2,103 research outputs found

    Targeting kidney mesangium by nanoparticles of defined size

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    Nanoparticles are being investigated for numerous medical applications and are showing potential as an emerging class of carriers for drug delivery. Investigations on how the physicochemical properties (e.g., size, surface charge, shape, and density of targeting ligands) of nanoparticles enable their ability to overcome biological barriers and reach designated cellular destinations in sufficient amounts to elicit biological efficacy are of interest. Despite proven success in nanoparticle accumulation at cellular locations and occurrence of downstream therapeutic effects (e.g., target gene inhibition) in a selected few organs such as tumor and liver, reports on effective delivery of engineered nanoparticles to other organs still remain scarce. Here, we show that nanoparticles of ~75 ± 25-nm diameters target the mesangium of the kidney. These data show the effects of particle diameter on targeting the mesangium of the kidney. Because many diseases originate from this area of the kidney, our findings establish design criteria for constructing nanoparticle-based therapeutics for targeting diseases that involve the mesangium of the kidney

    Accuracy and reliability of injury coding in the national Dutch Trauma Registry

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    Objective: Injury coding is well known for lack of completeness and accuracy. The objective of this study was to perform a nationwide assessment of accuracy and reliability on Abbreviated Injury Scale (AIS) coding by Dutch Trauma Registry (DTR) coders and to determine the effect on Injury Severity Score (ISS). Additionally, the coders' characteristics were surveyed.Methods: Three fictional trauma cases were presented to all Dutch trauma coders in a nationwide survey (response rate 69%). The coders were asked to extract and code the cases' injuries according to the AIS manual (version 2005, update 2008). Reference standard was set by three highly experienced coders. Summary statistics were used to describe the registered AIS codes and ISS distribution. The primary outcome measures were accuracy of injury coding and inter-rater agreement on AIS codes. Secondary outcome measures were characteristics of coders: profession, work setting, experience in injury coding and training level in injury coding.Results: The total number of different AIS codes used to describe 14 separate injuries in the three cases was 89. Mean accuracy per AIS code was 42.2% (range 2.4-92.7%). Mean accuracy on number of AIS codes was 23%. Overall inter-rater agreement per AIS code was 49.1% (range 2.4-92.7%). The number of assigned AIS codes varied between 0 and 18 per injury. Twenty-seven percentage of injuries were overlooked. ISS was correctly scored in 42.4%. In 31.7%, the AIS coding of the two more complex cases led to incorrect classification of the patient as ISS = 16. Half (47%) of the coders had no (para)medical degree, 26% were working in level I trauma centers, 37% had less than 2 years of experience and 40% had no training in AIS coding.Conclusions: Accuracy of and inter-rater agreement on AIS injury scoring by DTR coders is limited. This may in part be due to the heterogeneous backgrounds and training levels of the coders. As a result of the inconsistent coding, the number of major trauma patients in the DTR may be over- or underestimated. Conclusions based on DTR data should therefore be drawn with caution.Trauma Surger

    The impact of constructive operating lease capitalisation on key accounting ratios

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    Current UK lease accounting regulation does not require operating leases to be capitalised in the accounts of lessees, although this is likely to change with the publication of FRS 5. This study conducts a prospective analysis of the effects of such a change. The potential magnitude of the impact of lease capitalisation upon individual users' decisions, market valuations, company cash flows, and managers' behaviour can be indicated by the effect on key accounting ratios, which are employed in decision-making and in financial contracts. The capitalised value of operating leases is estimated using a method similar to that suggested by Imhoff, Lipe and Wright (1991), adapted for the UK accounting and tax environment, and developed to incorporate company-specific assumptions. Results for 1994 for a random sample of 300 listed UK companies show that, on average, the unrecorded long-term liability represented 39% of reported long-term debt, while the unrecorded asset represented 6% of total assets. Capitalisation had a significant impact (at the 1% level) on six of the nine selected ratios (profit margin, return on assets, asset turnover, and three measures of gearing). Moreover, the Spearman rank correlation between each ratio before and after capitalisation revealed that the ranking of companies changed markedly for gearing measures in particular. There were significant inter-industry variations, with the services sector experiencing the greatest impact. An analysis of the impact of capitalisation over the five-year period from 1990 to 1994 showed that capitalisation had the greatest impact during the trough of the recession. Results were shown to be robust with respect to key assumptions of the capitalisation method. These findings contribute to the assessment of the economic consequences of a policy change requiring operating lease capitalisation. Significant changes in the magnitude of key accounting ratios and a major shift in company performance rankings suggest that interested parties' decisions and company cash flows are likely to be affected

    Hormone replacement therapy, mammography screening and changing age-specific incidence rates of breast cancer: an ecological study comparing two European populations

