Geometric Concentrations Research Articles

First-in-Human Phase I Clinical Trial of the Adenosine A1R/A3R Agonist AST-004 in Healthy Subjects.

AST-004 is a small-molecule adenosine A1/A3 receptor agonist that has exhibited significant cerebroprotective efficacy in preclinical models of acute ischemic stroke and traumatic brain injury. The primary objectives of this clinical phase I first-in-human study were to evaluate the safety and tolerability profile of single ascending intravenous doses in healthy subjects. The secondary objectives were to characterize the single-dose pharmacokinetic profiles in plasma, cerebrospinal fluid (CSF), and urine. In part 1 of the study, AST-004 was administered in ascending dose cohorts of 5, 25, 50, 75, and 100 mg, with 6 subjects in each cohort receiving the study drug and 2 receiving placebo. In part 2, all 12 subjects received a 100 mg IV infusion of the study drug followed by a single CSF collection per subject via lumbar puncture at 20, 40, or 60 minutes after infusion. A total of 42 subjects received AST-004, with no severe or serious adverse events observed. Twelve of these subjects experienced a treatment-emergent adverse event, the most frequent across groups being headache. In part 2, pharmacokinetic analyses confirmed that AST-004 was distributed in the CSF, with the CSF-to-plasma ratio increasing over the 3 timepoints sampled. The mean half-life was 1.1 to 1.4 hours for doses of 25 to 100 mg, and the geometric mean maximum plasma concentration obtained in the highest dosing cohort (100 mg) was 2232±428 ng/mL. AST-004 was safe and well-tolerated at plasma concentrations 3 to 8× higher than those associated with significant efficacy in astrocyte's preclinical primate stroke efficacy studies, with CSF concentrations highest at the 60-minute collection timepoint, the last timepoint tested. This study supports additional clinical investigations, including evaluation of an extended infusion to support the phase 2 program in stroke and traumatic brain injury.

Omiganan-Based Synthetic Antimicrobial Peptides for the Healthcare of Infectious Endophthalmitis.

Bacterial endophthalmitis is a severe infection of the aqueous or vitreous humor of the eye that can lead to permanent vision loss. Due to the rapid emergence of antibiotic resistance and dose-limiting toxicities, the standard treatment of bacterial endophthalmitis via the intravitreal injection of broad-spectrum antibiotics remains inadequate. Membrane active cationic antimicrobial peptides (AMPs) have emerged as a promising class of effective and broad-spectrum antimicrobial agents with potential to overcome antibiotic resistance. In this work, we investigate, for the first time, the use of omiganan (IK-12), a 12-amino acid indolicidin derivative for the treatment of bacterial endophthalmitis. Additionally, IK-12 was used as a template to perform amino acid rearrangements, without altering the length or type of amino acids, to yield a series of new derivative AMPs with varying extents of secondary structure formation under membrane mimicking conditions. IK-12 and its derivatives demonstrated strong and broad-spectrum antibacterial activities against a panel of clinically isolated Gram-positive and Gram-negative bacteria, including methicillin-resistant Staphylococcus aureus commonly implicated in bacterial endophthalmitis. Interestingly, two of the new IK-12 derivatives, IP-12 and WP-12, showed lower geometric mean minimum inhibitory concentration and higher 50% hemolysis concentration values, which effectively translated into 2- to 3.4-fold higher bacterial selectivity than the parent IK-12. Furthermore, the intravitreal injection of IK-12, IP-12, and WP-12 in a rabbit model of MRSA-induced endophthalmitis led to considerably improved clinical presentation and reduced recruitment of inflammatory cells. In all, these results demonstrate the potential of IK-12 and its derivatives, IP-12 and WP-12, as promising candidates for the treatment of bacterial endophthalmitis.

Associations of body composition measures with circulating insulin-like growth factor-I, testosterone, and sex hormone-binding globulin concentrations in 16,000 men.

