Modeling of liquid-liquid hollow fiber supported membrane equilibrium including the non-ideality of the aqueous and organic phases in the recovery systems of radionuclides in sulphate-halide/aliquat-336 in O-xylene.

Study of modeling of L/LHFSLM equilibrium based on the Non-ideality of the Aqueous and Organic Phases in the Recovery of 152+154Eu in H2SO4-Halides/Aliquat-336 in 20% kerosene as feeding phase at pH 3.78-4.55, by the ratio 89.7%,while separation of 90Sr and 134Cs there was a problem between them by using hollow HFSLM only, the reason for that the organic solvents affect the rate of reaction in the Diamino-1,2-cyclohexane/tetraacetic acid (DCTA) as stripping phase concentration from 0.15 to 0.55 mol/L. The system has been developed; this led to the extraction of elements in the same time. The Matlab software program was introduced to obtain some mathematical parameters like, standard deviation (SD), equilibrium constant Kex and standard deviation coefficient (SDC).

The effect of Mozart music on patient satisfaction during caesarean delivery: a randomised controlled trial.

BACKGROUND: Music is a low-cost intervention that can improve patient satisfaction. METHODS: This was a prospective, randomised, controlled trial conducted at an urban tertiary care academic medical centre in the United States. Nulliparous women 18-50 years old with a healthy singleton pregnancy at ≥ 37 weeks gestational age undergoing elective caesarean delivery under neuraxial anaesthesia were randomised to the music group (Mozart sonatas) or control group (no music). Mozart sonatas were broadcast to the music group immediately prior to patient entry and maintained throughout the procedure. The primary outcome was patient satisfaction using the Maternal Satisfaction Scale for Caesarean Section (MSSCS). Secondary outcomes were changes in anxiety pre- and post-operatively and post-operative mean arterial pressure (MAP). Student's t-test, the Wilcoxon rank sum test, and the c2 test were used where appropriate for statistical analyses. RESULTS: 27 parturients were evaluated for participation between 2018 and 2019, and 22 enrolled. The final study subject number was 20 due to two withdrawals. There were no clinically meaningful differences in baseline demographics, vital signs, and anxiety. The mean (SD) total patient satisfaction for music vs. control was 116 (16) vs. 120 (22), mean difference 4 (95% CI: -14.0 to 22.0), P = 0.645. The mean (SD) change in anxiety with music vs. control was 2.7 (2.7) vs. 2.5 (2.6), mean difference -0.4 (95% CI: -4.0 to 3.2), P = 0.827. The median (IQR) post-operative MAP with music vs. control was 77.7 (73.7-85.3) vs. 77.3 (72.0-87.3), P = 0.678. CONCLUSIONS: The use of Mozart sonatas did not result in improvements in patient satis-faction, anxiety or MAP in parturients undergoing elective caesarean delivery.

Introduction to the Use of Linear and Nonlinear Regression Analysis in Quantitative Biological Assays.

Biological assays are essential tools in biomedical and pharmaceutical research. In simplest terms, such an assay is an analytical method used to measure or predict a response in a biological system in the presence of a given stimulus (e.g., drug). The inherent complexity involved in evaluating a biological system requires the use of rigorous and appropriate tools for data analysis. Linear and nonlinear regression models represent critically important statistical analyses used to define the relationships between variables of interest in biological systems. Recent challenges relating to the reproducibility of published data suggest the absence of standardized and routine use of statistics to support experimental results across a wide range of scientific disciplines. The current situation warrants an introductory review of basic regression concepts using current, practical examples, along with references to in-depth resources. The goal is to provide the necessary information to help standardize the analysis of biological assays in academic research and drug discovery and development, elevating their utility and increasing data transparency and reproducibility. © 2023 The Authors. Current Protocols published by Wiley Periodicals LLC.

Quantitative evaluation of density variability in the lesion-lung boundary zone to differentiate pulmonary subsolid nodules.