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    Background: In 2003, for the first time, US breast cancer incidence rates have fallen. Experts argue whether this is due to the reduced uptake of screening mammography or to lower use of Hormone Replacement Therapy (HRT). This study aims to disentangle the respective impact of screening and HRT on age-incidence rates and histology of breast cancer, by comparing two populations with comparably high levels of screening mammography, but with different prevalence of HRT. Methods: We included all invasive breast cancers recorded at the Geneva cancer registry (n=4,909) and the Netherlands Cancer Registry (n=152,428) between 1989-2003. We compared age-specific incidence rates and trends in histological subtyping between the two populations. Results: Between 1989-1991, incidence rates increased with age in both populations. In 2001-2003, women aged 60-64years showed highest incidence rates in Geneva, while in the Netherlands incidence rates continued to increase with age. The annual increase in ductal cancer incidence was similar in the Netherlands (2.3%) and Geneva (2.5%), but the annual increase in lobular cancer was sharper in Geneva (10%) than in the Netherlands (5%). Conclusion: The sharp differences in age distribution and histological subtyping of breast cancer between two European populations are not attributable to screening, since both populations have a high uptake of mammography screening. Since the prevalence of HRT use is very high in Geneva and rather low in the Netherlands, HRT may explain these discrepancies. However, other etiological factors and differences in histological assessment may also have played a rol

    Agreement on fixation of pediatric supracondylar humerus fractures

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    Background Pediatric supracondylar humerus fractures (pSCHFs) may be challenging injuries to treat because of the potential residual deformity. There is debate regarding the technical aspects of adequate closed reduction and crossed Kirschner wire (K-wire) fixation. Purpose Do surgeons have an agreement on the aspects of the fixation of pSCHFs? Methods Radiographs of 20 patients from a cohort of 154 patients with pSCHFs treated with closed reduction and crossed K-wire fixation were selected. Forty-four surgeons viewed the postoperative radiographs and diagnosed the presence or absence of technical flaws and made a recommendation for or against reoperation. An expert panel of three orthopedic and trauma surgeons provided a reference standard for technical factors. Furthermore, final outcome 2 years after trauma was assessed. Results There was limited agreement on potential technical flaws (ICC 0.15-0.28), radiographic measures of alignment (ICC for anterior humeral line and Baumann angle of 0.37 and 0.23 respectively), the quality of postoperative reduction, position of the elbow in cast, and recommendation for repeat surgery (ICCs between 0.23 and 0.40). Sensitivity and specificity for these questions ranged from 0.59 to 0.90. There was no correlation between the voted quality of postoperative reduction and loss of reduction or final function. Conclusions Surgeons have limited agreement on the quality of postoperative results in pSCHFs and the indication for reoperation. Reviewing postoperative radiographs may present a good learning opportunity and could help improve skills, but it is not a validated method for quality control and has to be seen in light of clinical outcome

    OT FE-Box Test Procedures

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    The OT FE readout requirements is the precise (~0.5 ns) and efficient drift time measurement at an occupancy of ~4% to ensure single hit resolution. The acquired achievement of such performance on an assembled FE-Box is verify through a final test performed using a special FE-Tester. In this note the test procedures are described

    Phase 3 Trial of 177Lu-Dotatate for Midgut Neuroendocrine Tumors

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    Background Patients with advanced midgut neuroendocrine tumors who have had disease progression during first-line somatostatin analogue therapy have limited therapeutic options. This randomized, controlled trial evaluated the efficacy and safety of lutetium-177 (177Lu)-Dotatate in patients with advanced, progressive, somatostatin-receptor-positive midgut neuroendocrine tumors. Methods We randomly assigned 229 patients who had well-differentiated, metastatic midgut neuroendocrine tumors to receive either 177Lu-Dotatate (116 patients) at a dose of 7.4 GBq every 8 weeks (four intravenous infusions, plus best supportive care including octreotide long-acting repeatable [LAR] administered intramuscularly at a dose of 30 mg) (177Lu-Dotatate group) or octreotide LAR alone (113 patients) administered intramuscularly at a dose of 60 mg every 4 weeks (control group). The primary end point was progression-free survival. Secondary end points included the objective response rate, overall survival, safety, and the side-effect profile. The final analysis of overall survival will be conducted in the future as specified in the protocol; a prespecified interim analysis of overall survival was conducted and is reported here. Results At the data-cutoff date for the primary analysis, the estimated rate of progression-free survival at month 20 was 65.2% (95% confidence interval [CI], 50.0 to 76.8) in the 177Lu-Dotatate group and 10.8% (95% CI, 3.5 to 23.0) in the control group. The response rate was 18% in the 177Lu-Dotatate group versus 3% in the control group (P<0.001). In the planned interim analysis of overall survival, 14 deaths occurred in the 177Lu-Dotatate group and 26 in the control group (P=0.004). Grade 3 or 4 neutropenia, thrombocytopenia, and lymphopenia occurred in 1%, 2%, and 9%, respectively, of patients in the 177Lu-Dotatate group as compared with no patients in the control group, with no evidence of renal toxic effects during the observed time frame. Conclusions Treatment with 177Lu-Dotatate resulted in markedly longer progression-free survival and a significantly higher response rate than high-dose octreotide LAR among patients with advanced midgut neuroendocrine tumors. Preliminary evidence of an overall survival benefit was seen in an interim analysis; confirmation will be required in the planned final analysis. Clinically significant myelosuppression occurred in less than 10% of patients in the 177Lu-Dotatate group. (Funded by Advanced Accelerator Applications; NETTER-1 ClinicalTrials.gov number, NCT01578239 ; EudraCT number 2011-005049-11
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