Higher Vd Research Articles

Absolute values of regional ventilation-perfusion mismatch in patients with ARDS monitored by electrical impedance tomography and the role of dead space and shunt compensation

BackgroundAssessment of regional ventilation/perfusion (V′/Q) mismatch using electrical impedance tomography (EIT) represents a promising advancement for personalized management of the acute respiratory distress syndrome (ARDS). However, accuracy is still hindered by the need for invasive monitoring to calibrate ventilation and perfusion. Here, we propose a non-invasive correction that uses only EIT data and characterized patients with more pronounced compensation of V′/Q mismatch.MethodsWe enrolled twenty-one ARDS patients on controlled mechanical ventilation. Cardiac output was measured invasively, and ventilation and perfusion were assessed by EIT. Relative V′/Q maps by EIT were calibrated to absolute values using the minute ventilation to invasive cardiac output (MV/CO) ratio (V′/Q-ABS), left unadjusted (V′/Q-REL), or corrected by MV/CO ratio derived from EIT data (V′/Q-CORR). The ratio between ventilation to dependent regions and perfusion reaching shunted units (VD′\\documentclass[12pt]{minimal} \\usepackage{amsmath} \\usepackage{wasysym} \\usepackage{amsfonts} \\usepackage{amssymb} \\usepackage{amsbsy} \\usepackage{mathrsfs} \\usepackage{upgreek} \\setlength{\\oddsidemargin}{-69pt} \\begin{document}$${\ ext{V}}_{{\ ext{D}}}^{\\prime }$$\\end{document}/QSHUNT) was calculated as an index of more effective hypoxic pulmonary vasoconstriction. The ratio between perfusion to non-dependent regions and ventilation to dead space units (QND/VDS′\\documentclass[12pt]{minimal} \\usepackage{amsmath} \\usepackage{wasysym} \\usepackage{amsfonts} \\usepackage{amssymb} \\usepackage{amsbsy} \\usepackage{mathrsfs} \\usepackage{upgreek} \\setlength{\\oddsidemargin}{-69pt} \\begin{document}$${\ ext{V}}_{{{\ ext{DS}}}}^{\\prime }$$\\end{document}) was calculated as an index of hypocapnic pneumoconstriction.ResultsOur calibration factor correlated with invasive MV/CO (r = 0.65, p < 0.001), showed good accuracy and no apparent bias. Compared to V′/Q-ABS, V′/Q-REL maps overestimated ventilation (p = 0.013) and perfusion (p = 0.002) to low V′/Q units and underestimated ventilation (p = 0.011) and perfusion (p = 0.008) to high V′/Q units. The heterogeneity of ventilation and perfusion reaching different V′/Q compartments was underestimated. V′/Q-CORR maps eliminated all these differences with V′/Q-ABS (p > 0.05). Higher VD′/QSHUNT\\documentclass[12pt]{minimal} \\usepackage{amsmath} \\usepackage{wasysym} \\usepackage{amsfonts} \\usepackage{amssymb} \\usepackage{amsbsy} \\usepackage{mathrsfs} \\usepackage{upgreek} \\setlength{\\oddsidemargin}{-69pt} \\begin{document}$$V_{D}^{\\prime } /Q_{SHUNT}$$\\end{document} correlated with higher PaO2/FiO2 (r = 0.49, p = 0.025) and lower shunt fraction (ρ = − 0.59, p = 0.005). Higher QND/VDS′\\documentclass[12pt]{minimal} \\usepackage{amsmath} \\usepackage{wasysym} \\usepackage{amsfonts} \\usepackage{amssymb} \\usepackage{amsbsy} \\usepackage{mathrsfs} \\usepackage{upgreek} \\setlength{\\oddsidemargin}{-69pt} \\begin{document}$$Q_{ND} /V_{DS}^{\\prime }$$\\end{document} correlated with lower PEEP (ρ = − 0.62, p = 0.003) and plateau pressure (ρ = − 0.59, p = 0.005). Lower values of both indexes were associated with less ventilator-free days (p = 0.05 and p = 0.03, respectively).ConclusionsRegional V′/Q maps calibrated with a non-invasive EIT-only method closely approximate the ones obtained with invasive monitoring. Higher efficiency of shunt compensation improves oxygenation while compensation of dead space is less needed at lower airway pressure. Patients with more effective compensation mechanisms could have better outcomes.

