Research focusing on the reproducibility of MSU

Research focusing on the reproducibility of MSU measurement of CET is limited, with varying fair to excellent intra-class correlation coefficient (ICC) outcomes (Lee et al. 2011; Miller et al. 2002; Poltawski et al. 2012). Furthermore, intra-rater reliability and the smallest detectable change (SDC) were not determined (Lee et al. 2011), ordinal scales were used (Miller et al. 2002) or an ICC value for ordinal data instead of the recommended weighted κ value was applied (Poltawski et al. 2012, Fleiss and Cohen, 1973). Consequently, more insight into all reproducibility aspects of MSU thickness measurement of the CET, using objective quantitative measurements, is needed.
Earlier research on the reliability of MSU in other structures has indicated that p2y inhibitor MSU seems to be a rater-dependent technique (O\’Connor et al. 2005; Rutten et al. 2006). This variation seems to be specifically dependent on the level of experience and standardization of techniques (O\’Connor et al. 2005; Rutten et al. 2006). Therefore, the use of a standardized measurement protocol seems very important. However, all the studies performed on reproducibility of CET thickness measurements use various protocols. The protocols contain insufficient description of important standardization aspects that can negatively influence reproducibility. The protocols use subjective thickness measurements, without clear agreement on terminology and practice of the raters, lack measurable reference points for exact location of thickness measurements and/or fail to describe the positioning of the patients, including positioning of the elbow and accompanying joints (Lee et al. 2011; Miller et al. 2002; Poltawski et al. 2012). More insight into the reproducibility of CET thickness measurement, addressing these aspects, is needed.


Seventy-three healthy individuals participated in the study (44% females) with a mean (± SD) age of 35.7 (14.9) y and a mean (± SD) BMI of 23.9 (3.6) kg/m2. Sixty-four participants were right hand dominant. The descriptive data for longitudinal and transverse thickness of the CET, for both raters separately, are summarized in Table 1. There were no missing values, and all data were normally distributed.
Inter-rater reliability for both the longitudinal and transverse planes was fair to good (ICCs of 0.67 and 0.49, respectively). ICC values for intra-rater reliability for both raters as well as for longitudinal and transverse planes were excellent (ICCs = 0.85–0.92), with the exception of the ICC for rater 2 in the transverse plane, which was fair to good (ICC = 0.73). All ICC values were statistically significant with p-values < 0.001. The SDCs for both raters, as well as for longitudinal and transverse planes, ranged from 0.50 to 0.78 mm and comprised 9.8%–16.3% of the mean thickness. The ICC values for inter- and intra-rater reliability, the SDC values for intra-rater agreement and the intra-rater agreement with 95% limits of agreement are listed in Table 2.
Jaen-Diaz et al. (2010), Toprak et al. (2012) and Ustuner et al. (2013) determined reference values of 4.02–5.30 mm, 4.57 mm (SD ± 0.63) and 4.60 mm (SD ± 0.65), respectively, for CET thickness of the dominant arm in healthy people, which are comparable to our findings.
This is the first study that investigated all components of reproducibility of the MSU thickness measurements of CET in a large group of participants in the longitudinal and transverse planes. The results of the present study are comparable to the results of Krogh et al. (2013), who reported that intra-rater reliability varied between 0.76 and 0.81 and intra-reliability between 0.45 and 0.65. One study determined the inter-rater reliability of objective MSU thickness measurements of the CET in transverse plane only and found excellent inter-rater reliability for MSU measurements in healthy individuals and patients with a clinical diagnosis of LET (ICC = 0.86 and 0.75, respectively). The ICC value for the transverse thickness measurement from the present study was lower (ICC = 0.49). The thickness measurement in the longitudinal plane was better specified by means of bony landmarks, instead of the less exact location for measurement in transverse plane. This could explain the lower ICC value for inter-rater reliability for the transverse measurements compared with the results of Lee et al. (2011) and with the ICC values of the longitudinal measurements in the present study. Another explanation could be that the raters had less experience in measuring the CET thickness in the transverse plane because they use the longitudinal measurement more frequently in daily practice. Even though both measurements exhibited sufficient levels of reliability because of the excellent and fair outcomes, use of the longitudinal thickness measurement rather than the transverse measurement is recommended in daily practice.

