, along with 95% confidence intervals (CIs).
SETTING: Literature review.
RESULTS: Eighteen studies were retained in the final sample. Most studies employed multimodal interventions. The most common approach consisted of educational materials directed at patients (through mailing or at visit) coupled with a patient–healthcare provider interaction in a group or individual setting (n=7). Absolute differences in completion rates varied from a high of 44% (favors intervention) to a low of –2% (favors control). Effect sizes could be calculated for 15 of the 18 studies. The pooled effect size was 0.50 (95% CI=0.17–0.83), indicating a moderate overall effect in favor of the intervention.
CONCLUSION: The majority of studies demonstrated statistically significant effects associated with the advance directive intervention. The most successful interventions incorporated direct patient–healthcare professional interactions over multiple visits. Passive education of patients using written materials (without direct counseling) was a relatively ineffective method for increasing advance directive completion rates in the primary care setting.
Point‐of‐care (POC) diagnostic devices have been predicted to provide a boon in health care especially in the diagnosis and detection of diseases. POC devices have been found to have many advantages ...like a rapid and precise response, portability, low cost, and non‐requirement of specialized equipment. The major objective of a POC diagnostic research is to develop a chip‐based, self‐containing miniaturized device that can be used to examine different analytes in complex samples. Further, the integration of microfluidics (MF) with advanced biosensor technologies is likely to result in improved POC diagnostics. This paper presents the overview of the different materials (glass, silicon, polymer, paper) and techniques for the fabrication of MF based POC devices along with their wide range of biosensor applications. Besides this, the authors have presented in brief the challenges that MF is currently facing along with possible solutions that may result in the availability of the accessible, reliable, and cost‐efficient technology. The development of these devices requires the combination of developed MF components into POC devices that are user‐friendly, sensitive, stable, accurate, low cost, and minimally invasive. These MF based POC devices have tremendous potential in providing improved healthcare including easy monitoring, early detection of disease, and increased personalization.
Overview on the latest advancements in the field of microfludics based point‐of‐care devices, that can be integrated with the biorecognition elements, for miniaturization and ease of multiplexing.
Understanding the circumstances under which drivers and passengers are more likely to be killed or more severely injured in an automobile accident can help improve the overall driving safety ...situation. Factors that affect the risk of increased injury of occupants in the event of an automotive accident include demographic or behavioral characteristics of the person, environmental factors and roadway conditions at the time of the accident occurrence, technical characteristics of the vehicle itself, among others. This study uses a series of artificial neural networks to model the potentially non-linear relationships between the injury severity levels and crash-related factors. It then conducts sensitivity analysis on the trained neural network models to identify the prioritized importance of crash-related factors as they apply to different injury severity levels. In the process, the problem of five-class prediction is decomposed into a set of binary prediction models (using a nationally representative sample of 30
358 police-recorded crash reports) in order to obtain the granularity of information needed to identify the “true” cause and effect relationships between the crash-related factors and different levels of injury severity. The results, mostly validated by the findings of previous studies, provide insight into the changing importance of crash factors with the changing injury severity levels.
Thromboembolic events (TE) are the most common complications of myeloproliferative neoplasms (MPN). Clinical parameters, including patient age and mutation status, are used to risk-stratify patients ...with MPN, but a true biomarker of TE risk is lacking. Protein disulfide isomerase (PDI), an endoplasmic reticulum protein vital for protein folding, also possesses essential extracellular functions, including regulation of thrombus formation. Pharmacologic PDI inhibition prevents thrombus formation, but whether pathologic increases in PDI increase TE risk remains unknown.
We evaluated the association of plasma PDI levels and risk of TE in a cohort of patients with MPN with established diagnosis of polycythemia vera (PV) or essential thrombocythemia (ET), compared with healthy controls. Plasma PDI was measured at enrollment and subjects followed prospectively for development of TE.