Adiposity is positively associated with risk of some cancer sites and other health conditions in men; however, it is unclear if endogenous hormones play a role in these associations. We examined how body composition, measured from magnetic resonance imaging (MRI) and common measures of adiposity (e.g., body mass index (BMI)), are related to hormone concentrations in men from the UK Biobank study. Up to 16,237 men with available body composition data (including visceral, subcutaneous, and liver fat, muscle fat infiltration (MFI), lean tissue, and common adiposity measures) and serum hormone measurements (insulin-like growth factor-I (IGF-I), total testosterone, sex hormone-binding globulin (SHBG), and calculated free testosterone) were included. Multivariable-adjusted linear regression models were used to determine the geometric mean hormone and SHBG concentrations across categories of each exposure. Common measurements of adiposity were highly correlated with MRI measures of central and total adiposity (r = 0.76-0.91), although correlations with ectopic fat (liver fat and MFI) were lower (r = 0.43-0.54). Most adiposity measurements showed an inverse U- or J-shaped association with circulating IGF-I and free testosterone; however, MFI was linearly inversely associated, and lean tissue volume was positively associated with both IGF-I and free testosterone concentrations. All body composition measures were inversely associated with total testosterone and SHBG concentrations (relative geometric mean difference between Q5 vs. Q1: 20-30%). Our results show that common adiposity and most MRI measures of adiposity relate similarly to serum hormone concentrations; however, associations with ectopic fat (particularly MFI) and lean tissue were different.

Advanced optimization of elastic sheets for solar parabolic trough concentrators: integrating particle swarm optimization and genetic algorithms

Abstract The fabrication of solar parabolic trough concentrators using flat elastic sheets presents a straightforward and cost-effective method. This paper introduces an optimization technique centered on stiffness adjustment, harnessing elastic buckling to attain precise parabolic shapes in these concentrators. Through an enhanced Particle Swarm Optimization-Genetic Algorithm (PSO-GA), strategically punched holes are optimized on the flat sheet, allowing for the attainment of perfect parabolic shapes by controlling the chord length with a positional rod or cable. The efficacy of this approach is showcased not only through interactive finite element analysis and ray tracing software simulations but also via experimental sunlight concentration. A geometric concentration ratio of up to 145.16 is achieved, underscoring the effectiveness of this innovative concept. This approach facilitates the simple fabrication and transportation of flat mirror elements to field sites, where they can be assembled into parabolic trough concentrators, offering potential cost reductions and highly efficient solar energy solutions.

8548 Breast Development in Infant Girls: Does Endogenous Estrogen Production During Minipuberty Play a Role?

Abstract Disclosure: M. Goldberg: None. S. Zhao: None. A. Kelly: None. V.A. Stallings: None. D.M. Umbach: None. W.J. Rogan: None. N. Shaw: None. D.P. Sandler: None. Background: Breast tissue, present at birth in most term infants, regresses during infancy but persists longer in girls than boys. In girls, this persistence is thought to be due in part to stimulation by estradiol (E2) produced during minipuberty, the postnatal activation of the hypothalamic-pituitary-gonadal axis. Empirical data are sparse, however. Because E2 concentrations in infant girls fluctuate, repeated E2 measures may be necessary to adequately characterize production across minipuberty and to detect effects on estrogen-sensitive breast tissue. Hypothesis: Higher average exposure to E2 during minipuberty is associated with larger breast bud diameter in late infancy in term females. Methods: We leveraged data from 136 girls from the Infant Feeding and Early Development (IFED) Study, a prospective cohort of reproductive development in term infants enrolled during 2010-2013 from the Philadelphia area. We measured E2 in serum samples collected at study visits every 2-4 weeks from age 2-32 weeks. We assessed breast bud diameter via ultrasound at the 32-week visit. For data analysis, we log2-transformed both E2 and breast bud diameter. For E2 concentrations below the limit of detection (2.99 pg/mL, 35% of samples), we applied multiple imputation. We first calculated the intraclass correlation coefficient (ICC) of repeated E2 to understand the relative magnitude of total variation from within subjects. We then calculated subject-specific mean of E2 across time and estimated associations with breast bud diameter at the 32-week visit using both age- and multivariable-adjusted linear regression models. We present results as percent change in breast bud diameter per doubling in average E2 concentration ([2β-1] x 100%). Results: Most infants were Black (71%) and formula-fed (76%). The median number of E2 measures per girl was 9 (range: 5-10). Most of the variation in E2 concentrations was due to within-individual variation (ICC=0.27). The geometric mean E2 concentration from 2-32 weeks of age was 5.1 pg/mL (95% confidence interval [CI]: 4.7-5.4). The median breast bud diameter at the 32-week visit was 13.7mm (range: 4.4-30.5). A doubling in average E2 concentration across minipuberty was associated with a 26% larger breast bud diameter (95% CI 10-43%). This association was similar after adjustment for feeding method, race, gestational age, neonatal weight, and breast bud diameter at the neonatal visit (percent change: 28%, 95% CI: 12-46%). Conclusions: Our results suggest that endogenous estrogen production in females during minipuberty stimulates the infant breast bud. More research is needed to investigate the potential biologic relevance of this hormonal stimulation of infant breast tissue to later breast development and risk of malignant and benign breast disorders. Presentation: 6/1/2024

