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Quantitative DCE-MRI parameters including K trans (transfer constant min −1 ) can predict both response and outcome in breast cancer patients treated with neoadjuvant chemotherapy (NAC). Quantitative methods are time-consuming to calculate, requiring expensive software and interpretive expertise. For diagnostic purposes, signal intensity–time curves (SITCs) are used for tissue characterisation. In this study, we compare the ability of NAC-related changes in SITCs with K trans to predict response and outcomes. 73 women with primary breast cancer underwent DCE-MRI studies before and after two cycles of NAC. Patients received anthracycline and/or docetaxel-based chemotherapy. At completion of NAC, patients had local treatment with surgery & radiotherapy and further systemic treatments. SITCs for paired DCE-MRI studies were visually scored using a five-curve type classification schema encompassing wash-in and wash-out phases and correlated with K trans values and to the endpoints of pathological response, OS and DFS. 58 paired patients studies were evaluable. The median size by MRI measurement for 52 tumours was 38 mm (range 17–86 mm) at baseline and 26 mm (range 10–85 mm) after two cycles of NAC. Median baseline K trans (min −1 ) was 0.214 (range 0.085–0.469), and post-two cycles of NAC was 0.128 (range 0.013–0.603). SITC shapes were significantly related to K trans values both before ( χ 2  = 43.3, P  = 0.000) and after two cycles of NAC ( χ 2 = 60.5, P  = 0.000). Changes in curve shapes were significantly related to changes in K trans ( χ 2  = 53.5, P  = 0.000). Changes in curve shape were significantly correlated with clinical ( P  = 0.005) and pathological response ( P  = 0.005). Reductions in curve shape of ≥1 point were significant for overall improved survival using Kaplan–Meier analysis with a 5-year OS of 80.9 versus 68.6 % ( P  = 0.048). SITCs require no special software to generate and provide a useful method of assessing the effectiveness of NAC for primary breast cancer.

Background It has been reported that the protein binding rate of vancomycin (VCM) varies among individual patients. So, the authors investigated relevant factors that may affect free VCM concentration and target attainment of free area under the concentration-time curve (fAUC). Methods Thirty-nine patients were included. Multiple regression analysis was performed to determine the valuable factors in the free VCM concentration, and the target attainment of area under the concentration-time curve (AUC) 400–600 mg・h/L and fAUC200-300 mg・h/L was calculated. Results We found total protein was significant covariate for free VCM. Among 18 patients who were investigated for AUC and fAUC estimation, 9 patients (50.0%) and 12 patients (66.7%) reached AUC > 600 mg・h/L, and fAUC > 300 mg・h/L ( p  = 0.310), respectively. Conclusions Total protein is a significant predictor for free VCM estimation. And the fAUC-guided TDM for VCM TDM may contribute to more strict dosing than the AUC-guided TDM in hyper- or hypo-proteinemic population. Trial registration Retrospectively registered.

To assess the pharmacokinetic parameters of vancomycin in Chinese critically ill pediatric patients, children treated with vancomycin, hospitalized in the intensive care unit were included. Samples to determine peak and trough serum concentrations were obtained on the third day of treatment. Half‐life was significantly longer in neonates and showed a decreasing trend in infants and children. In patients aged ≥1 month, AUC24/MIC ≥400 was achieved in 31.8% at the dose of 40 mg/kg/d, and in 48.7% at the dose of 60 mg/kg/d with an assumed MIC of 1 mg/L. Augmented renal clearance (ARC) was present in 27.3% of children, which was associated with higher vancomycin clearance and lower AUC values. A good correlation was observed between trough concentration and AUC24, and the trough concentration that correlated with AUC24 of 400 were varied according to the dosage regimens, 8.42 mg/L for 6‐hintervals, and 6.63 mg/L for 8‐h intervals. To conclude, vancomycin trough concentration that related to the AUC24 of 400 was much lower in critically ill children than that in adults. The dosage of 60 mg/kg/day did not enough for producing AUC24 in the range of 400–600 mg h/L in critically ill children, especially in those with ARC. A good correlation was observed between trough concentration and AUC24. The trough concentration that correlated with AUC24 of 400 were varied according to the dosage regimens, 8.42 mg/L for 6‐h intervals, and 6.63 mg/L for 8‐h intervals.

