This article provides a database of the mechanical properties of additively manufactured polymeric materials fabricated using material extrusion (e.g., fused filament fabrication (FFF)). Mechanical ...properties available in the literatures are consolidated in table form for different polymeric materials for FFF. Mechanical properties such as tensile, compressive, flexural, interlayer, fatigue, and creep properties are discussed in detail. The effects of printing parameters such as raster angle, infill, and specimen orientation on properties are also provided, together with a discussion of the possible causes (e.g., texture, microstructure changes, and defects) of anisotropy in properties. In addition to that, research gaps are identified which warrant further investigation.
Particle trapping and binding in optical potential wells provide a versatile platform for various biomedical applications. However, implementation systems to study multi-particle contact interactions ...in an optical lattice remain rare. By configuring an optofluidic lattice, we demonstrate the precise control of particle interactions and functions such as controlling aggregation and multi-hopping. The mean residence time of a single particle is found considerably reduced from 7 s, as predicted by Kramer's theory, to 0.6 s, owing to the mechanical interactions among aggregated particles. The optofluidic lattice also enables single-bacteria-level screening of biological binding agents such as antibodies through particle-enabled bacteria hopping. The binding efficiency of antibodies could be determined directly, selectively, quantitatively and efficiently. This work enriches the fundamental mechanisms of particle kinetics and offers new possibilities for probing and utilising unprecedented biomolecule interactions at single-bacteria level.
Consumption of fruit and vegetables is associated with a decreased risk of heart disease and cancer. This has been ascribed in part to antioxidants in these foods inactivating reactive oxygen species ...involved in initiation or progression of these diseases. Non-nutritive anthocyanins are present in significant amounts in the human diet. However, it is unclear whether they have health benefits in humans.
To determine whether daily consumption of anthocyanin-rich cranberry juice could alter plasma antioxidant activity and biomarkers of oxidative stress.
20 healthy female volunteers aged 18-40 y were recruited. Subjects consumed 750 ml/day of either cranberry juice or a placebo drink for 2 weeks. Fasted blood and urine samples were obtained over 4 weeks. The total phenol, anthocyanin and catechin content of the supplements and plasma were measured. Anthocyanin glycosides were identified by tandem mass spectrometry (MS-MS). Vitamin C, homocysteine (tHcy) and reduced glutathione (GSH) were measured by HPLC. Total antioxidant ability was determined using electron spin resonance (ESR) spectrometry and by the FRAP assay. Plasma total cholesterol, high density lipoprotein (HDL), and low density lipoprotein (LDL) cholesterol and triglycerides (TG) were measured. Glutathione peroxidase (GSH-Px), catalase (CAT) and superoxide dismutase (SOD) activities were measured in erythrocytes. Urine was collected for analysis of malondialdehyde (MDA) by HPLC and 8-oxo-deoxyguanosine (8-oxo-dG) by ELISA. Endogenous and induced DNA damage were measured by single cell gel electrophoresis (SCGE) in lymphocytes.
Vitamin C, total phenol, anthocyanin and catechin concentrations and FRAP and ESR values were significantly higher in the cranberry juice compared with the placebo. Cyanidin and peonidin glycosides comprised the major anthocyanin metabolites peonidin galactoside (29.2%) > cyanidin arabinoside (26.1%) > cyanidin galactoside (21.7%) > peonidin arabinoside (17.5%) > peonidin glucoside (4.1%) > cyanidin glucoside (1.4 %). Plasma vitamin C increased significantly (P<0.01) in volunteers consuming cranberry juice. No anthocyanins (plasma) or catechins (plasma or urine) were detectable and plasma total phenols, tHcy,TC,TG,HDL and LDL were unchanged. The antioxidant potential of the plasma, GSH-Px, CAT and SOD activities, and MDA were similar for both groups. Supplementation with cranberry juice did not affect 8-oxo-deoxyguanosine in urine or endogenous or H(2)O(2)-induced DNA damage in lymphocytes.
Cranberry juice consumption did not alter blood or cellular antioxidant status or several biomarkers of lipid status pertinent to heart disease. Similarly, cranberry juice had no effect on basal or induced oxidative DNA damage. These results show the importance of distinguishing between the in vitro and in vivo antioxidant activities of dietary anthocyanins in relation to human health.
Characterising the Pelletron beam at the University of Melbourne Steinberg, A.F.; Yap, J.S.L.; Norman, H.X.Q. ...