Safety, immunogenicity, and optimal dosing of a modified vaccinia Ankara-based vaccine against MERS-CoV in healthy adults: a phase 1b, double-blind, randomised placebo-controlled clinical trial.

MERS-CoV is a respiratory pathogen with a case-fatality rate of 36%, and for which no vaccines are currently licensed. MVA-MERS-S is a candidate vaccine based on recombinant modified vaccinia virus Ankara (MVA). In this study, the safety, immunogenicity, and optimal dose schedule of MVA-MERS-S was assessed in individuals with previous exposure to SARS-CoV-2 infections and vaccines. We conducted a multicentre, double-blind, randomised controlled phase 1b clinical trial at two university medical centres in Germany and the Netherlands. Healthy volunteers aged 18-55 years were assigned by computer randomisation to receive three intramuscular injections of 107 or 108 plaque-forming units (PFU) of MVA-MERS-S, with two treatment groups each of either 28-day or 56-day intervals between the initial two doses, and one control arm that received only placebo, at a ratio of 2:2:2:2:1. The third dose was given after 224 days. The sponsor, clinical and laboratory staff, and participants were masked to both vaccine dose and dosing interval. The primary outcome was safety, assessed in the all participants who had received at least one injection; daily solicited vaccine reactions were recorded after each dose for 7 days, unsolicited adverse events for 28 days, and serious adverse events throughout the study. The secondary outcome was humoral immunogenicity, measured with vaccine-induced geometric mean antibody concentrations and seroconversion rates, analysed in all participants who received at least three allocated treatments. This study is registered at ClinicalTrials.gov (NCT04119440) and is completed. Between 26 July, 2021, and 3 March, 2022, 244 volunteers were screened, 177 of whom were eligible and 140 were randomly assigned either to the 28-day 107 PFU group (n=32), 56-day 107 PFU group (n=31), 28-day 108 PFU group (n=31), 56-day 108 PFU group (n=30), or placebo group (n=16). In total, 178 doses were administered of 107 PFU of MVA-MERS-S, 174 of 108 PFU, and 164 doses of placebo, and 139 participants received at least one injection. 73 (53%) were female and 66 (48%) were male. No serious vaccine-related adverse events occurred. Solicited local reactions were mild in 288 (93%, 95% CI 90-96) of 309 reports and consisted primarily of pain or tenderness. Pain or tenderness (of any severity) occurred after 69 (39%, 32-46) of 178 107 PFU injections, 138 (79%; 73-85) of 174 108 PFU injections, and 18 (11%; 7-11) of 164 placebo injections. Of 595 reported solicited systemic reactions, 479 (81%, 77-83) were graded as mild. Systemic reactions of any grade occurred after 77 (43%; 36-51) 107 PFU injections, 102 (59%; 51-66) 108 PFU injections, and 67 (41%; 34-49) of 164 placebo injections. At 28 days after the second dose, MERS-CoV neutralising antibodies were highest for participants assigned to 56-day 108 PFU, with geometric mean ratios of 7·2 (95% CI 3·9-13·3) for the 56-day 108 PFU group versus the 28-day 108 PFU group (p<0·0001), 3·9 (2·1-7·2) for the 56-day 108 PFU group versus the 56-day 107 PFU group (p=0·0031), and 5·4 (2·9-10·0) for the 56-day 108 PFU group versus the 28-day 107 PFU group (p=0·0003). MVA-MERS-S was safe and immunogenic in individuals with previous and concurrent SARS-CoV-2 exposure. The second vaccination with the 108 PFU dose of MVA-MERS-S elicited a stronger humoral immune response when administered 56 days after the first dose than a 28-day interval. Further studies are needed to verify these findings in groups at risk for MERS-CoV exposure, and at risk of severe disease, including older individuals and those with relevant comorbidities. Coalition for Epidemic Preparedness Innovations, the German Centre for Infection Research, and the German Research Foundation.