The therapeutic drug monitoring (TDM) of vancomycin (VCM) in critically ill patients often results in the estimated area being under the concentration–time curve (AUC) values that deviate from individual observations. In this study, we investigated the factors influencing the achievement of the target AUC of VCM at steady-state in critically ill patients. We retrospectively collected data from patients treated with VCM in an intensive care unit (ICU). Multivariate analysis was used to adjust for significant factors with p < 0.05 and identify new factors affecting the achievement of the target AUC at steady-state for VCM. Among the 113 patients included in this study, 72 (64%) were in the 1-point group (trough only), whereas 41 (36%) were in the 2-point group (trough/peak). The percentage of patients achieving the target AUC at the follow-up TDM evaluation was significantly higher in the two-point group. Multivariate analysis showed that being in the 2-point group and those with a 20% or more increase (or decrease) in creatinine clearance (CCr) were both significantly associated with the success rate of achieving the target AUC at the follow-up TDM. Novel findings revealed that in patients admitted to the ICU, changes in renal function were a predictor of AUC deviation, with a 20% or more increase (or decrease) in CCr being an indicator. We believe the indicators obtained in this study are simple and can be applied clinically in many facilities. If changes in renal function are anticipated, we recommend an AUC evaluation of VCM with a two-point blood collection, close monitoring of renal function, and dose adjustment based on reanalyzing the serum concentrations of VCM.

We present the application of a simple probabilistic methodology to determine the reliability of a structural element exposed to fire when designed following Eurocode 1-1-2 (EC1). Eurocodes are being used extensively within the European Union in the design of many buildings and structures. Here, the methodology is applied to a simply-supported, reinforced concrete slab 180 mm thick, with a standard load bearing fire resistance of 90 min. The slab is subjected to a fire in an office compartment of 420 m2 floor area and 4 m height. Temperature time curves are produced using the EC1 parametric fire curve, which assumes uniform temperature and a uniform burning condition for the fire. Heat transfer calculations identify the plausible worst case scenarios in terms of maximum rebar temperature. We found that a ventilation-controlled fire with opening factor 0.02 m1/2 results in a maximum rebar temperature of 448°C after 102 min of fire exposure. Sensitivity analyses to the main parameters in the EC1 fire curves and in the EC1 heat transfer calculations are performed using a one-at-a-time (OAT) method. The failure probability is then calculated for a series of input parameters using the Monte Carlo method. The results show that this slab has a 0.3% probability of failure when the compartment is designed with all layers of safety in place (detection and sprinkler systems, safe access route, and fire fighting devices are available). Unavailability of sprinkler systems results in a 1% probability of failure. When both sprinkler system and detection are not available in the building, the probability of failure is 8%. This novel study conducts for the first time a probabilistic calculation using the EC1 parametric curve, helping engineers to identify the most critical design fires and the probabilistic resistance assumed in EC1.