Strong contact resistance effects on vertical carrier density profile and surface trap density in WSe2 multilayers

Conducting channel migration depending on the thickness of 2D multilayers has been demonstrated theoretically and experimentally by ascribing it to the high interlayer barrier and thickness-dependent carrier mobility via an electrostatic gate and drain bias. However, the unique charge carrier transport feature is significantly suppressed when a high contact resistance is exhibited at the metal-to-2D semiconducting multilayers, in addition to the inherent tunneling barrier between neighboring layers. Herein, we report strong channel access contact resistance effects on the vertical carrier density profile and surface trap density along the thickness of WSe2 multilayer transistors. For the constructed top-contact electrodes demonstrating pseudo-ohmic behavior, we observed clear double humps in the second derivative of the transconductance (dgm) curves, implying conducting channel migration along the c-axis of the WSe2 multilayers, regardless of the drain bias (VD) conditions. Meanwhile, at the bottom-contact electrodes, demonstrating a relatively high contact resistance effect, the second hump of dgm exclusively appears at high VD regimes (3.0 V ≤ VD), signaling the restricted channel migration caused by poor contact quality, even in identical WSe2 multilayers. We further confirmed this distinct feature in dgm curves by connecting the top and bottom electrodes to support our observations. Furthermore, low-frequency noise measurements were performed to determine the surface trap density of the supporting dielectrics and the relevant carrier scattering mechanism. Our study provides valuable insight into the effects of contact resistance on carrier transport and the scattering mechanism in WSe2 multilayer transistors, shedding light on the optimization of device performance and contact quality.

Plasminogen Activator Inhibitor-1 and Vitamin D Association in the Overweight and Obese Pediatric Population.

Childhood overweight and obesity have been described by the World Health Organization as noncommunicable diseases and among the greatest public health threats since they have reached epidemic proportions. A child with obesity risks becoming an adult with obesity and developing metabolic and hemostatic disorders which are the basis for the development of coronary heart diseases. Recently, a number of clinical reports have demonstrated that both an increase in plasminogen activator inhibitor-1 (PAI-1) and a deficiency in 25OH-vitamin D3 (VD) are associated with an increase in thrombotic episodes. PAI-1 and VD levels were measured in 259 clinically overweight and obese children aged between 2 and 18 years enrolled in the Nutritional Education Program of the Bambino Gesù Children's Hospital and Research Institute of Rome (Italy) and 80 normal-weight subjects. We observed increased HOMA-IR, PAI-1, and other inflammation indices associated with decreased VD levels when compared to normal-weight children. Our results demonstrated that overweight and obesity are correlated with higher levels of the inflammation index. Moreover, our patients show high PAI-1 and low VD levels, confirming the high thrombotic risk in our pediatric population.

Semimechanistic pharmacokinetic-pharmacodynamic model of tripegfilgrastim for pediatric patients after chemotherapy.

Tripegfilgrastim is a long-acting granulocyte colony-stimulating factor (G-CSF) that has been used to prevent chemotherapy-induced neutropenia in adults. This study aimed to establish a pharmacokinetic (PK)-pharmacodynamic (PD) model to explore the impact of chemotherapy and tripegfilgrastim on absolute neutrophil counts (ANCs) and to further propose a fixed-dose regimen in pediatric patients. Because neutrophils affect the clearance of tripegfilgrastim, the semimechanistic PK-PD model was developed simultaneously by using data from 40 healthy adults and 27 pediatric patients with solid tumors. Tripegfilgrastim PK and ANC dynamics were described with a pharmacodynamics-mediated drug disposition model assuming quasi-equilibrium with five transit compartments mimicking neutrophil granulopoiesis. The effect of chemotherapy on neutrophils was included by stimulating the elimination of the G-CSF receptor at the mitotic cells. Healthy adult and pediatric patients showed significantly different value for dissociation constant of the tripegfilgrastim-G-CSF receptor complex (Kd ) and apparent volume of distribution (Vd /F). Patients treated with chemotherapy had a higher Vd /F and 62% lower Kd than healthy adults. As the age increased, the absorption rate of tripegfilgrastim was decreased. Body weight affected the G-CSF receptor-mediated internalization of tripegfilgrastim, and the baseline ANC value impacted the production rate of G-CSF receptors. Simulations from the developed model suggested that 1.5, 2.5, 4, and 6 mg single subcutaneous tripegfilgrastim doses for the respective weight groups of 10-20, 21-30, 31-44, and more than 45 kg significantly reduced the duration of Grade 4 neutropenia similar to tripegfilgrastim weight-based treatment with 100 μg/kg.