Nuclear instruments & methods in physics research. Section A, Accelerators, spectrometers, detectors and associated equipment,
02/2024, Volume:
1059
Journal Article
Abstract
STUDY QUESTION
Are higher overall and central adiposity associated with reduced fecundability, measured by time-to-pregnancy (TTP), in Asian women?
SUMMARY ANSWER
Higher overall adiposity, ...but not central adiposity, was associated with longer TTP in Asian women.
WHAT IS KNOWN ALREADY
High body mass index (BMI) has been associated with a longer TTP, although the associations of body composition and distribution with TTP are less clear. There are no previous studies of TTP in Asian women, who have a relatively higher percentage of body fat and abdominal fat at relatively lower BMI.
STUDY DESIGN, SIZE, DURATION
Prospective preconception cohort using data from 477 Asian (Chinese, Malay and Indian) women who were planning to conceive and enrolled in the Singapore PREconception Study of long-Term maternal and child Outcomes (S-PRESTO) study, 2015-2017.
PARTICIPANTS/MATERIALS, SETTING, METHODS
Women's mean age was 30.7 years. Overall adiposity was assessed by BMI, sum of 4-site skinfold thicknesses (SFT) and total body fat percentage (TBF%, measured using air displacement plethysmography); central adiposity was assessed by waist circumference (WC), waist-to-hip ratio (WHR), waist-to-height ratio (WHtR) and A body Shape Index (ABSI). Pregnancy occurring within one year from recruitment was ascertained by ultrasonography. Those who did not conceive within one year of recruitment, were lost to follow-up, or initiated fertility treatment were censored. TTP was measured in cycles. Discrete-time proportional hazards models were used to estimate the fecundability ratio (FR) and 95% confidence interval (CI) for each anthropometric measure in association with fecundability, adjusting for confounders.
MAIN RESULTS AND THE ROLE OF CHANCE
Compared to women with a normal BMI of 18.5-22.9 kg/m2, women with higher BMI of 23-27.4 and ≥27.5 kg/m2 showed lower FR of 0.66 (95% CI 0.45, 0.97) and 0.53 (0.31, 0.89), respectively. Compared to women in the lowest quartile of SFT (25-52.9 mm), those in the highest quartile of ≥90.1 mm showed lower FR of 0.58 (95% CI 0.36, 0.95). Compared to women in the lowest quartile of TBF% (13.6-27.2%), those in the upper two quartiles of 33.0-39.7% and ≥39.8% showed lower FR of 0.56 (95% CI 0.32, 0.98) and 0.43 (0.24, 0.80), respectively. Association of high BMI with reduced fecundability was particularly evident among nulliparous women. Measures of central adiposity (WC, WHR, WHtR, ABSI) were not associated with fecundability.
LIMITATIONS REASONS FOR CAUTION
Small sample size could restrict power of analysis.The analysis was confined to planned pregnancies, which could limit generalizability of findings to non-planned pregnancies, estimated at around 44% in Singapore. Information on the date of last menstrual period for each month was not available, hence the accuracy of self-reported menstrual cycle length could not be validated, potentially introducing error into TTP estimation. Measures of exposures and covariates such as cycle length were not performed repeatedly over time; cycle length might have changed during the period before getting pregnant.
WIDER IMPLICATIONS OF THE FINDINGS
Other than using BMI as the surrogate measure of body fat, we provide additional evidence showing that higher amounts of subcutaneous fat that based on the measure of SFT at the sites of biceps, triceps, suprailiac and subscapular, and TBF% are associated with longer TTP. Achieving optimal weight and reducing total percentage body fat may be a potential intervention target to improve female fertility. The null results observed between central adiposity and TTP requires confirmation in further studies.
STUDY FUNDING/COMPETING INTEREST(S)
This research is supported by Singapore National Research Foundation under its Translational and Clinical Research Flagship Programme and administered by the Singapore Ministry of Health's National Medical Research Council, (NMRC/TCR/004-NUS/2008; NMRC/TCR/012-NUHS/2014). Additional funding is provided by the Singapore Institute for Clinical Sciences, Agency for Science Technology and Research (A*STAR), Singapore. Y.S.C., K.M.G., F.Y. and Y.S.L. have received reimbursement to speak at conferences sponsored by companies selling nutritional products. Y.S.C., K.M.G. and S.Y.C. are part of an academic consortium that has received research funding from Abbott, Nutrition, Nestle and Danone. Other authors declared no conflicts of interest.