Modelling П-Shaped Concentrating Optics for Lcpv Solar Cells Using Fresnel Lens

Abstract Most concentrating optics do not show good performance at higher incidence angles and have low acceptance angles and, therefore, they require a high-accuracy solar tracking system, which is costly. In this study, by detailed investigation of optics of the proposed П-shaped concentrating optics, it was found that system remained high in terms of optical efficiency and its concentration ratio at certain higher incidence angles. During the work, ray path through the concentrating optics, width of the light spot at different incidence angles were calculated. Optical efficiency, geometrical concentration ratio, concentration ratio at different incidence angles were found by the results of COMSOL Multiphysics calculations. It was found that the system had a high optical efficiency of approximately 95% and its concentration ratio of 3x-5x was at the range of ±0-20 degrees of incidence angle, and it could reduce the work of a solar tracking system. As well, an increase in the optical efficiency could be seen from 0 to 5 degrees of the incidence angle and an increase in the concentration ratio could be seen from 0 to 12 degrees of the incidence angle in terms of the reflective mirrors which helped redirect the rays to the solar cells. Optical systems with such a high incidence angle could reduce the performance of the solar tracker system, and it reduced the overall cost and energy consumption of the LCPV.

Single elemental planar light concentrator using skewed V-groove optics

Light concentrators are widely used to address the challenges of solar radiation's limited energy density. However, traditional light concentrators suffer from bulkiness, higher focal length, low solar acceptance, and cost factor due to the usage of large imaging optics elements. Waveguide-based planar light concentrators (PLC) have been engineered as a solution to these challenges. They work by collecting light at the incident face and channeling it to the lateral face of the waveguides. However, the existing PLC designs mostly consist of multiple optics elements, resulting in the need for precise positioning and point-to-point solar tracking. Addressing these complexities, a new design for waveguide-based PLC is presented. It features a simplified array of skewed V-grooves within an optical slab, essentially creating a single elemental optics. This novel skewed V-groove-based PLC (SV-PLC) introduces a low-concentration (i.e., <10X geometric concentration (GC)) solution that offers high angular acceptance along one axis. The current study aims to establish the novel design concept, validate, optimize, and assess the design through the Ray-tracing simulation. Further, based on the simulation results, a functional prototype was successfully fabricated in PMMA using laser machining. The results of the optical characterization of the SV-PLC showed that the Optical Efficiency (OE) was approximately around half the theoretical OE. Angular-dependent ray trace results showed a lower OE drop (<10 %) for incident angles less than 15°, and a maximum drop of 30 % (for a 10X GC design) for an incident angle of 23.5° (i.e., half the angle shift of the sun through seasons).

Thorough QT/QTc study to evaluate the effect of a single supratherapeutic dose of islatravir on QTc interval prolongation in healthy adults.

Islatravir is a deoxynucleoside analog being developed for the treatment of HIV-1 infection. Clinical studies are being conducted to evaluate islatravir, administered in combination with other antiretroviral therapies, at doses of 0.25 mg once daily and 2 mg once weekly. In multiple previous clinical studies, islatravir was generally well tolerated, with no clear trend in cardiac adverse events. A trial was conducted to evaluate the effect of islatravir on cardiac repolarization. A randomized, double-blind, active- and placebo-controlled phase 1 trial was conducted, in which a single dose of islatravir 0.75 mg, islatravir 240 mg (supratherapeutic dose), moxifloxacin 400 mg (active control), or placebo was administered. Continuous 12-lead electrocardiogram monitoring was performed before dosing through 24 hours after dosing. QT interval measurements were collected, and safety and pharmacokinetics were evaluated. Sixty-three participants were enrolled, and 59 completed the study. Fridericia's QT correction for heart rate was inadequate; therefore, a population-specific correction was applied (QTcP). The placebo-corrected change from baseline in QTcP (ΔΔQTcP) interval at the observed geometric mean maximum plasma concentration associated with islatravir 0.75 mg and islatravir 240 mg was <10 ms at all time points. Assay sensitivity was confirmed because the use of moxifloxacin 400 mg led to a ΔΔQTcP >10 ms. The pharmacokinetic profile of islatravir was consistent with that of previous studies, and islatravir was generally well tolerated. Results from the current trial suggest that single doses of islatravir as high as 240 mg do not lead to QTc interval prolongation.