Study of the response of the microvascular bed to oxygen-helium therapy using high-frequency Doppler ultrasound in patients with COVID-19

Introduction. For the treatment of patients with hypoxemic form of respiratory failure, thermal oxygen-helium mixture (OHM) therapy is used.The aim of the work is to study the effect of OHM on the state of the microcirculatory bed in viral pneumonia caused by COVID-19 in patients with aggravated and unaggravated anamnesis.Materials and methods. There were 8 patients with an uncomplicated anamnesis, 11 with AH1–2 degree, 11 with AH1–2 degree and type II diabetes. The parameters of blood flow in the MVB were recorded with an ultrasound dopplerograph. OHM therapy (O2 – 30 %, He – 70 %, t=+95 ºС): 5 min breathing, 5 min rest – 3 cycles.Results. Before the OHM therapy, the level of «basic perfusion» was increased in group 3: significantly high Vs (p=0.02) and Vd (p=0.006), low RI (p=0.015) relative to group 1, this indicates a reduced vascular tone and venous congestion. After the OHM session in patients of group 1, the speed of Vs and Vd increased, the indices RI and PI decreased. In group 2 – Vs, Vd and Vam increased, RI decreased. The effect is long lasting. In group 3, the effect was noted on day 5, short-term. Conclusions. OHM therapy has a positive effect.

PTPRC, KDM5C, GABBR1 and HDAC1 are the Major Targets of Valproic Acid in Regulation of its Anticonvulsant Pharmacological Effects

Background: Valproic acid (VPA) is a small molecule which is the 3rd most prescribed drug among anticonvulsant therapeutics. Understanding of the pharmacology of VPA targets will help optimally rationalise the therapeutic effects and also minimise the undesired outcomes. Hence this study analysed the human specific targets of VPA and assessed the affinity of VPA to these targets to interpret potential safe therapeutic range for VPA. Materials and Methods: The targets of VPA were identified from the SwissTargetPrediction server and STITCH database and analysed for their affinity with VPA using Autodock vina 1.2.0. The volume of distribution (Vd, L) and the dose of VPA reported in the DrugBank database was used for estimation of the plasma and CSF concentration. The plasma and CSF Concentration Affinity (CA) ratio of VPA against each of the high affinity targets was assessed at variable Vd (0.1 to 0.4 L/kg) to identify the therapeutic safety window of VPA. Results: The plasma/CSF concentration of VPA range from 170 to 7000 μM and 17 to 700 μM respectively. The plasma concentration achieved was within the safety limits (170 to 700 μM) at higher Vd (&gt;10 L), while at lower Vd (&lt;10L), the plasma or CSF concentration achieved was of concern at VPA dose of &gt;1000 mg/day. The plasma concentration at very low Vd (&lt; 2L) was of concern even at dose of 500 mg/day. The affinity of VPA against all its human specific targets ranged from 2.9 to 52.1 mM. The CA ratio of VPA against its high affinity target was observed to be greater than 0.8, indicating potentially significant modulation of these targets. The following four targets showed CA ratio of over 1: PTPRC, KDM5C, GABBR1 and HDAC1, indicating their preferential targeting by VPA. CES1 and SLC22A12 are high affinity targets of VPA which can contribute to its undesired pharmacological effects (CNS oedema and hepatotoxicity). Conclusion: This study offers a novel insight into the anticonvulsant and undesired pharmacology of VPA by specifically identifying the targets involved and recommends an evidence-based approach to personalise dose titration of VPA to achieve optimal therapeutic benefits.

A database of modeled gridded dry deposition velocities for 45 gaseous species and three particle size ranges across North America

The dry deposition process refers to the flux loss of an atmospheric pollutant due to uptake of the pollutant by the earth's surfaces. Dry deposition flux of a chemical species is typically calculated as the product of its surface-layer concentration and its dry deposition velocity (Vd). Field measurement based Vd data are very scarce or do not exist for many chemical species considered in chemistry transport models. In the present study, gaseous and particulate dry deposition schemes were applied to generate a database of hourly Vd for 45 gaseous species and three particle size ranges for two years (2016–2017) at a 15 km by 15 km horizontal resolution across North America. Hourly Vd of the 45 gaseous species ranged from < 0.001 to 4.6 cm/sec across the whole domain, with chemical species-dependent median (mean) values being in the range of 0.018–1.37 cm/sec (0.05–1.43 cm/sec). The spatial distributions of the two-year average Vd showed values higher than 1–3 cm/sec for those soluble and reactive species over certain land types. Soluble species have the highest Vd over water surfaces, while insoluble but reactive species have the highest Vd over forests. Hourly Vd of PM2.5 across the whole domain ranged from 0.039 to 0.75 cm/sec with median (mean) value of 0.18 (0.20) cm s−1, while the mean Vd for PM2.5–10 is twice that of PM2.5. Uncertainties in the modeled Vd are typically on the order of a factor of 2.0 or larger, which needs to be considered when applying the dataset in other studies.