A subset of patients, primarily those with
-mutated MPN, had significantly elevated plasma PDI levels as compared with controls. Plasma PDI was functionally active. There was no association between PDI levels and clinical parameters typically used to risk-stratify patients with MPN. The risk of TE was 8-fold greater in those with PDI levels above 2.5 ng/mL. Circulating endothelial cells from
-mutated MPN patients, but not platelets, demonstrated augmented PDI release, suggesting endothelial activation as a source of increased plasma PDI in MPN.
The observed association between plasma PDI levels and increased risk of TE in patients with
mutated MPN has both prognostic and therapeutic implications.
N132D is the brightest gamma-ray supernova remnant (SNR) in the Large Magellanic Cloud (LMC). We carried out 12CO(J = 1-0, 3-2) observations toward the SNR using the Atacama Large ...Millimeter/submillimeter Array (ALMA) and Atacama Submillimeter Telescope Experiment. We find diffuse CO emission not only at the southern edge of the SNR as previously known, but also inside the X-ray shell. We spatially resolved nine molecular clouds using ALMA with an angular resolution of 5″, corresponding to a spatial resolution of ∼1 pc at the distance of the LMC. Typical cloud sizes and masses are ∼2.0 pc and ∼100 M , respectively. High intensity ratios of CO J = 3-2/1-0 > 1.5 are seen toward the molecular clouds, indicating that shock heating has occurred. Spatially resolved X-ray spectroscopy reveals that thermal X-rays in the center of N132D are produced not only behind a molecular cloud but also in front of it. Considering the absence of a thermal component associated with the forward shock toward one molecular cloud located along the line of sight to the center of the remnant, this suggests that this particular cloud is engulfed by shock waves and is positioned on the near side of the remnant. If the hadronic process is the dominant contributor to the gamma-ray emission, the shock-engulfed clouds play a role as targets for cosmic rays. We estimate the total energy of cosmic-ray protons accelerated in N132D to be ∼0.5-3.8 × 1049 erg as a conservative lower limit, which is similar to that observed in Galactic gamma-ray SNRs.
The solar-assisted oxidation of water is an essential half reaction for achieving a complete cycle of water splitting. The search of efficient photoanodes that can absorb light in the visible range ...is of paramount importance to enable cost-effective solar energy-conversion systems. Here, we demonstrate that atomically thin layers of MoS2 and WS2 can oxidize water to O2 under incident light. Thin films of solution-processed MoS2 and WS2 nanosheets display n-type positive photocurrent densities of 0.45 mA cm–2 and O2 evolution under simulated solar irradiation. WS2 is significantly more efficient than MoS2; however, bulk heterojunctions (B-HJs) of MoS2 and WS2 nanosheets results in a 10-fold increase in incident-photon-to-current-efficiency, compared to the individual constituents. This proves that charge carrier lifetime is tailorable in atomically thin crystals by creating heterojunctions of different compositions and architectures. Our results suggest that the MoS2 and WS2 nanosheets and their B-HJ blend are interesting photocatalytic systems for water oxidation, which can be coupled with different reduction processes for solar-fuel production.
von Willebrand factor (VWF) is an essential hemostatic protein that is synthesized in endothelial cells and stored in Weibel-Palade bodies (WPBs). Understanding the mechanisms underlying WPB ...biogenesis and exocytosis could enable therapeutic modulation of endogenous VWF, yet optimal targets for modulating VWF release have not been established. Because biogenesis of lysosomal related organelle-2 (BLOC-2) functions in the biogenesis of platelet dense granules and melanosomes, which like WPBs are lysosome-related organelles, we hypothesized that BLOC-2–dependent endolysosomal trafficking is essential for WPB biogenesis and sought to identify BLOC-2–interacting proteins. Depletion of BLOC-2 caused misdirection of cargo-carrying transport tubules from endosomes, resulting in immature WPBs that lack endosomal input. Immunoprecipitation of BLOC-2 identified the exocyst complex as a binding partner. Depletion of the exocyst complex phenocopied BLOC-2 depletion, resulting in immature WPBs. Furthermore, releasates of immature WPBs from either BLOC-2 or exocyst-depleted endothelial cells lacked high-molecular weight (HMW) forms of VWF, demonstrating the importance of BLOC-2/exocyst-mediated endosomal input during VWF maturation. However, BLOC-2 and exocyst showed very different effects on VWF release. Although BLOC-2 depletion impaired exocytosis, exocyst depletion augmented WPB exocytosis, indicating that it acts as a clamp. Exposure of endothelial cells to a small molecule inhibitor of exocyst, Endosidin2, reversibly augmented secretion of mature WPBs containing HMW forms of VWF. These studies show that, although BLOC-2 and exocyst cooperate in WPB formation, only exocyst serves to clamp WPB release. Exocyst function in VWF maturation and release are separable, a feature that can be exploited to enhance VWF release.