The comorbidity condition in patients may

The comorbidity condition in patients may affect survival outcome and tolerance for toxicities. In order to clarify whether the comorbidity burden contributes as an independent prognostic factor for overall survival in mCRPC patients, we used the Charlson comorbidity index. In our study, CCI score was not significantly independent to overall survival and cancer-specific survival of patients receiving docetaxel-based chemotherapy, and the result was the same as the analysis by Goyal et al. A previous study still demonstrated CCI score had no association with overall survival in patients with locally advanced T3a prostate cancer. It is supposed that the difference in CCI scores between individuals is small in mCRPC patients, because it p2y inhibitor is at least six scores with distant metastases.
PSA level is generally considered to be related to tumor burden; therefore, PSA progression can present a negative impact to overall survival for mCRPC patients. As in Hussain et al\’s study, PSA progression was demonstrated as a significant prognostic factor of survival in patients of CRPC treated with chemotherapy. In our study, time to PSA progression was shown to be a predictor of overall survival and cancer-specific survival, which means longer time to PSA progression is associated with better survival outcome.


Conflicts of interest

Sources of funding

Since 2004, docetaxel chemotherapy has been reported to be effective and relatively safe in metastatic prostate cancer patients after failure with androgen deprivation therapy. Not only prolonging survival, docetaxel chemotherapy has also benefits of relief of bony pain and improved quality of life. Using a standard 3-weekly docetaxel regimen (75 mg/m), in the arm, 45% of patients had significant serum prostate-specific antigen (PSA) response (>50% reduction) with a median duration p2y inhibitor of 7.7 months; by contrast, patients using a 3-weekly mitoxantrone regimen, in the arm, had a 32% PSA response with a median duration of 7.8 months. Similarly, Kellokumpu-Lehtinen et al, reported in the that a 2-weekly docetaxel regimen (50 mg/m) had 49% PSA response while a standard 3-weekly docetaxel regimen had 42% PSA response. Moreover, docetaxel chemotherapy can also prolong the patients\’ overall survival in high-volume hormone-sensitive metastatic prostate cancer. Despite these promising data, there is a lack of ideal markers predicting for disease-specific survival or overall survival.
Currently, there is no clear consensus regarding the optimum duration or response predictors of chemotherapy for metastatic castrate-resistant prostate cancer (mCRPC) patients. Despite this, several small cohorts explored the prognostic significance of PSA-related parameters in mCRPC patients. Thomas et al reported in a cohort of 41 consecutive mCRPC patients treated with 3-weekly docetaxel chemotherapy that time to PSA nadir of <16 weeks is an independent unfavorable predictor for response duration and progression-free survival. These findings were consistent with those in the articles by professor Huang\'s group. Interestingly, Huang et al reported in a large cohort of 650 patients with advanced or metastatic prostate cancer treated with androgen deprivation therapy (ADT) that the time to PSA nadir is an independent prognostic predictor for disease progression. Although the real mechanism is unclear, the author thought it may reflect a complicated role of androgen–androgen receptor axis in prostate cancer. Indeed, recent studies also demonstrated that the development of lethal prostate cancer is also a dynamics process that follows the Darwinian evolutionary rule. Despite these conceptual progresses, it is important to know how to use these predictors in practice. Conflicts of interest
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Renal pedicle control is the most crucial step in both open and laparoscopic nephrectomy. A pedicle injury may result in massive blood loss and open conversion. Common laparoscopic devices used in securing the renal pedicle include the endovascular gastrointestinal anastomosis stapler (Endo-GIAs), traditional titanium clips, and nonabsorbable polymer ligating clips (Hem-o-lok; Weck Closure Systems, Research Triangle Park, NC, USA). Unfortunately these devices are not only expensive, but may also malfunction when used to secure the renal pedicle in laparoscopic nephrectomy.