Thermal tolerance is a critical determinant of ectotherm distribution, which is likely to be influenced by future climate change. To predict such distributional changes, simple and comparable measures of heat tolerance are needed and these measures should ideally correlate with the characteristics of the species current thermal environments. A recent model (thermal tolerance landscapes—TTLs) uses the exponential relation between temperature and knockdown time to describe the thermal tolerance of ectotherms across time/temperature scales. Here, we established TTLs for 11 Drosophila species representing different thermal ecotypes by measuring knockdown time at 9–17 stressful temperatures (0.5°C intervals). These temperatures caused knockdown times ranging from <10 min to >12 hrs and all species displayed the expected exponential relation between temperature and knockdown time (average R2 = 0.98). Previous studies using TTLs have reported a trade‐off between tolerance to acute and chronic heat stress in ectotherms. The present study did not find evidence to support this trade‐off in drosophilids. Instead, we show how this “trade‐off” can arise as an analytical artefact caused by insufficient data collection and excessive data extrapolation. Dynamic assays represent an alternative method to describe heat tolerance of ectotherms, where animals are exposed to gradually increasing temperatures until knockdown. The comparability of static and dynamic assays has previously been questioned, but here we show that static and dynamic assays give comparable information on heat tolerance. Using the constants derived from static TTLs, we mathematically model the expected dynamic knockdown temperature and subsequently confirm this model by comparison to empirically obtained knockdown temperatures from all 11 species. Characterisation of heat tolerance in laboratory settings is an important tool in thermal biology, but more so if the measures correlate with the environmental gradients that characterise the fundamental niche of species. Here, we show that both static and dynamic assays were characterised by strong correlations to precipitation of the driest month and maximum temperature of the warmest month combined (R2 = 0.68–0.71). This demonstrates that both assay types offer simple measures of heat tolerance that are ecologically relevant for the tested drosophilids. A plain language summary is available for this article. Plain Language Summary

The study was aimed to evaluate the right ventricular function in pneumoconiosis patients by real-time three-dimensional echocardiography. A total of 80 individuals including 44 consecutive pneumoconiosis patients and 36 age- and gender-matched healthy volunteers as controls were prospectively recruited for the study. All the patients underwent two- and three-dimensional echocardiography. Measurements of the right ventricle included tricuspid regurgitation pressure (TRPG), anterior and posterior wall thickness and range of motion (TH1, TH2, M1, M2), right end-diastolic volume and end-systolic volume. The right ventricular ejection fraction (RVEF) was also calculated. The RVEF of healthy volunteers ranged from 50 to 78 %, whereas that of the pneumoconiosis patients varied from 29 to 73 %. An increase in TRPG caused a significant ( p  = 0.006) decrease in RVEF (by 77.3 %), suggesting the two variables were negatively correlated ( r  = −0.643, p  < 0.01). In comparison with normal, the volume–time curves of the pneumoconiosis patients showed a lower trough. Use of real-time three-dimensional echocardiography provides with added clinical information needed to evaluate right ventricular function in pneumoconiosis patients.

Purpose: In recent years, cardiac magnetic resonance (CMR) has been used to assess LV diastolic function. In this systematic review, studies were identified where CMR parameters had been evaluated in healthy and/or patient groups with proven diastolic dysfunction or known to develop heart failure with preserved ejection fraction. We aimed at describing the parameters most often used, thresholds where possible, and correlation to echocardiographic and invasive measurements. Methods and results: A systematic literature review was performed using the databases of PubMed, Embase, and Cochrane. In total, 3808 articles were screened, and 102 studies were included. Four main CMR techniques were identified: tagging; time/volume curves; mitral inflow quantification with velocity-encoded phase-contrast sequences; and feature tracking. Techniques were described and estimates were presented in tables. From published studies, peak change of torsion shear angle versus volume changes in early diastole (−dφ′/dV′) (from tagging analysis), early peak filling rate indexed to LV end-diastolic volume <2.1 s−1 (from LV time-volume curve analysis), enlarged LA maximal volume >52 mL/m2, lowered LA total (<40%), and lowered LA passive emptying fractions (<16%) seem to be reliable measures of LV diastolic dysfunction. Feature tracking, especially of the atrium, shows promise but is still a novel technique. Conclusion: CMR techniques of LV untwisting and early filling and LA measures of poor emptying are promising for the diagnosis of LV filling impairment, but further research in long-term follow-up studies is needed to assess the ability for the parameters to predict patient related outcomes.