Bidirectional Mendelian Randomization Analysis for Vitamin D and Thyroid Peroxidase Antibody.

Purpose Whether Vitamin D deficiency or insufficiency is associated with thyroid autoimmunity was debated for long time. This study was still to explore the causal relationship of 25 (OH) D with a thyroid peroxidase antibody (TPOAb). Methods The data were obtained from a cross-sectional study, SPECT-China study, which was performed in 23 sites in East China during 2014 to 2016. 10636 participants were finally included in this study. Genotyped four 25 (OH) D-related and four TPOAb-associated single nucleotide polymorphisms (SNPs) created their genetic risk scores (GRS). Bidirectional mendelian randomization (MR) analysis was used in this study. Results 25 (OH) D GRS was significantly associated with 25 (OH) D (B −0.093, 95% CI −0.111, −0.074) and TPOAb level (B 0.067, 95% CI 0.002 to 0.132). TPOAb GRS was significantly associated with TPOAb concentration (B 0.345, 95% CI 0.135 to 0.556), but not 25 (OH) D (B −0.030, 95% CI −0.091 to 0.030). Using 25 (OH) D_GRS as instrumental variable in the MR analysis, a causal relationship of genetically determined 25 (OH) D with increased TPOAb concentration (B −0.720, 95% CI −1.429 to −0.012). No relation was found between genetically instrumented TPOAb and 25 (OH) D. Conclusion A higher VD_GRS was associated with higher risk of increased TPOAb concentration, which supports a causal association between decreased vitamin D and increased concentration of TPOAb in an eastern Chinese population.

Synthesis, Characterization, and Antimicrobial Evaluation of new Ibuprofen Derivatives

A new series of ibuprofen derivatives were synthesized and tested against the microbial activity. P_amino ethyl benzoate (compound I) was prepared, then coupled with ibuprofen acyl chloride (compound II) to give ethyl 4-(2-(4-isobutylphenyl) propanamido) benzoate (compounds III). Hydrazine hydrate 99% was added to compound III to synthesized N-(4-(hydrazinecarbonyl) phenyl)-2-(4-isobutylphenyl) propenamide (compound IV). Finally compound IV coupled with different aldehydes (1. Benzaldehyde (Va) 2. Salicylaldehyde (Vb) 3. 4_hydroxybenzaldehyde (Vc) 4. Vanillin (Vd) respectively to form target compounds. Identifications and characterization of these compounds were done by using Fourier Transform Infrared Spectroscopy (FTIR), and 1 HNMR analyses. The antimicrobial results showed that compounds (Va has low activity, Vd has high active, Vb and Vd has the moderate activity) against gram positive bacteria (Staphylococcus aureus and Streptococcus pyogenes) and gram-negative bacteria (Escherichia coli and Pseudomonas aeruginosa) at concentration 500 µg/mL. Vd was the only compound that has antifungal activity against Candida ablicans compared to fluconazole. Keywords: Anti-microbial activity, Ibuprofen, Hydrazine hydrate, Schiff base, Aldehyde.

Extension of a gaseous dry deposition algorithm to oxidized volatile organic compounds and hydrogen cyanide for application in chemistry transport models.

The dry deposition process refers to flux loss of an atmospheric pollutant due to uptake of the pollutant by the Earth’s surfaces, including vegetation, underlying soil, and any other surface types. In chemistry transport models (CTMs), the dry deposition flux of a chemical species is typically calculated as the product of its surface layer concentration and its dry deposition velocity (Vd); the latter is a variable that needs to be highly empirically parameterized due to too many meteorological, biological, and chemical factors affecting this process. The gaseous dry deposition scheme of Zhang et al. (2003) parameterizes Vd for 31 inorganic and organic gaseous species. The present study extends the scheme of Zhang et al. (2003) to include an additional 12 oxidized volatile organic compounds (oVOCs) and hydrogen cyanide (HCN), while keeping the original model structure and formulas, to meet the demand of CTMs with increasing complexity. Model parameters for these additional chemical species are empirically chosen based on their physicochemical properties, namely the effective Henry’s law constants and oxidizing capacities. Modeled Vd values are compared against field flux measurements over a mixed forest in the southeastern US during June 2013. The model captures the basic features of the diel cycles of the observed Vd. Modeled Vd values are comparable to the measurements for most of the oVOCs at night. However, modeled Vd values are mostly around 1 cm s−1 during daytime, which is much smaller than the observed daytime maxima of 2–5 cm s−1. Analysis of the individual resistance terms and uptake pathways suggests that flux divergence due to fast atmospheric chemical reactions near the canopy was likely the main cause of the large model–measurement discrepancies during daytime. The extended dry deposition scheme likely provides conservative Vd values for many oVOCs. While higher Vd values and bidirectional fluxes can be simulated by coupling key atmospheric chemical processes into the dry deposition scheme, we suggest that more experimental evidence of high oVOC Vd values at additional sites is required to confirm the broader applicability of the high values studied here. The underlying processes leading to high measured oVOC Vd values require further investigation.