Antibody Response to Symptomatic Infection With SARS-CoV-2 Omicron Variant Viruses, December 2021-June 2022.

We describe humoral immune responses in 105 ambulatory patients with laboratory-confirmed SARS-CoV-2 Omicron variant infection. In dried blood spot (DBS) collected within 5 days of illness onset and during convalescence, we measured binding antibody (bAb) against ancestral spike protein receptor binding domain (RBD) and nucleocapsid (N) protein using a commercial multiplex bead assay. Geometric mean bAb concentrations against RBD increased by a factor of 2.5 from 1258 to 3189 units/mL and by a factor of 47 against N protein from 5.5 to 259 units/mL between acute illness and convalescence; lower concentrations were associated with greater geometric mean ratios. Paired DBS specimens may be used to evaluate humoral response to SARS-CoV-2 infection.

Determinants of Systemic SARS-CoV-2-Specific Antibody Responses to Infection and to Vaccination: A Secondary Analysis of Randomised Controlled Trial Data.

SARS-CoV-2 infections elicit antibodies against the viral spike (S) and nucleocapsid (N) proteins; COVID-19 vaccines against the S-protein only. The BCG-Corona trial, initiated in March 2020 in SARS-CoV-2-naïve Dutch healthcare workers, captured several epidemic peaks and the introduction of COVID-19 vaccines during the one-year follow-up. We assessed determinants of systemic anti-S1 and anti-N immunoglobulin type G (IgG) responses using trial data. Participants were randomised to BCG or placebo vaccination, reported daily symptoms, SARS-CoV-2 test results, and COVID-19 vaccinations, and donated blood for SARS-CoV-2 serology at two time points. In the 970 participants, anti-S1 geometric mean antibody concentrations (GMCs) were much higher than anti-N GMCs. Anti-S1 GMCs significantly increased with increasing number of immune events (SARS-CoV-2 infection or COVID-19 vaccination): 104.7 international units (IU)/mL, 955.0 IU/mL, and 2290.9 IU/mL for one, two, and three immune events, respectively (p < 0.001). In adjusted multivariable linear regression models, anti-S1 and anti-N log10 concentrations were significantly associated with infection severity, and anti-S1 log10 concentration with COVID-19 vaccine type/dose. In univariable models, anti-N log10 concentration was also significantly associated with acute infection duration, and severity and duration of individual symptoms. Antibody concentrations were not associated with long COVID or long-term loss of smell/taste.

On Defect Evolution in EBM Additively Manufactured Ti-6Al-4V via In Situ Investigations.

This study concerned the in situ investigation of the defect evolution and fracture mechanism of additively manufactured (AM) Ti-6Al-4V under uniaxial tensile tests. In order to achieve this, microstructure characterization was initially carried out in order to identify the defects within the matrix of the candidate material. In situ testing was then performed, focusing on the spherical defect to observe its evolution under tensile loading. It was found that, before the fracture stage, the geometric evolution of the spherical defect towards an ellipse shape was dominated by the load in the tensile direction. In addition, the slip band density was found to be aggravated near the spherical defect due to the geometric discontinuity-induced stress concentration. During the fracture process, the defect geometry evolved as an irregular shape, which was mainly attributed to the micro-void-induced localized multi-axial stress state. The fracture analysis indicated that defects play a key role in crack initiation, leading to the fracture of LPBF materials.

Developmentand validation of carbodiimide-activated ELISA plate for quantifying IgG levels against Streptococcus pneumoniae capsular polysaccharides.

