Rapid Patient-Side Evaluation of Endothelial Glycocalyx Thickness in Healthy Sedated Cats Using GlycoCheck® Software

The endothelial glycocalyx (EG) determines transvascular fluid fluxes, and influences inflammation, coagulation, and capillary blood flow. The GlycoCheck® software calculates EG thickness using sidestream dark field videomicroscopy recordings. This method has not been evaluated for use in cats. The aim of the present study was to evaluate the use of GlycoCheck® for estimating EG thickness in healthy cats, and to investigate the variability of EG thickness in this population. One hundred and one healthy research-purposed cats were included in the study. The cats were sedated, and a handheld videomicroscope, connected to GlycoCheck® software, was used to evaluate the sublingual microvasculature. The parameters measured included perfused boundary region (PBR, an indirect measurement of EG thickness) in vessels between 5 and 25 μm in diameter, valid vessel density, percentage red blood cell filling, and median red blood cell column width. Heart rate, respiratory rate, pulse oximetry and oscillometric blood pressure readings were also recorded. There were 35 neutered male cats, 11 intact males, 38 neutered females, and 17 intact females. The average age was 63 months (range, 11–160 months). Tolerance intervals for PBR (vessel diameter 5–25 μm) were 1.89–3.00 μm (95% CI, lower limit 1.76–2.04, upper limit 2.83–3.13 μm); for valid vessel density were 73.33–333.33 μm/mm2 (95% CI, lower limit 77.00–99.33, upper limit 312.67–350.33 μm/mm2); for percentage red blood cell filling were 59.85–85.07% (95% CI, lower limit 58.97–63.33, upper limit 83.07–88.20 %); and for median red blood cell column width were 5.63–8.59 μm (95% CI, lower limit 5.28–6.07, upper limit 8.14–9.51 μm). There was a negative association between median red blood cell column width and body weight (p = 0.007). The median red blood cell column was significantly wider in intact females when compared to spayed females (p = 0.033). The GlycoCheck® analysis was easily performed in healthy sedated cats. Clinical variables did not have an effect on the EG thickness. These results suggest that this technique could be valuable for evaluation of the EG and microvascular parameters in cats.

Estimating the lower-limit of fracture toughness from ideal-strength calculations

Fracture mechanics is a fundamental topic to materials science.

Determination of Oxaliplatin by a UHPLC-MS/MS Method: Application to Pharmacokinetics and Tongue Tissue Distribution Studies in Rats

Oxaliplatin (OXP), a third-generation platinum-based chemotherapy drug, was often indirectly analyzed via total platinum by an ICP-MS because it was difficult to directly quantify using an LC-MS/MS method, due to its instability, bad column separability and severe MS signal inhibition. Here, we developed and validated a specific, sensitive and reproducible LC-MS/MS method for the quantification of OXP itself in rat plasma and tongue tissue on a SCIEX 4000 QTRAP® MS/MS system equipped with a Phenomenex Lux 5u Cellulose-1 column (250 × 4.6 mm, 5 μm). This method was validated at the lower limit of detection (LOD) and the lower limit of quantitation (LLOQ) of 5 ng/mL and 10 ng/mL, with linearity of 10–5000 ng/mL (r2 > 0.99) and 10–2500 ng/mL (r2 > 0.99), in rat plasma and tongue homogenates, respectively. The intra- and inter-day precision (CV%) and accuracy (RE%) were within 15% for LLOQ, low-, medium- and high-quality control samples. The mean extraction recoveries were around 50% and 80% for plasma and tongue homogenates, respectively. This assay was successfully applied to pharmacokinetics study following intravenous administration of OXP, as well as tongue tissue distribution after 1 h and 4 h of a novel oral mucosal patch application.

Fitting limit lines (envelope curves) to spreads of geoenvironmental data

Geoscientists frequently are interested in defining the overall trend in x- y data clouds using techniques such as least-squares regression. Yet often the sample data exhibits considerable spread of y-values for given x-values, which is itself of interest. In some cases, the data may exhibit a distinct visual upper (or lower) ‘limit’ to a broad spread of y-values for a given x-value, defined by a marked reduction in concentration of y-values. As a function of x-value, the locus of this ‘limit’ defines a ‘limit line’, with no (or few) points lying above (or below) it. Despite numerous examples of such situations in geoscience, there has been little consideration within the general geoenvironmental literature of methods used to define limit lines (sometimes termed ‘envelope curves’ when they enclose all data of interest). In this work, methods to fit limit lines are reviewed. Many commonly applied methods are ad-hoc and statistically not well founded, often because the data sample available is small and noisy. Other methods are considered which correspond to specific statistical models offering more objective and reproducible estimation. The strengths and weaknesses of methods are considered by application to real geoscience data sets. Wider adoption of statistical models would enhance confidence in the utility of fitted limits and promote statistical developments in limit fitting methodologies which are likely to be transformative in the interpretation of limits. Supplements, a spreadsheet and references to software are provided for ready application by geoscientists.

Note on “Parameters estimators of irregular right-angled triangular distribution”

Simple estimators were given in (Kachiashvili & Topchishvili, 2016) for the lower and upper limits of an irregular right-angled triangular distribution together with convenient formulas for removing their bias. We argue here that the smallest observation is not a maximum likelihood estimator (MLE) of the lower limit and we present a procedure for computing an MLE of this parameter. We show that the MLE is strictly smaller than the smallest observation and we give some bounds that are useful in a numerical solution procedure. We also present simulation results to assess the bias and variance of the MLE.