Comparative Efficacy of Metformin vs. Pioglitazone alone and in Combination with High Dose Oral Cholecalciferol among Women with Polycystic Ovary Syndrome (PCOS): A Six-month Randomized, Open Label Study

Purpose: We aimed to evaluate the comparative efficacy of metformin and pioglitazone coadministered with high dose VD on clinical, biochemical, hormonal and insulin sensitivity parameters in women with PCOS. Material and Methods: In this open label randomised study, a total of 136 women, aged 18-40 years, diagnosed with PCOS as per the AE PCOS 2009 criteria, were randomly assigned into four groups (n=34 per group). The four groups received Metformin-1gm/day alone, metformin-1gm/day+cholecalciferol4000IU/ d,pioglitazone-30mg/day alone and pioglitazone- 30mg/day+cholecalciferol-4000IU/d.The clinical, biochemical, hormonal and insulin sensitivity parameters were evaluated at 0, 3 months and 6 months after the intervention. Results: The mean age of subjects was 21.89±4.99 years with mean BMI of 22.19±3.24kg/m2. The mean serum 25OHD level at the baseline in the metformin+VD and pioglitazone+VD group was 13.28±8.44ng/ml and 11.17±7.46ng/ml and it improved to 63.33±19.76ng/ml and 57.69±14.43ng/ ml respectively after six months of intervention. The mean no. of cycles/year and Ferriman-Gallwey (FG) score improved in all four arms. Significant decrease in the total serum testosterone level was observed in the groups that received VD in addition to metformin and pioglitazone, the effect being more significant in the metformin+VD group (64.60±23.59ng/dl at 0 months to 41.24±12.83ng/dl after 6 months). Plasma glucose and insulin levels from a two-hour OGTT showed a significant improvement in subjects receiving VD in addition to pioglitazone. Conclusion: Metformin and pioglitazone are equally efficacious for treatment of women with PCOS. High dose oral cholecalciferol co-administration significantly improved the metabolic outcomes among these women. Key words: Metformin; Pioglitazone; PCOS; Insulin resistance; Vitamin D deficiency.

Convection-Enhanced Arborizing Catheter System Improves Local/Regional Delivery of Infusates Versus a Single-Port Catheter in Ex Vivo Porcine Brain Tissue.

Standard treatment for glioblastoma is noncurative and only partially effective. Convection-enhanced delivery (CED) was developed as an alternative approach for effective loco-regional delivery of drugs via a small catheter inserted into the diseased brain. However, previous CED clinical trials revealed the need for improved catheters for controlled and satisfactory distribution of therapeutics. In this study, the arborizing catheter, consisting of six infusion ports, was compared to a reflux-preventing single-port catheter. Infusions of iohexol at a flow rate of 1 μL/min/microneedle were performed, using the arborizing catheter on one hemisphere and a single-port catheter on the contralateral hemisphere of excised pig brains. The volume dispersed (Vd) of the contrast agent was quantified for each catheter. Vd for the arborizing catheter was significantly higher than for the single-port catheter, 2235.8 ± 569.7 mm3 and 382.2 ± 243.0 mm3, respectively (n = 7). Minimal reflux was observed; however, high Vd values were achieved with the arborizing catheter. With simultaneous infusion using multiple ports of the arborizing catheter, high Vd was achieved at a low infusion rate. Thus, the arborizing catheter promises a highly desirable large volume of distribution of drugs delivered to the brain for the purpose of treating brain tumors.