Background:Conventional microtiter plates lack the surface strength needed for effective binding of pneumococcalpolysaccharide antigens. This study tackles the limitation by altering the surface of polystyrene plates through carbodiimide activation under acidic pH conditions.Method:The microtiter plates were activated with carbodiimide coupling agents, N,N'-Dicyclohexylcarbodiimide (DCC) and N-Hydroxysuccinimide (NHS). They were subsequently coated with 13 pneumococcal antigens at a concentration of 5 μg/ml with a pH of 3.5. The IgG antibody titer was assessed utilizing the World Health Organization (WHO) ELISA protocol for 30 human serum samples. In addition, validation experiments were conducted to evaluate specificity and precision.Results: The modified plates exhibited two-times higher antibody titers compared to conventional plates across all 13 serotypes. Observations revealed elevated antibody levels, with geometric concentrations ranging between 0.96 μg/ml and 4.24 μg/ml.Conclusion:Carbodiimide activation and acidic pH modification of microtiter plates enhance sensitivity and specificity in detecting pneumococcal antibodies, critical for vaccination planning and immunity assessment.

Cassegrain-based concentrator with a high uniformity and acceptance angle

In this study, we improved a Cassegrain concentrator [Appl. Opt. 59, 8603 [2020)APOPAI0003-693510.1364/AO.400756] by redesigning the secondary optical element (SOE) with a freeform design, including geometrically mapped and tilted steps, to replace the design of the primary optical element (POE). This modification increased the acceptance angle and formed a more uniform irradiance distribution in the system without a homogenizer while maintaining the same level of efficiency. The result is a 1236× geometric concentration ratio, 1035× concentration ratio, 83.73% optical efficiency, ±0.40∘ acceptance angle, 8.96 uniformity, and 0.254 aspect ratio.

In Vitro Activitiy of Rezafungin in Comparison with Anidulafungin and Caspofungin against Invasive Fungal Isolates (2017 to 2022) in China.

The efficacy of different echinocandins is assessed by evaluating the in vitro activity of a novel antifungal, rezafungin, against invasive fungal isolates in comparison with anidulafungin and caspofungin. Using the broth microdilution (BMD) method, the susceptibility of 1000 clinical Candida isolates (including 400 C. albicans, 200 C. glabrata, 200 C. parapsilosis, 150 C. tropicalis and 50 C. krusei) and 150 Aspergillus isolates (100 A. fumigatus and 50 A. flavus) from the Eastern China Invasive Fungi Infection Group (ECIFIG) was tested for the antifungals including anidulafungin, rezafungin, caspofungin and fluconazole. The echinocandins showed strong activity against C. albicans that was maintained against fluconazole-resistant isolates. The GM MIC (geometric mean minimum inhibitory concentration) value of rezafungin was found to be comparable to that of anidulafungin or caspofungin against the five tested common Candida species. C. tropicalis exhibited higher resistance rates (about 8.67-40.67% in different antifungals) than the other four Candida species. Through the sequencing of FKS genes, we searched for mutations in echinocandin-resistant C. tropicalis isolates and found that all displayed alterations in FKS1 S654P. The determined MEC (minimal effective concentration) values against A. fumigatus and A. flavus for rezafungin (0.116 μg/mL, 0.110 μg/mL) are comparable to those of caspofungin (0.122 μg/mL, 0.142 μg/mL) but higher than for anidulafungin (0.064 μg/mL, 0.059 μg/mL). Thus, the in vitro activity of rezafungin appears comparable to anidulafungin and caspofungin against most common Candida and Aspergillus species. Rezafungin showed higher susceptibility rates against C. glabrata. Rezafungin indicates its potent activity for potential clinical application.

Response of selected nutrient elements in leaf tissues of sweet potato cv. 'Bophelo' to Nemafric-BL phytonematicide