The lower limit for FEV1/FVC in dive medical assessments: a retrospective study

Introduction: Interpreting pulmonary function test (PFT) results requires a valid reference set and a cut-off differentiating pathological from physiological pulmonary function; the lower limit of normal (LLN). However, in diving medicine it is unclear whether an LLN of 2.5% (LLN-2.5) or 5% (LLN-5) in healthy subjects constitutes an appropriate cut-off. Methods: All PFTs performed at the Royal Netherlands Navy Diving Medical Centre between 1 January 2015 and 1 January 2021 resulting in a forced vital capacity (FVC), forced expiratory volume in one second (FEV1) and/or FEV1/FVC with a Z-score between -1.64 (LLN-5) and -1.96 (LLN-2.5) were included. Records were screened for additional tests, referral to a pulmonary specialist, results of radiological imaging, and fitness to dive. Results: Analysis of 2,108 assessments in 814 subjects showed that 83 subjects, 74 men and nine women, mean age 32.4 (SD 8.2) years and height 182 (7.0) cm, had an FVC, FEV1 and/or FEV1/FVC with Z-scores between -1.64 and -1.96. Of these 83 subjects, 35 (42%) underwent additional tests, 77 (93%) were referred to a pulmonary specialist and 31 (37%) underwent high-resolution CT-imaging. Ten subjects (12%) were declared ‘unfit to dive’ for various reasons. Information from their medical history could have identified these individuals. Conclusions: Use of LLN-2.5 rather than LLN-5 for FEV1/FVC in asymptomatic individuals reduces additional investigations and referrals to a pulmonary specialist without missing important diagnoses, provided a thorough medical history is taken. Adoption of LLN-2.5 could save resources spent on diving medical assessments and protect subjects from harmful side effects associated with additional investigations, while maintaining an equal level of safety.

Valproic Acid Concentrations in Mothers, Colostrum and Breastfed Infants during the Early Postpartum Period: Comparison with Concentrations Determined during Delivery and in the Mature Milk Period

To obtain information on the transport of valproic acid from mothers to colostrum and breastfed infants, in this cohort study, valproic acid concentrations in maternal serum (90 subjects), colostrum and the serum of breastfed infants were analyzed in years 1993–2018, between the 2nd and 5th postnatal days. Valproic acid concentrations ranged from 4.3 to 66.5 mg/L (mean 31.2 ± 13.6 mg/L) in maternal serum, from 0.5 to 5.9 mg/L (mean 1.1 ± 1.2 mg/L) in milk, and from 0.5 to 42.9 mg/L (mean 15.4 ± 9.4 mg/L) in infant serum. The milk/maternal serum concentration ratio ranged from 0.01 to 0.22 (mean 0.04 ± 0.04), and the infant/maternal serum concentration ratio ranged from 0.01 to 1.61 (mean 0.51 ± 0.28). A significant correlation was found between serum concentrations of breastfed infants and milk concentrations, maternal serum concentrations, maternal daily dose, and dose related to maternal body weight. Valproic acid concentrations in milk and infant serum did not reach the lower limit of the reference range used for the general epileptic population, and three-quarters of the concentrations in milk were lower than the lower limit of quantification. Routine monitoring of serum concentrations of breastfed infants is not necessary. If signs of potential adverse reactions are noted, serum concentrations of the infants should be measured.

Effectiveness and safety of pegylated liposomal doxorubicin versus epirubicin as neoadjuvant or adjuvant chemotherapy for breast cancer: a real-world study

Background Pegylated liposomal doxorubicin (PLD) is an improved formulation of doxorubicin with comparable effectiveness but significantly lower cardiotoxicity than conventional anthracycline. This study aimed to evaluate the real-world effectiveness and safety of PLD versus epirubicin as neoadjuvant or adjuvant treatment for breast cancer. Methods Clinical data of invasive breast cancer patients who received neoadjuvant or adjuvant chemotherapy with PLD or epirubicin were retrospectively collected. Propensity score matching (PSM) was performed to reduce the risk of selection bias. The molecular typing of these patients included Luminal A, Luminal B, HER2-positive, and basal-like/triple-negative. The primary outcome was pathological complete response (pCR) rate for neoadjuvant chemotherapy and 3-year disease-free survival (DFS) rate for adjuvant chemotherapy. Noninferiority was suggested if the lower limit of the 95% CI for the 3-year DFS rate difference was greater than − 10%. The secondary outcome was adverse reactions. Results A total of 1213 patients were included (neoadjuvant, n = 274; adjuvant, n = 939). pCR (ypT0/Tis ypN0) rates of patients who received neoadjuvant chemotherapy were 11.6% for the PLD group and 7.0% for the epirubicin group, but the difference was not statistically significant (P = 0.4578). The 3-year DFS rate of patients who received adjuvant chemotherapy was 94.9% [95%CI, 91.1–98.6%] for the PLD group and 95.4% [95%CI, 93.0–97.9%] for the epirubicin group (P = 0.5684). Rate difference between the two groups and its 95% CI was - 0.55 [− 5.02, 3.92]. The lower limit of the 95% CI was − 5.0% > − 10.0%, suggesting that PLD is not be inferior to epirubicin in adjuvant chemotherapy for breast cancer. The incidences of myelosuppression, decreased appetite, alopecia, gastrointestinal reactions, and cardiotoxicity were lower in the PLD group than in the epirubicin group, while the incidence of nausea was higher in the PLD group. Conclusions In the neoadjuvant and adjuvant treatment of breast cancer, effectiveness is similar but toxicities are different between the PLD-containing regimen and epirubicin-containing regimen. Therefore, further study is warranted to explore PLD-based neoadjuvant and adjuvant chemotherapy for breast cancer.