Black titanium oxynitride thin films prepared by nitrogen plasma-assisted pulsed laser deposition for flat-panel displays

Preference for a classy black turn-off appearance and for distinct dark colors on flat-panel displays has led to a high demand for optically black materials. Titanium oxynitrides and tungsten-doped oxynitrides were prepared using nitrogen plasma assisted pulsed laser deposition, and their optical absorption properties were investigated. A selection of Ti-O-N films were prepared with different compositions by controlling the emission current (Ie) and discharge voltage (Vd) of the ion source. It was found that the nitrogen content of the Ti(O,N)x could be adjusted by controlling the Ie. The large, flat absorption coefficient of approximately 40 μm−1 in the visible range (400–700 nm) attained for the samples deposited at high Vd was attributed to tungsten doping from a W filament in the ion source. The 4.1 mol%W-doped Ti(O,N)x, which had a rock-salt-type structure, was optically jet-black. The origin of the flat wavelength dispersion in the W-doped Ti(O,N)x was attributed to the coexistence of semiconducting absorption and metallic absorption mechanisms. DFT calculations suggest that the 5d states achieved when using doped tungsten provide high absorption in the mid-wavelength range, whereas undoped-Ti(O,N)x was characterized by weak absorption.

Reduction in minute alveolar ventilation causes hypercapnia in ventilated neonates with respiratory distress.

Hypercapnia occurs in ventilated infants even if tidal volume (VT) and minute ventilation (VE) are maintained. We hypothesised that increased physiological dead space (Vd,phys) caused decreased minute alveolar ventilation (VA; alveolar ventilation (VA) × respiratory rate) in well-ventilated infants with hypercapnia. We investigated the relationship between dead space and partial pressure of carbon dioxide (PaCO2) and assessed VA. Intubated infants (n = 33; mean birth weight, 2257 ± 641 g; mean gestational age, 35.0 ± 3.3 weeks) were enrolled. We performed volumetric capnography (Vcap), and calculated Vd,phys and VA when arterial blood sampling was necessary. PaCO2 was positively correlated with alveolar dead space (Vd,alv) (r = 0.54, p < 0.001) and Vd,phys (r = 0.48, p < 0.001), but not Fowler dead space (r = 0.14, p = 0.12). Normocapnia (82 measurements; 35 mmHg ≤ PaCO2 < 45 mmHg) and hypercapnia groups (57 measurements; 45 mmHg ≤ PaCO2) were classified. The hypercapnia group had higher Vd,phys (median 0.57 (IQR, 0.44–0.67)) than the normocapnia group (median Vd,phys/VT = 0.46 (IQR, 0.37–0.58)], with no difference in VT. The hypercapnia group had lower VA (123 (IQR, 87–166) ml/kg/min) than the normocapnia group (151 (IQR, 115–180) ml/kg/min), with no difference in VE.Conclusion: Reduction of VA in well-ventilated neonates induces hypercapnia, caused by an increase in Vd,phys.What is Known: • Volumetric capnography based on ventilator graphics and capnograms is a useful tool in determining physiological dead space of ventilated infants and investigating the cause of hypercapnia.What is New:• This study adds evidence that reduction in minute alveolar ventilation causes hypercapnia in ventilated neonates.

Effects of the leaf functional traits of coniferous and broadleaved trees in subtropical monsoon regions on PM2.5 dry deposition velocities

Plants can intercept airborne particulate matter through deposition. Different types of plants exhibit different functional leaf traits, which can affect the dry deposition velocity (Vd). However, the most crucial leaf traits of coniferous and broadleaved trees remain unidentified. In this study, we selected 18 typical plants from the subtropical monsoon regions, where PM2.5 (fine particulate matter with a diameter of ≤2.5 μm) concentrations are relatively high, and classified them into coniferous and broadleaved categories. Subsequently, we analyzed the relationships between Vd and leaf surface free energy (SFE), single leaf area (LAs), surface roughness (SR), specific leaf area (SLA), epicuticular wax content (EWC), and width-to-length ratio (W/L). The results indicated that most coniferous trees exhibited a high Vd. The correlation analysis revealed that SFE, SR, LAs, and W/L were the key factors that affected the Vd of all the tested species. SFE and SLA had the strongest influence on the Vd of broadleaved trees, whereas LAs and SLA had the strongest effect on that of coniferous trees. Most coniferous trees had a high SLA, which can reduce water loss and hinder particle deposition. However, the stiff leaves of coniferous trees fluttered less, resulting in a larger leaf area that enhanced the capture efficiency. The leaf structure of broadleaved trees is more flexible, resulting in erratic flutter, which may impede deposition and lead to high resuspension. Coniferous and broadleaved trees may have different dominant leaf traits that affect particle deposition.

Aminoglycoside Dosing and Volume of Distribution in Critically Ill Surgery Patients.