Nemafric-BL phytonematicide is a potent plant-based nematicide which consistently suppress nematode population densities of root-knot (Meloidogyne species) nematodes on various crops, but with limited information on its effects on foliar nutrient elements in sweet potato. The objective of this study, therefore, was to investigate the effects of Nemafric-BL phytonematicide on accumulation of nutrient elements in leaf tissues of sweet potato cv. 'Bophelo' under greenhouse conditions in Limpopo Province, South Africa, during autumn (February-April) in 2021 and validated in 2022. The product was applied weekly at geometric concentrations, with mature leaves collected and prepared for analysis of nutrient elements at eight weeks. Seasonal interactions were not significant and therefore data were pooled (n = 70) and then subjected to the Curve-fitting Allelochemical Response Dose (CARD) algorithm computer model. Iron (R2 = 0.86), K (0.91) and Na (0.82) versus Nemafric-BL phytonematicide each exhibited negative quadratic relations, whereas Zn (0.83) versus the product exhibited positive quadratic relations. In all test elements, the CARD-generated biological indices illustrated that the accumulation of elements was highly sensitive to the concentration of Nemafric-BL phytonematicide. In conclusion, in sweet potato production, the application of Nemafric-BL phytonematicide can inhibit (Fe, K) and stimulate (Zn) the accumulation of certain elements in leaf tissues of sweet potato cv. ′Bophelo‵.

Associations of tubal ligation and hysterectomy with serum androgen and estrogen metabolites among postmenopausal women in the Women's Health Initiative Observational Study.

Hysterectomy is associated with subsequent changes in circulating hormone levels, but the evidence of an association for tubal ligation is unclear. We evaluated whether circulating concentrations of androgens and estrogens differ by tubal ligation or hysterectomy status in postmenopausal women from the Women's Health Initiative (WHI)-Observational Study (OS). Serum androgens and estrogens were measured in 920 postmenopausal women who did not use menopausal hormone therapy at the time of blood draw, of whom 139 self-reported a history of tubal ligation and 102 reported hysterectomy (with intact ovaries). Geometric mean hormone concentrations (GMs) and 95% confidence intervals (CIs) associated with a history of tubal ligation or hysterectomy (ever/never), as well as time since procedures, were estimated using adjusted linear regression with inverse probability of sampling weights to account for selection. Circulating levels of 12 androgen/androgen metabolites and 20 estrogen/estrogen metabolites did not differ by tubal ligation status. Among women reporting prior hysterectomy compared to women without hysterectomy, we observed lower levels of several androgens (e.g., testosterone (nmol/L): GMyes 0.46 [95% CI:0.37-0.57] vs. GMno 0.62 [95% CI:0.53-0.72]) and higher levels of estrogen metabolites, for example, 2-hydroxyestrone-3-methyl ether (GMyes 11.1 [95% CI:8.95-13.9] pmol/L vs. GMno 8.70 [95% CI:7.38-10.3]) and 4-methoxyestrone (GMyes 6.50 [95% CI:5.05-8.37] vs. GMno 4.92 [95% CI:4.00-6.05]). While we did not observe associations between prior tubal ligation and postmenopausal circulating hormone levels, our findings support that prior hysterectomy was associated with lower circulating testosterone levels and higher levels of some estrogen metabolites, which may have implications for future hormone-related disease risks.

Overall performance evaluation of a novel optical truncation method for compound parabolic concentrated photovoltaic-thermal system

A variable geometric concentration ratio (VGCR) truncation method was proposed to enhance the performance of compound parabolic concentrated photovoltaic-thermal (CPC-PVT) system in this study. Based on a multi-physics field model of optical-thermal-electrical coupling, numerical investigations using Monte Carlo ray tracing (MCRT) and finite volume method (FVM) were conducted to analyze the effects of the variation rate of truncation ratio (k) and light incident angle (θin) on the overall performance (optical efficiency (ηop), instantaneous thermal efficiency (ηth), instantaneous electrical efficiency (ηele,total), instantaneous electrical power (P), instantaneous exergy efficiency (ηu,total) and economic performance) of CPC-PVT system. Also, the overall performance between the VGCR-CPC-PVT system and the full CPC-PVT (FCPC-PVT) system was compared. The results indicate that, when θin is smaller, there is little disparity in the overall performance between the two systems. However, as k increases, ηop, ηele,total, ηth and ηu,total of VGCR-CPC-PVT system monotonically increase, and the area of the high-temperature region on the PV panel surface decreases. When θin is larger, the VGCR-CPC-PVT system has a smaller shaded area, ηop, ηele,total, P and ηu,total are significantly improved compared with the FCPC-PVT system. Additionally, k has a significant impact on the overall performance of the system, and P, ηu,total and saved reflective surface area (S) are the criteria for selecting k. When using P and ηu,total as the selection criteria, the optimal k value is 0.04. For 0°≤θin≤38°, the average ηop, average ηele,total, average ηth, average P and average ηu,total of the VGCR-CPC-PVT system with k = 0.04 are relatively improved by 1.91 %, 4.59 %, 2.42 %, 3.12 % and 4.04 %, respectively, while the reflector area decreases by 17.5 %, compared with the FCPC-PVT system. The cost-effectiveness of concentrator increases significantly with k.