Background: Transition of the CT values from nodule to peripheral normal lung is related to pathological changes and may be a potential indicator for differential diagnosis. This study investigated the significance of the standard deviation (SD) values in the lesion-lung boundary zone when differentiating between benign and neoplastic subsolid nodules (SSNs). Methods: From January 2012 to July 2021, a total of 229 neoplastic and 84 benign SSNs confirmed by pathological examination were retrospectively and nonconsecutively enrolled in this study. The diagnostic study was not registered with a clinical trial platform, and the study protocol was not published. Computed tomography (CT) values of the ground-glass component (CT1), adjacent normal lung tissue (CT2), and lesion-lung boundary zone (CT3) were measured consecutively. The SD of CT3 was recorded to assess density variability. The CT1, CT2, CT3, and SD values were compared between benign and neoplastic SSNs. Results: No significant differences in CT1 and CT2 were observed between benign and neoplastic SSNs (each P value >0.05). CT3 (-736.1±51.0 vs. -792.6±73.9; P<0.001) and its SD (135.6±29.6 vs. 83.6±20.6; P<0.001) in neoplastic SSNs were significantly higher than those in benign SSNs. Moreover, the SD increased with the invasiveness degree of neoplastic SSNs (r=0.657; P<0.001). The receiver operating characteristic (ROC) curve revealed that the area under the curve was 0.927 (95% CI: 0.896-0.959) when using the SD (cutoff value =106.98) as a factor to distinguish SSNs, which increased to 0.966 (95% CI: 0.934-0.985) when including nodules with a CT1 of ≥-715 Hounsfield units (HU) only (cutoff of SD 109.9, sensitivity 0.930, and specificity 0.914). Conclusions: The SD as an objective index is valuable for differentiating SSNs, especially for those with a CT1 of ≥-715 HU, which have a higher possibility of neoplasm if the SD is >109.9.

Timing of Spheno-Occipital Synchondrosis Closure in Cleft Lip and Palate Patients in Iranian Population.

This study aimed to evaluate the chronological age range associated with each stage of spheno-occipital synchondrosis (SOS) fusion in patients with cleft lip and palate compared to the noncleft group, using cone-beam computed tomography (CBCT) images.In this study, the degree of SOS fusion was assessed using a 4-stage scoring system on CBCT images of 190 individuals (92 patients with cleft lip and palate, 98 noncleft individuals). A χ2 test was performed to assess the correlation between age and fusion stage. The independent sample t tests were used to evaluate the differences in the mean values of the samples of each group and each sex, as well as the mean value of each stage (P < .05).The results showed that there was no significant difference in the timing of the SOS fusion stages between the patients with cleft palate and the noncleft group. Although the fusion process of SOS begins about one year earlier in females, the complete ossification occurs at the mean age of 18.5 for both sexes in the experimental group and the mean age of 19.0 in the noncleft group.The present study found no differences in the fusion stages of the spheno-occipital synchondrosis between patients with cleft lip and palate and healthy individuals.

3D bioprinting of in situ vascularized tissue engineered bone for repairing large segmental bone defects.

Large bone defects remain an unsolved clinical challenge because of the lack of effective vascularization in newly formed bone tissue. 3D bioprinting is a fabrication technology with the potential to create vascularized bone grafts with biological activity for repairing bone defects. In this study, vascular endothelial cells laden with thermosensitive bio-ink were bioprinted in situ on the inner surfaces of interconnected tubular channels of bone mesenchymal stem cell-laden 3D-bioprinted scaffolds. Endothelial cells exhibited a more uniform distribution and greater seeding efficiency throughout the channels. In vitro, the in situ bioprinted endothelial cells can form a vascular network through proliferation and migration. The in situ vascularized tissue-engineered bone also resulted in a coupling effect between angiogenesis and osteogenesis. Moreover, RNA sequencing analysis revealed that the expression of genes related to osteogenesis and angiogenesis is upregulated in biological processes. The in vivo 3D-bioprinted in situ vascularized scaffolds exhibited excellent performance in promoting new bone formation in rat calvarial critical-sized defect models. Consequently, in situ vascularized tissue-engineered bones constructed using 3D bioprinting technology have a potential of being used as bone grafts for repairing large bone defects, with a possible clinical application in the future.

Increased Intra-Individual Variability as a Marker of Executive Dysfunction in Generalized Anxiety Disorder.