TRIAL REGISTRATION NUMBER
N/A.
Extant research has demonstrated that parenting behaviour can be a significant contributor to the development of brain structure and mental health during adolescence. Nonetheless, there is limited ...research examining these relationships during late childhood, and particularly in the critical period of brain development occurring between 8 and 10 years of age. The effects of the family environment on the brain during late childhood may have significant implications for later functioning, and particularly mental health. The Families and Childhood Transitions Study (FACTS) is a multidisciplinary longitudinal cohort study of brain development and mental health, with two waves of data collection currently funded, occurring 18-months apart, when child participants are aged approximately 8- and 10-years old.
Participants are 163 children (M age SD = 8.44 0.34 years, 76 males) and their mothers (M age SD = 40.34 5.43 years). Of the 163 families who consented to participate, 156 completed a video-recorded and observer-coded dyadic interaction task and 153 completed a child magnetic resonance imaging brain scan at baseline. Families were recruited from lower socioeconomic status (SES) areas to maximise rates of social disadvantage and variation in parenting behaviours. All experimental measures and tasks completed at baseline are repeated at an 18-month follow-up, excluding the observer coded family interaction tasks. The baseline assessment was completed in October 2015, and the 18-month follow up will be completed May 2017.
This study, by examining the neurobiological and mental health consequences of variations in parenting, has the potential to significantly advance our understanding of child development and risk processes. Recruitment of lower SES families will also allow assessment of resilience factors given the poorer outcomes often associated with this population.
Tamoxifen is the standard-of-care treatment for estrogen receptor-positive premenopausal breast cancer. We examined tamoxifen metabolism via blood metabolite concentrations and germline variations of ...CYP3A5, CYP2C9, CYP2C19 and CYP2D6 in 587 premenopausal patients (Asians, Middle Eastern Arabs, Caucasian-UK; median age 39 years) and clinical outcome in 306 patients. N-desmethyltamoxifen (DM-Tam)/(Z)-endoxifen and CYP2D6 phenotype significantly correlated across ethnicities (R(2): 53%, P<10(-77)). CYP2C19 and CYP2C9 correlated with norendoxifen and (Z)-4-hydroxytamoxifen concentrations, respectively (P<0.001). DM-Tam was influenced by body mass index (P<0.001). Improved distant relapse-free survival (DRFS) was associated with decreasing DM-Tam/(Z)-endoxifen (P=0.036) and increasing CYP2D6 activity score (hazard ratio (HR)=0.62; 95% confidence interval (CI), 0.43-0.91; P=0.013). Low (<14 nM) compared with high (>35 nM) endoxifen concentrations were associated with shorter DRFS (univariate P=0.03; multivariate HR=1.94; 95% CI, 1.04-4.14; P=0.064). Our data indicate that endoxifen formation in premenopausal women depends on CYP2D6 irrespective of ethnicity. Low endoxifen concentration/formation and decreased CYP2D6 activity predict shorter DRFS.
WHAT IS ALREADY KNOWN ABOUT THIS SUBJECT
• Tamoxifen is metabolized to active metabolites, 4‐hydroxytamoxifen and endoxifen, by multiple cytochrome P450 (CYP) enzymes including CYP2D6, CYP3A4/5, ...CYP2C9/19, CYP1A2 and CYP2B6.
• The steady‐state plasma concentrations of tamoxifen and its metabolites can be affected by variations in the activity of these enzymes.
• Although CYP2D6*4 and *10 have been shown to influence the plasma concentration of endoxifen in Caucasian and Korean patients respectively, there is still a paucity of data on CYP2D6 pharmacogenetics in other Orientals such as Chinese, Malays and Indians.
WHAT THIS STUDY ADDS
• Pharmacogenetic analyses of a comprehensive panel of CYP2D6 polymorphisms (*2, *2A, *3, *4, *5, *6, *7, *8, *9, *10, *12, *14, *17, *29, *41 and *xN) were performed in three distinct Asian ethnic groups and breast cancer patients with CYP2D6*5 and *10 found to be highly prevalent.
• Both CYP2D6*5 and *10 were significantly associated with lower endoxifen and higher N‐desmethyltamoxifen concentrations as well as a lower rate of metabolic conversion of N‐desmethyltamoxifen to endoxifen.