Background: At a tertiary referral and Level I trauma center, current institutional guidelines suggest initial aminoglycoside doses of gentamicin or tobramycin 4 mg/kg and amikacin 16 mg/kg for patients admitted to surgical intensive care units (SICUs) with suspected gram-negative infection. The objective of this study was to evaluate initial aminoglycoside dosing and peak serum drug concentrations in critically ill surgery patients to characterize the aminoglycoside volume of distribution (Vd) and determine an optimal standardized dosing strategy. Methods: This retrospective, observational, single-center study included adult SICU patients who received an aminoglycoside for additional gram-negative coverage. Descriptive statistics were used to evaluate the patient population, aminoglycoside dosing, and Vd. Multivariable linear regression was applied to determine variables associated with greater aminoglycoside Vd. The mortality rate was compared in patients who achieved adequate initial peak concentrations versus those who did not. Results: One hundred seventeen patients received an aminoglycoside in the SICUs, of whom 58 had an appropriately timed peak concentration measurement. The mean Acute Physiology, Age, and Chronic Health Evaluation (APACHE) II score was 27.8 ± 8.9. The Vd in patients receiving gentamicin, tobramycin, and amikacin was 0.49 ± 0.10, 0.41 ± 0.09, and 0.53 ± 0.13 L/kg, respectively. Together, the mean aminoglycoside Vd was 0.50 ± 0.12 L/kg. Gentamicin or tobramycin 5 mg/kg achieved goal peak concentrations in 24 patients (63.2%), and amikacin 20 mg/kg achieved the desired concentrations in nine patients (50.0%). Net fluid status, Body Mass Index, and vasopressor use were not predictive of Vd. There was no difference in the in-hospital mortality rate in patients who achieved adequate peak concentrations versus those who did not (26.8% versus 26.7%; p = 0.99). Conclusion: High aminoglycoside doses are needed in critically ill surgery patients to achieve adequate initial peak concentrations because of the high Vd. Goal peak concentrations were optimized at doses of gentamicin or tobramycin 5 mg/kg, and amikacin 20 mg/kg.

Vancomycin Area under the Curve and Pharmacokinetic Parameters during the First 24 Hours of Treatment in Critically Ill Patients using Bayesian Forecasting.

BackgroundCurrently, the achievement of the target area under the curve (AUC)/minimum inhibitory concentration ratio during the first 24 - 48 h of treatment is associated with reduced 30-day mortality and greater microbiological eradication in patients with methicillin-resistant Staphylococcus aureus bacteremia. This study aimed to determine the AUC and pharmacokinetic parameters on the first day of vancomycin administration based on the Bayesian theorem to optimize the dosing regimen in critically ill patients.Materials and MethodsThis retrospective study included participants meeting the following criteria: 1) ≥18 years old; 2) receipt of at least one dose of vancomycin; 3) measurement of 2 vancomycin serum concentrations during the first 24 h of treatment; and 4) an intensive care unit admission, mechanical ventilator use, or an Acute Physiology and Chronic Health Evaluation II score >15 points. The AUC on day 1 of treatment and the estimated vancomycin pharmacokinetic parameters were measured using PrecisePK software based on the Bayesian theorem.ResultsWe obtained 132 vancomycin concentrations from 66 patients. The vancomycin pharmacokinetic parameters were as follows: AUC0-24, 571.09 (± standard deviation [SD] 188.62) mg/L·h; clearance (CL), 2.97 (± SD 1.81) L/h; volume of distribution (Vd), 50.60 (± SD 13.91) L; elimination rate constant, 0.062 (± SD 0.039) h−1; and half-life, 18.19 (± SD 15.96) h. Focusing on the vancomycin loading dose, AUC0-24 400 - 600 was achieved in 41.7, 46.1, 44.4, and 26.3% of patients with loading doses of <20, 20 – 24.9, 25 – 30, and >30 mg/kg, respectively. Whereas AUC0-24 ≥521 was achieved in 50, 50, 77.8, and 84.2% of patients with loading doses of <20, 20 – 24.9, 25 – 30, and >30 mg/kg, respectively. The CL of vancomycin was correlated with creatinine CL, whereas the Vd of vancomycin was significantly correlated with age and body weight.ConclusionThis study revealed that the higher Vd and CL values on the first day of vancomycin therapy were found in critically ill patients. Additionally, a higher vancomycin loading dose (25 – 30 mg/kg) might be required to achieve target of AUC0-24 during early phase of administration for critically ill patients.