Recent studies suggest that individual difference in intra-individual variability (IIV) of reaction times is an important indicator of attentional executive control. However, there are few existing studies on the executive control of high trait-anxious individuals assessed by using reaction time variability. This study assessed whether executive functions are impaired among clinical and non-clinical trait-anxious individuals indicated by IIV. The cross-reliability and discriminative power of three IIV parameters (raw intra-individual standard deviation, SD; reaction time coefficient of variation, RTCV; and mean absolute deviation, MAD) were compared. Twenty-five non-clinical individuals with low trait anxiety (LTA), 31 non-clinical individuals with high trait anxiety (HTA), and 19 clinical patients diagnosed with generalized anxiety disorder (GAD) finished self-reported measures, an emotional spatial-cuing task, and a non-emotional arrow flanker task. In the emotional task, GAD patients had significantly slower response speed, lower accuracy, and greater IIV parameters than the LTA and HTA groups. In the non-emotional task, the GAD group exhibited poorer processing efficiency, greater SD and RTCV, and intact performance effectiveness. RTCV is suggested to be a better marker of executive dysfunction than SD and MAD due to its good discriminative power and reliability as well as less affected by reaction times.

Preventive strategy of flatfoot deformity using fully automated procedure.

A non-invasive, no radiation, out-of-hospital automated system is proposed to identify low arch integrated in the design and manufacturing of personalized orthoses using parametric modelling. The aim of the design process is to integrate assistive technology with assessment and prevent low arch progressing to a more serious case - flatfoot. In the automated procedure, we developed an assessment method including reliable thresholds of foot type classification and test protocol to reduce interferences due to preceding activities, an automation to translate scanned data into parametric design for orthotic customization, finite element model evaluating effectiveness of the personalized design, and a personalized comparative test to evaluate the long-term improvement of foot arch shape. Our low arch threshold established by subject-specific 3D models reduced the misclassification rate from 55%, as previously reported to 6.9%. Individuals who engaged in sedentary activity (i.e. sitting) had the greater change in arch height compared to active activity (i.e. standing and walking), which is more likely to affect the obtained measure. Therefore, a test protocol now states that participants are not allowed to sit over 100 min prior the measurement to reduce such interference. We have proposed and tested an automated algorithm to translate scanned data including seven foot's parameters into customised parametric design of the insert. The method decreases the required time of orthotic computer-aided design from over 3 h to less than 2 min. A finite element analysis procedure was additionally developed to assess the performance of geometries and material of designed orthotic based on the distribution of plantar pressure and internal stress. The personalized comparative assessment based on midfoot contact area was carried out periodically for follow-up and the orthotic could be re-designed if necessary. The proposed automated procedure develops a pre-screening system to distinguish low arch and provide preventatives before it becomes symptomatic. Furthermore, non-symptom flatfoot can be detected at early stages and referred to medics for further diagnosis or treatment.

A real-world single-centre analysis of alemtuzumab and cladribine for multiple sclerosis.

BACKGROUND: Highly active MS may warrant higher efficacy treatments for disease control. However, these often confer more risk and have not been compared in head-to-head clinical trials, making relative efficacy and safety difficult to interpret. Alemtuzumab and cladribine are two high-efficacy treatments given as discrete courses separated by one year, followed by a durable response that potentially does not require ongoing treatment. Before the approval of oral cladribine, our centre had been treating patients with a bioequivalent intravenous (IV) regimen since 2010. The objective of this study is to report the safety and efficacy data of alemtuzumab and cladribine in a real-world, single centre setting. METHODS: We retrospectively reviewed all patients treated with alemtuzumab or cladribine at the Ottawa Hospital MS Clinic with 2 or more years of follow-up. Information on baseline demographic variables, previous treatment, and prior disease activity was collected. Outcomes investigated were "no evidence of disease activity" (NEDA) and its constituents: new clinical relapse, new MRI activity, and Expanded Disability Status Scale (EDSS) progression; as well as any adverse events or treatment discontinuation. We performed univariate and multiple logistic regression to determine differences in 2-year NEDA and time-to-event analyses with Cox regression models to determine factors associated with each outcome through the study period. RESULTS: Forty-six patients were treated with alemtuzumab and 65 with cladribine of whom 51 (78%) received the intravenous regimen, followed for a total of 420.1 person-years. The cladribine group was older (p=.0002), with higher baseline EDSS (p=.0015), and more likely secondary progressive (p<.0001). Alemtuzumab had a higher rate of 2-year NEDA than cladribine (OR 4.78, 95%CI: 1.57-14.50, p=.006), but beyond 2 years the difference was not statistically significant (HR 0.50, 95%CI: 0.25-1. 30, p=.061). More prior treatments were associated with lower likelihood of retaining NEDA (HR 1.26, 95%CI: 1.03-1.54, p=.027). Alemtuzumab had more infusion reactions (80% vs. 17%, p<.0001), shingles (22% vs. 2%, p=.005), and secondary autoimmunity (52% vs. 3%, p<.0001) than cladribine, but there was no difference in grade 3 or higher adverse events (21.7% vs. 18.5%, p=1.0). CONCLUSION: In our cohort alemtuzumab and cladribine achieved similar rates of NEDA in long-term follow-up, with overall less adverse events with cladribine. Patient registries would allow more robust comparisons, detection of adverse events, and assessment of a durable response.