As it can be seen in Fig the values

As it can be seen in Fig. 2, the values of the effective indentation modulus determined for the ULK-350nm and ULK-200nm films differ significantly, despite the same nominal porosity. The lack of a pronounced dependence of M on the applied static load indicates that the results are not influenced by the elastic properties of the substrate. The initial increase in the values of the effective indentation modulus and presence of the hysteresis in the load–unload curve is caused most probably by a small plastic deformation of the film\’s upper layer. Similar behavior was observed for porous organosilicate glasses with a porosity of 30% and a thickness of about 700nm [42]. The mean values of M calculated for the 350nm and 200nm thin films from all the measurement points acquired during the measurements were 6.3GPa±0.2GPa and 7.2GPa±0.2GPa, respectively.
The values of the effective indentation modulus determined for the ULK-46nm sample are presented in Figs. 3 and 4. In the first attempt, we used the rounded tip and relatively large values of the static load ranging from 270nN to 3350nN. The results obtained in this series of measurements are presented in Fig. 3a. The load–unload curve represents the mean values of M calculated as a function of the static load from 20 single point measurements. The error bars represent the corresponding values of the standard deviation. In p2y inhibitor to those presented in Fig. 2, the curve presented in Fig. 3a shows a very strong dependence on the applied static load. The mean values of M increase from 14GPa to 18GPa during load and decrease to about 15GPa during unload. The difference between the load and unload values of M has similar character to that visible in Fig. 2, namely it is smaller than the values of the standard deviation of the corresponding mean value and it decreases with the increasing value of the static load.
The strong increase in the values of the effective indentation modulus suggests a substrate influence. To minimize it, we had to reduce the size of the stress field expanding into the sample. This can be done by applying an AFM tip with a smaller tip radius and/or lower values of the static load. To ensure that radical change in the tip geometry will not influence the results obtained for the indentation modulus of the samples, we performed an additional test. The test sample was also a film of porous organosilicate glass but with a nominal porosity of 40% and thickness of 350nm. Due to the higher porosity content, the modulus of the test sample was lower than that of the ULK-350 sample. Thus, the test sample would deform more under the same load and the influence of the tip geometry would be even more pronounced. The measurement and data evaluation procedures were the same as for the thin-film samples. The mean value of the indentation modulus determined for the test sample with the blunt tip (cantilever #1) in the force range from 650nN to 4750nN was 3.6GPa±0.2GPa. Then we used a cantilever equipped with a standard sensor tip having radius in the range from 30nm to 50nm (cantilever#2). The force ranged from 160nN to 1500nN. The mean value of the indentation modulus obtained with the sharp tip was 3.9±0.1GPa. The result obtained for the indentation modulus with the sharp tip was in a good agreement with that obtained with the blunt tip. The small difference of 0.3GPa could be caused by differences in the actual and the assumed tip geometries, and the corresponding tip–sample contact conditions. We will use this difference in further analysis of the experimental data obtained for ULK-thin film samples sample. Namely, any difference in the data obtained with blunt and sharp tips smaller than 0.3GPa will be treated as negligible.
We repeated the measurements on sample ULK-46nm, but this time we used the cantilever #2 with a smaller tip radius. The applied static load ranged from 200nN to 1400nN. We performed 24 single point measurements. The curve representing the mean values of the M as a function of the applied static load is presented in Fig. 3b. The error bars represent the values of the corresponding standard deviation. As it can be seen in Fig. 3b, the mean values of M obtained for the ULK-46nm sample with standard tip still show dependence on the applied static load. The values of M increase from 8.6GPa to 10.2GPa during load and decrease to 9.2 during unload. The maximal value of M determined during this series of measurements is less than the minimal value of M determined for the same sample with help of the rounded tip.