• Polymorphisms present in CYP3A5, CYP2C9 and CYP2C19 were not found to be significantly associated with plasma concentrations of analytes suggesting that these enzymes may be playing minor roles in the metabolic pathway of tamoxifen compared with CYP2D6.
AIM To investigate the impact of genetic polymorphisms in CYP2D6, CYP3A5, CYP2C9 and CYP2C19 on the pharmacokinetics of tamoxifen and its metabolites in Asian breast cancer patients.
METHODS A total of 165 Asian breast cancer patients receiving 20 mg tamoxifen daily and 228 healthy Asian subjects (Chinese, Malay and Indian; n= 76 each) were recruited. The steady‐state plasma concentrations of tamoxifen and its metabolites were quantified using high‐performance liquid chromatography. The CYP2D6 polymorphisms were genotyped using the INFINITI™ CYP450 2D6I assay, while the polymorphisms in CYP3A5, CYP2C9 and CYP2C19 were determined via direct sequencing.
RESULTS The polymorphisms, CYP2D6*5 and *10, were significantly associated with lower endoxifen and higher N‐desmethyltamoxifen (NDM) concentrations. Patients who were *1/*1 carriers exhibited 2.4‐ to 2.6‐fold higher endoxifen concentrations and 1.9‐ to 2.1‐fold lower NDM concentrations than either *10/*10 or *5/*10 carriers (P < 0.001). Similarly, the endoxifen concentrations were found to be 1.8‐ to 2.6‐times higher in *1/*5 or *1/*10 carriers compared with *10/*10 and *5/*10 carriers (P≤ 0.001). Similar relationships were observed between the CYP2D6 polymorphisms and metabolic ratios of tamoxifen and its metabolites. No significant associations were observed with regards to the polymorphisms in CYP3A5, CYP2C9 and CYP2C19.
CONCLUSIONS The present study in Asian breast cancer patients showed that CYP2D6*5/*10 and *10/*10 genotypes are associated with significantly lower concentrations of the active metabolite of tamoxifen, endoxifen. Identifying such patients before the start of treatment may be useful in optimizing therapy with tamoxifen. The role of CYP3A5, CYP2C9 and CYP2C19 seem to be minor.
Abstract
TURBO – Technology for Ultra Rapid Beam Operation – is a novel beam delivery system (BDS) in development at the University of Melbourne. The BDS determines several aspects of treatment ...delivery where a key bottleneck is the deadtime associated with beam energy variation. Beamlines at treatment facilities have a ±1% momentum acceptance range, requiring all the magnetic fields to adjust to deliver different energy beams at multiple depths in the tumour volume. A BDS using Fixed Field Alternating Gradient (FFA) optics could reduce the energy layer switching time (ELST) by enabling the transport of a large range of beam energies within the same fixed fields. We present recent progress and ongoing developments with TURBO, a proof-of-concept demonstrator adapted for low energy protons. Characterisation measurements were performed to determine realistic parameters for beam transport and particle tracking modelling. Simulation and experimental studies are shown for an energy degrader. We mention considerations of canted-cosine-theta magnets and further work to explore the clinical feasibility of a scaled-up BDS for charged particle therapy.
Large energy acceptance arcs have been proposed for applications such as cancer therapy, muon accelerators, and recirculating linacs. The efficacy of hadron therapy can be improved by reducing the ...energy layer switching time, however this is currently limited by the small momentum acceptance of the beam delivery system ( < ± 1 % ). A “closed-dispersion arc” with a large momentum acceptance has the potential to remove this bottleneck, however such a beamline has not yet been constructed. We have developed a design methodology for large momentum acceptance arcs with Fixed Field Accelerator optics, applying it to a demonstrator beam delivery system for protons at 0.5–3.0 MeV ( ± 42 % momentum acceptance) as part of the Technology for Ultra-Rapid Beam Operation project at the University of Melbourne. Using realistic magnetic fields, a beamline has been designed with zero dispersion at either end. An algorithm has been devised for the construction of permanent magnet Halbach arrays for this beamline with multipole error below one part in 10 4 , using commercially available magnets. The sensitivity to errors has been investigated, finding that the delivered beam is robust in realistic conditions. This study demonstrates that a closed-dispersion arc with fixed fields can achieve a large momentum acceptance, and we outline future work required to develop these ideas into a complete proof-of-principle beam delivery system that can be scaled up for a medical facility. Published by the American Physical Society 2024
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