Stroma-normalised vessel density predicts benefit from adjuvant fluorouracil-based chemotherapy in patients with stage II/III colon cancer

BackgroundIdentification of biomarkers associated with benefit of adjuvant chemotherapy in stage II/III colon cancer is an important task.MethodsVessel density (VD) and tumour stroma were analysed in a randomised-trial-derived discovery cohort (n = 312) and in a stage II/III group of a population-based validation cohort (n = 85). VD was scored separately in the tumour centre, invasive margin and peritumoral stroma compartments and quantitated as VD/total analysed tissue area or VD/stroma area.ResultsHigh stroma-normalised VD in the invasive margin was associated with significantly longer time to recurrence and overall survival (OS) (p = 0.002 and p = 0.006, respectively) in adjuvant-treated patients of the discovery cohort, but not in surgery-only patients. Stroma-normalised VD in the invasive margin and treatment effect were significantly associated according to a formal interaction test (p = 0.009). Similarly, in the validation cohort, high stroma-normalised VD was associated with OS in adjuvant-treated patients, although statistical significance was not reached (p = 0.051).ConclusionThrough the use of novel digitally scored vessel-density-related metrics, this exploratory study identifies stroma-normalised VD in the invasive margin as a candidate marker for benefit of adjuvant 5-FU-based chemotherapy in stage II/III colon cancer. The findings, indicating particular importance of vessels in the invasive margin, also suggest biological mechanisms for further exploration.

A Prospective Evaluation of Serum Vitamin D (1, 25(OH)2 D3) and Endogenous Sex Hormone Levels in Colorectal Cancer Patients.

Background: Data on 25-OH VD concentrations and the associated factors in colorectal cancer (CRC) patients are scarce and need to be investigated.Methods: A total of 200 CRC patients participated in this cross-sectional study conducted in Pakistan. Socio-demographic and other health data were collected in a pretested questionnaire. Serum measurements of Vitamin D (1, 25(OH)2 D3) levels and hormones were performed. Association of age, sex, primary site, effects of hormone therapy and stage of disease and selected reproductive health indicators on vitamin D status were primarily scrutinized by univariate analysis.Results: Mean age of the population was 55.3 years (±15.6; Range: 20–90 years). Estradiol concentration was considerably elevated in young females compared to young male patients (p < 0.001). The concentrations of FSH, LH testosterone and estradiol were significantly lower in post-menopausal female CRC patients as compared to their male counterparts of old age (p, for all trends < 0.05). Both LH and FSH showed significant gender difference but only in older patients. Level of estrogen was markedly decreased in older post-menopausal CRC patients compared to premenopausal CRC patients, which might be associated with CRC progression. In the group of women, who “ever used hormone therapy” had differences of statistical significance (p, for all trends < 0.05) in their mean serum 25-OH VD concentrations, while in the group of women who “never used hormone therapy” had non-significant differences in their mean serum 25-OH VD concentrations (p, for all trends > 0.05). High 25-OH VD concentrations were observed in women who had their menarche at the age of 15 years or more. Nulliparous women had the highest mean 25-OH VD concentrations as compared to unparious or multiparious women. In addition, women having their menopause at 40–44 years of age had the highest 25-OH VD concentrations, although the difference was not significant (p = 0.08). Women who “never used any oral contraceptive” had higher 25-OH VD concentrations as compared to those “whoever used oral contraceptives.”Conclusion: Our findings suggest that vitamin D has a positive effect on the development of CRC through the mediation of hormones. Other health and reproductive traits that affect hormone levels may have an indirect effect on the development of CRC. Further potential studies that directly evaluate levels of circulating hormones and hormone therapy in women in association to 25-OH VD concentrations, as well as their possible role in colorectal cancer risk, would be vastly edifying.

Laser-induced fluorescence measurements of acceleration zone scaling in the 12.5 kW HERMeS Hall thruster

We present laser-induced fluorescence measurements of acceleration zone scaling with discharge voltage (Vd), magnetic field strength (B), and facility background pressure (PBG) in NASA’s 12.5 kW Hall Effect Rocket with Magnetic Shielding. At fixed discharge current, the plasma potential profiles at discharge voltages from 300 to 600 V approximately overlapped in the region with plasma potential less than 300 V; ion acceleration began further upstream at higher Vd because the region with a steep potential gradient was broader. The radial divergence of mean ion velocity vectors in the outer half of the channel and near plume increased with decreasing Vd. At fixed Vd, the acceleration zone was located further upstream at higher B and at higher PBG. Bimodal ion velocity distribution functions (IVDFs) were measured along the channel centerline in the acceleration zone at high discharge voltages; this effect was attributed to time-averaging over movement of the acceleration zone during large-amplitude discharge current oscillations. At lower discharge voltages, the broadening of the IVDFs in the near plume could not be fully explained by ionization within the acceleration region. These results have implications for understanding front pole erosion, which can be an important wear mechanism over the long lifetimes of magnetically shielded thrusters, and they provide baseline data for validating first principles models of cross-field electron transport.