Environmental phenol exposures in 6- to 12-week-old infants: The Infant Feeding and Early Development (IFED) study

BackgroundExposure to phenols, endocrine-disrupting chemicals used in personal care and consumer products, is widespread. Data on infant exposures are limited despite heightened sensitivity to endocrine disruption during this developmental period. We aimed to describe distributions and predictors of urinary phenol concentrations among U.S. infants ages 6–12 weeks. MethodsThe Infant Feeding and Early Development (IFED) study is a prospective cohort study of healthy term infants enrolled during 2010–2013 in the Philadelphia region. We measured concentrations of seven phenols in 352 urine samples collected during the 6- or 8- and/or 12-week study visits from 199 infants. We used linear mixed models to estimate associations of maternal, sociodemographic, infant, and sample characteristics with natural-log transformed, creatinine-standardized phenol concentrations and present results as mean percent change from the reference level. ResultsMedian concentrations (μg/L) were 311 for methylparaben, 10.3 for propylparaben, 3.6 for benzophenone-3, 2.1 for triclosan, 1.0 for 2,5-dichlorophenol, 0.7 for BPA, and 0.3 for 2,4-dichlorophenol. Geometric mean methylparaben concentrations were approximately 10 times higher than published estimates for U.S. children ages 3–5 and 6–11 years, while propylparaben concentrations were 3–4 times higher. Infants of Black mothers had higher concentrations of BPA (83%), methylparaben (121%), propylparaben (218%), and 2,5-dichorophenol (287%) and lower concentrations of benzophenone-3 (−77%) and triclosan (−53%) than infants of White mothers. Triclosan concentrations were higher in breastfed infants (176%) and lower in infants whose mothers had a high school education or less (−62%). Phenol concentrations were generally higher in summer samples. ConclusionsWidespread exposure to select environmental phenols among this cohort of healthy U.S. infants, including much higher paraben concentrations compared to those reported for U.S. children, supports the importance of expanding population-based biomonitoring programs to infants and toddlers. Future investigation of exposure sources is warranted to identify opportunities to minimize exposures during these sensitive periods of development.

Safety and Immunogenicity of an Accelerated Ebola Vaccination Schedule in People with and without Human Immunodeficiency Virus: A Randomized Clinical Trial.

The safety and immunogenicity of the two-dose Ebola vaccine regimen MVA-BN-Filo, Ad26.ZEBOV, 14 days apart, was evaluated in people without HIV (PWOH) and living with HIV (PLWH). In this observer-blind, placebo-controlled, phase 2 trial, healthy adults were randomized (4:1) to receive MVA-BN-Filo (dose 1) and Ad26.ZEBOV (dose 2), or two doses of saline/placebo, administered intramuscularly 14 days apart. The primary endpoints were safety (adverse events (AEs)) and immunogenicity (Ebola virus (EBOV) glycoprotein-specific binding antibody responses). Among 75 participants (n = 50 PWOH; n = 25 PLWH), 37% were female, the mean age was 44 years, and 56% were Black/African American. AEs were generally mild/moderate, with no vaccine-related serious AEs. At 21 days post-dose 2, EBOV glycoprotein-specific binding antibody responder rates were 100% among PWOH and 95% among PLWH; geometric mean antibody concentrations were 6286 EU/mL (n = 36) and 2005 EU/mL (n = 19), respectively. A total of 45 neutralizing and other functional antibody responses were frequently observed. Ebola-specific CD4+ and CD8+ T-cell responses were polyfunctional and durable to at least 12 months post-dose 2. The regimen was well tolerated and generated robust, durable immune responses in PWOH and PLWH. Findings support continued evaluation of accelerated vaccine schedules for rapid deployment in populations at immediate risk. Trial registration: NCT02598388 (submitted 14 November 2015).