Shared breastfeeding & other early multiple sclerosis risk factors: A case-control study.

BACKGROUND: Multiple sclerosis (MS) is a chronic inflammatory autoimmune disease. Etiology is thought to be multifactorial with genetic and environmental factors interplay. Our objective in this study is to evaluate culture specific and other early life risk factors for MS. We examined the association between MS and breastfeeding including shared breastfeeding, parental consanguinity, being born abroad or living abroad during childhood, prematurity, vaccination, tonsillectomy, rank among siblings, number of siblings, number of household members (HHM) at birth, and age first time joining school. METHODS: This is an age and sex matched case-control study that was conducted in Riyadh, Kingdom of Saudi Arabia (KSA). We enrolled 300 cases and 601 controls. A structured questionnaire about demographics, consanguinity and potential environmental factors was answered by participants. Data was analyzed using logistic regression adjusting for covariates occurring later in life such as waterpipe smoking and performing Hajj. RESULTS: About two thirds of the cases and the controls were females. Mean age was 34.8 (9.2) for the cases and 33.6 (10.6) for the controls. We found that shared breastfeeding (OR=0.58; 95% CI, 0.35-0.96, p = 0.033), and older age first joining school (OR=0.83; 95% CI, 0.73-0.94, p = 0.005) were associated with decrease risk of MS. While longer duration of breastfeeding by biological mother (OR=1.03; 95% CI, 1.01-1.04, p = 0.001), rank among siblings of ≥6 (OR=1.69; 95% CI, 1.11-2.56, p = 0.014), and larger number of HHM at birth (OR=2.32; 95% CI, 1.64-3.28, p = 0.001) were associated with increased risk. Patients with MS were less likely to receive formula with breastfeeding than controls (OR=0.72; 95% CI, 0.51-0.99, p = 0.046). No association was found with breastfeeding by biological mother, number of siblings, prematurity, being born abroad or living abroad during childhood, vaccination, consanguinity, or tonsillectomy. CONCLUSION: The findings of this case-control study add to the accumulating evidence that early life factors could modify the risk of developing MS. Among these, novel associations with shared breastfeeding and number of HHM at birth are suggested. Future studies are needed to verify the observed results.

The efficacy and safety of intravenous tranexamic acid in hip fracture surgery: A systematic review and meta-analysis.