•Exocyst interacts with BLOC-2 in the delivery of endosomal cargo to maturing Weibel Palade bodies essential for VWF multimerization.•Exocyst serves as a clamp, impeding VWF exocytosis, which can be reversibly inhibited to facilitate VWF release.
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This study was designed to compare costs of adjuvant radiation versus observation in the management of early-stage testicular seminoma after inguinal orchiectomy.
A line-by-line inspection of the ...charges generated during a course of adjuvant pelvic and paraaortic radiotherapy and of three cycles of bleomycin, etoposide, and platinum salvage chemotherapy was performed for five patients who received irradiation and five patients who received salvage chemotherapy. The average charge for either treatment was then calculated. Only those charges directly associated with the diagnosis of seminoma were included in the analysis. Follow-up charges were also generated from the patients' billing records. The optimum follow-up regimen for either management option was derived from a synthesis of the international literature. A 5% rate of failure was assumed if adjuvant irradiation was administered, and a 15% rate of failure was assumed if observation was the option chosen. Charges were truncated at 5 years.
The total charge generated over 5 years based on following a policy of observation is $27,223 per patient versus $19,557 if the option of adjuvant irradiation in chosen. Using University of Wisconsin institutional reimbursement rates, the estimated costs were $20,487 and $14,722 for the option of observation and adjuvant radiation, respectively. The cost equivalence point between the two options occurs at 2.5 years, when the initial cost of adjuvant radiotherapy is matched by the cost generated during the period of observation. The maximum cost difference is achieved by 5 years.
Following a policy of observation postorchiectomy for early-stage testicular seminoma generates 39% more medical costs per patient over a 5-year follow-up period than does following the standard policy of adjuvant irradiation to the pelvic and paraaortic regions, with no reported difference in outcome.
M1 activation of macrophages promotes inflammation and immunity to intracellular pathogens, whereas M2 macrophage activation promotes resolution of inflammation, wound healing, and tumor growth. ...These divergent phenotypes are characterized, in part, by the expression of inducible NO synthase and arginase I (Arg1) in M1 versus M2 activated macrophages, respectively. In this study, we demonstrate that the Ron receptor tyrosine kinase tips the balance of macrophage activation by attenuating the M1 phenotype while promoting expression of Arg1 through a Stat6-independent mechanism. Induction of the Arg1 promoter by Ron is mediated by an AP-1 site located 433 bp upstream of the transcription start site. Treatment of primary macrophages with macrophage stimulating protein, the ligand for Ron, induces potent MAPK activation, upregulates Fos, and enhances binding of Fos to the AP-1 site in the Arg1 promoter. In vivo, Arg1 expression in tumor-associated macrophages (TAMs) from Ron(-/-) mice was significantly reduced compared with that in TAMs from control animals. Furthermore, we show that Ron is expressed specifically by Tie2-expressing macrophages, a TAM subset that exhibits a markedly skewed M2 and protumoral phenotype. Decreased Arg1 in TAMs from Ron(-/-) mice was associated with reduced syngeneic tumor growth in these animals. These findings indicate that Ron induces Arg1 expression in macrophages through a previously uncharacterized AP-1 site in the Arg1 promoter and that Ron could be therapeutically targeted in the tumor microenvironment to inhibit tumor growth by targeting expression of Arg1.
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