Background Reflux and aspiration in people are associated with respiratory disease, whereas approximately 50% of healthy adults microaspirate without apparent consequence. In dogs, analogous information is lacking. Hypothesis Healthy dogs commonly have gastroesophageal reflux and a proportion of these dogs will have laryngopharyngeal reflux with silent aspiration. Animals Twelve healthy, client‐owned dogs. Methods Prospective study: Dogs were free‐fed a meal containing (111 MBq) colloidal 99m‐technetium phytate. Dynamic‐scans were performed 5 and 30 minutes postingestion. Time‐activity curves, reflux margination, volume, frequency, and duration were evaluated over 7 regions of interest in dorsal ± left‐lateral recumbency. Static scans (dorsal recumbency) were performed 2 and 18 hours postfeeding to detect aspiration. Reflux and aspiration were defined as counts ≥200% background activity ± decreased gastric counts. Between‐group comparisons were performed by Wilcoxon rank‐sum test or one‐way ANOVA on ranks with significance of P < .05. Results In this study, reflux of variable magnitude was detected in 12/12 dogs. No significant differences in outcome parameters were detected with recumbency (P > .05). Margination to the pharynx and proximal, middle, and distal esophagus was identified in 5/12, 2/12, 3/12, and 2/12 dogs, respectively. Median (IQR) reflux frequency and duration were 2 events/5 minutes (1‐3.3 events/5 minutes) and 6 seconds (4‐9 seconds) respectively. No dog had detectable aspiration. Conclusions and Clinical Importance Nuclear scintigraphy can document reflux in dogs. Reflux, but not aspiration, is common in healthy dogs and must be considered when interpreting results in clinically affected dogs.

Eight male collegiate weightlifters (age: 21.2 +/- 0.9 years; height: 177.6 +/- 2.3 cm; and body mass: 85.1 +/- 3.3 kg) participated in this study to compare isometric to dynamic force-time dependent variables. Subjects performed the isometric and dynamic mid-thigh clean pulls at 30-120% of their one repetition maximum (1RM) power clean (118.4 +/- 5.5 kg) on a 61 x 121.9-cm AMTI forceplate. Variables such as peak force (PF) and peak rate of force development (PRFD) were calculated and were compared between isometric and dynamic conditions. The relationships between force-time dependent variables and vertical jump performances also were examined. The data indicate that the isometric PF had no significant correlations with the dynamic PF against light loads. On the one hand, there was a general trend toward stronger relationships between the isometric and dynamic PF as the external load increased for dynamic muscle actions. On the other hand, the isometric and dynamic PRFD had no significant correlations regardless of the external load used for dynamic testing. In addition, the isometric PF and dynamic PRFD were shown to be strongly correlated with vertical jump performances, whereas the isometric PRFD and dynamic PF had no significant correlations with vertical jump performances. In conclusion, it appears that the isometric and dynamic measures of force-time curve characteristics represent relatively specific qualities, especially when dynamic testing involves small external loads. Additionally, the results suggest that athletes who possess greater isometric maximum strength and dynamic explosive strength tend to be able to jump higher.Eight male collegiate weightlifters (age: 21.2 +/- 0.9 years; height: 177.6 +/- 2.3 cm; and body mass: 85.1 +/- 3.3 kg) participated in this study to compare isometric to dynamic force-time dependent variables. Subjects performed the isometric and dynamic mid-thigh clean pulls at 30-120% of their one repetition maximum (1RM) power clean (118.4 +/- 5.5 kg) on a 61 x 121.9-cm AMTI forceplate. Variables such as peak force (PF) and peak rate of force development (PRFD) were calculated and were compared between isometric and dynamic conditions. The relationships between force-time dependent variables and vertical jump performances also were examined. The data indicate that the isometric PF had no significant correlations with the dynamic PF against light loads. On the one hand, there was a general trend toward stronger relationships between the isometric and dynamic PF as the external load increased for dynamic muscle actions. On the other hand, the isometric and dynamic PRFD had no significant correlations regardless of the external load used for dynamic testing. In addition, the isometric PF and dynamic PRFD were shown to be strongly correlated with vertical jump performances, whereas the isometric PRFD and dynamic PF had no significant correlations with vertical jump performances. In conclusion, it appears that the isometric and dynamic measures of force-time curve characteristics represent relatively specific qualities, especially when dynamic testing involves small external loads. Additionally, the results suggest that athletes who possess greater isometric maximum strength and dynamic explosive strength tend to be able to jump higher.