OBJECTIVE: The present meta-analysis was conducted to compare the efficacy and safety of intravenous application of tranexamic acid (TXA) with placebo in patients with hip fracture undergoing hip surgeries. METHODS: PubMed, EMBASE and Cochrane Library were searched from inception until March 2018. A combined searching strategy of subject words and random words was adopted. Only randomized clinical trials were included. The comparisons regarding transfusion rate, total blood loss, intraoperative blood loss, postoperative blood loss, postoperative haemoglobin and postoperative thromboembolic complications were conducted. The meta-analysis was performed using Review Manager 5.3, and the bias evaluation was based on the Cochrane Handbook 5.1.0. RESULTS: Ten randomized controlled trials published from 2007 to 2018 were included in the meta-analysis. The results showed that there were significant differences in the two groups concerning transfusion rate of allogeneic blood [risk ratio (RR) = 0.66, 95% confidence interval (CI): 0.56 to 0.78, P = 0.003], total blood loss [mean difference (MD) = -273.00, 95% CI: -353.15 to -192.84, P < 0.00001], intraoperative blood loss (MD = -76.63, 95% CI: -139.55 to -13.71, P = 0.02), postoperative blood loss (MD = -125.29, 95% CI: -221.96 to -28.62, P = 0.01) and postoperative haemoglobin (MD = 0.80, 95% CI: 0.38 to 1.22, P = 0.0002). Nonsignificant differences were found in the incidence of thromboembolic events (RR = 1.38, 95% CI: 0.74 to 2.55, P = 0.31). CONCLUSIONS: This meta-analysis of the available evidence implies that the intravenous route of TXA shows an ability to reduce transfusion requirements and total blood loss, not increasing the incidence of thromboembolic events in patients undergoing hip surgeries. THE TRANSLATIONAL POTENTIAL OF THIS ARTICLE: The result of this meta-analysis shows that the utilization of intravenous TXA in patients with hip fracture undergoing hip surgeries possesses great potential in reducing blood loss and allogeneic blood transfusion safely.

How standard deviation contributes to the validity of a LDF signal: a cohort study of 8 years of dental trauma.

The aim of this cohort study was to document the potential of laser Doppler flowmetry (LDF) for diagnosing tooth vitality in traumatized teeth in a population of 88 referred patients with dental trauma over a period of 8 years (2011-2018). The main reason to refer was tooth discoloration (26%), and the main trauma cause was a traffic injury (35%). Taking into account that referral for LDF is best given within the week after trauma, 66% of referrals were overdue. In 73% of cases, root canal treatment could be avoided, and in 65%, the presence of a fixed orthodontic retainer showed beneficial for pulp recovery. Data of 394 teeth were collected and submitted to multilevel modelling statistics. As a general conclusion, both LDF perfusion and concentration values proved to be highly reliable in the appreciation of tooth vitality. The difference of variability of standard deviation and range of LDF measurements involving intra-subject control teeth showed statistically significant in discriminating between vital and non-vital pulps. In non-vital teeth, the diagnostic combination of LDF, sensibility tests and peri-apical X-ray is advised.

The correlation between baseline score and post-intervention score, and its implications for statistical analysis.

BACKGROUND: When using a continuous outcome measure in a randomised controlled trial (RCT), the baseline score should be measured in addition to the post-intervention score, and it should be analysed using the appropriate statistical analysis. METHODS: We derive the correlation between the change score and baseline score and show that there is always a correlation (usually negative) between the change score and baseline score. We discuss the following correlations and provide the mathematical derivations in the Appendix: Correlation between change score and baseline score Correlation between change score and post score Correlation between change score and average score. The setting here is a parallel, two-arm RCT, but the method discussed in this paper is applicable for any studies or trials that have a continuous outcome measure; it is not restricted to RCTs. RESULTS: We show that using the change score as the outcome measure does not address the problem of regression to the mean, nor does it take account of the baseline imbalance. Whether the outcome is change score or post score, one should always adjust for baseline using analysis of covariance (ANCOVA); otherwise, the estimated treat effect may be biased. We show that these correlations also apply when comparing two measurement methods using Bland-Altman plots. CONCLUSIONS: The correlation between baseline and post-intervention scores can be derived using the variance sum law. We can then use the derived correlation to calculate the required sample size in the design stage. Baseline imbalance may occur in RCTs, and ANCOVA should be used to adjust for baseline in the analysis stage.

Serum copper levels are associated with bone mineral density and total fracture.

BACKGROUND: Both copper deficiency and overexposure have been associated with adverse health effects. Evidence linking copper to bone mineral density (BMD) and total fracture, however, is limited. METHODS: This nationally representative cross-sectional study enrolled participants from the National Health and Nutrition Examination Survey (2011-2014) in the United States. Using unadjusted and multivariate adjusted logistic regression analyses and a two-piecewise linear regression model with a smoothing function, we evaluated the associations between serum copper levels, bone mineral density and total fracture in 722 participants. RESULTS: The study sample (n = 722, mean age: 56.47 ± 11.55 y) represented a population of which 47.2% were men; 43.91% were non-Hispanic white, 18.84% non-Hispanic black and 13.71% Mexican American; 25.9% had total fracture. In the multivariate logistic regression analysis, individuals in the lowest category (<98.5 µg/dL) of serum copper concentration had 0.049 g/cm2 lower total femur BMD and 0.045 g/cm2 lower femoral neck BMD than those in the second concentration category (98.5-114 µg/dL). Individuals in the highest category (≥134 µg/dL) of serum copper concentration had an approximately 4-fold increase in the risk of total fracture than those in the second concentration category. There were no significant associations between per 10 µg/dL increases in serum copper levels and total fracture in multivariate logistic regression analysis after multivariate adjustment (all p > 0.05). However, a differential association between serum copper levels and total fractures between men and women was observed (odds ratio = 1.81, 95% confidence interval 1.08-3.03, p = 0.026 for men and odds ratio = 1.07, 95% confidence interval 0.86-1.32, p = 0.552 for women). CONCLUSION: Moderate serum copper levels are critically important for bone health. Lower serum copper levels are significantly associated with decreased BMD in the total femur and femoral neck. Higher serum copper levels are significantly associated with increased total fracture, especially in men. THE TRANSLATIONAL POTENTIAL OF THIS ARTICLE: The impact of serum copper concentrations on bone mineral density and total fracture can provide insights into clinical application of copper-containing supplements and biomaterials.

The preclinical evaluation of the dual mTORC1/2 inhibitor INK-128 as a potential anti-colorectal cancer agent.

The colorectal cancer is the leading contributor of cancer-related mortality. Mammalian target of rapamycin (mTOR), existing in 2 complexes (mTORC1/2), is frequently dysregulated and constitutively activated in colorectal cancers. It represents an important drug target. Here we found that INK-128, the novel ATP-competitive kinase inhibitor of mTOR, blocked both mTORC1 and mTORC2 activation in colorectal cancer cells (both primary and transformed cells). The immunoprecipitation results showed that the assembly of mTORC1 (mTOR-Raptor association) and mTORC2 (mTOR-Rictor-Sin1 association) was also disrupted by INK-128. INK-128 inhibited colorectal cancer cell growth and survival, and induced both apoptotic and non-apoptotic cancer cell death. Further, INK-128 showed no effect on Erk/MAPK activation, while MEK/Erk inhibition by MEK-162 enhanced INK-128-induced cytotoxicity in colorectal cancer cells. Meanwhile, INK-128 downregulated Fascin1 (FSCN1)/E-Cadherin expressions and inhibited HT-29 cell in vitro migration. In vivo, daily INK-128 oral administration inhibited HT-29 xenograft growth in mice, which was further enhanced by MEK-162 administration. Finally, we found that INK-128 sensitized 5-fluorouracil-(5-FU)-mediated anti-HT-29 activity in vivo and in vitro. Thus, our preclinical studies strongly suggest that INK-128 might be investigated for colorectal cancer treatment in clinical trials.

Investigation of Characteristics of Japanese Clinical Trials in Terms of Data Variability.

BACKGROUND: Because Asian countries have become involved in multiregional clinical trials, it is increasingly important to understand the characteristics of each country in terms of clinical trials to seek an appropriate strategy for worldwide drug development. Since variability of data is one of the important factors in clinical trials, variability of Japanese data, such as shown in coefficient of variation (CV) and standard deviation (SD) values, is an area of interest from which to consider an appropriate development strategy. METHODS: To characterize variability of Japanese data compared with non-Japanese data, the authors selected pharmaceutical products recently approved in Japan, reviewed their clinical trial data, and analyzed these data for efficacy response variables in Japan and Western countries. Twenty-nine products were selected for the examination. RESULTS: Japanese data are similar to non-Japanese data in terms of data variability, and the ratios of the Japanese to the non-Japanese values for CV and SD were within a relatively narrow range for most products. CONCLUSIONS: Japanese clinical trial data showed variability similar to that of non-Japanese data for most cases. It is expected that further studies to characterize specific regions in terms of clinical trial data will be conducted to consider an appropriate strategy for worldwide drug development.