Decisional trade-offs towards doping and their association with moral attitudes and health risk perceptions: A mixed methods study.

The objective of the present research was to examine doping-related decisional trade-offs, and their relationship with health risk perceptions towards doping and moral attitudes in sport. A mixed methods sequential-explanatory design was used. In Study 1,249, Mixed Martial Arts (MMA) athletes from 16 countries completed anonymous online questionnaires on decisional trade-offs related to doping, health risk beliefs towards doping, moral attitudes in sport, and socio-demographic variables. The results showed that almost 1 in 10 athletes would trade their life for sporting success, independently of the moral implications of their choice. When mortal threat was absent, 31.5% of the athletes would trade morality for sporting success. Decisional trade-off choices differentiated scores in moral attitudes, such as acceptance of cheating and keeping winning in proportion. In Study 2, 11 British competitive MMA athletes were interviewed about decisional trade-offs involving moral violations or mortal threats. Thematic analysis corroborated the Study 1 findings, with most athletes dismissing the doping choice involving a mortal threat but endorsing the one where the mortal threat was absent. Anti-doping education in MMA athletes should target the decision-making process underlying doping, with an emphasis on moral values and the adverse health risk effects of doping.

Structure revision and chemical synthesis of ligandrol's main bishydroxylated long-term metabolic marker.

Although the main bishydroxylated long-term metabolite of the WADA-banned anabolic agent ligandrol (LGD-4033) is an important metabolic marker, it is not readily available in sufficient quantities to facilitate the development and validation of related analytical protocols or sensors. A chemically more robust structure was postulated as an alternative to the one previously established. The NMR spectra of the synthesized material and its LC-HRMS comparison with a relevant metabolic sample support the proposed structural revision.

Investigations into the elimination profiles and metabolite ratios of micro-dosed selective androgen receptor modulator LGD-4033 for doping control purposes.

LGD-4033 (ligandrol) is a selective androgen receptor modulator (SARM), which is prohibited in sports by the World Anti-Doping Agency (WADA) and led to 62 adverse analytical findings (AAFs) in 2019. But not only deliberate doping with LGD-4033 constitutes a problem. In the past years, some AAFs that concerned SARMs can be attributed to contaminated dietary supplements (DS). Thus, the urgency to develop methods to differentiate between inadvertent doping and abuse of SARMs to benefit from the performance-enhancing effect of the compound in sports is growing. To gain a better understanding of the metabolism and excretion patterns of LGD-4033, human micro-dose excretion studies at 1, 10, and 50 µg LGD-4033 were conducted. Collected urine samples were prepared for analysis using enzymatic hydrolysis followed by solid-phase extraction and analyzed via LC-HRMS/MS. Including isomers, a total of 15 phase I metabolites were detected in the urine samples. The LC-HRMS/MS method was validated for qualitative detection of LGD-4033, allowing for a limit of detection (LOD) of 8 pg/mL. The metabolite M1, representing the epimer of LGD-4033, was synthesized and the structure elucidated by NMR spectroscopy. As the M1/LGD-4033 ratio changes over time, the ratio and the approximate LGD-4033 concentration can contribute to estimating the time point of drug intake and dose of LGD-4033 in doping control urine samples, which is particularly relevant in anti-doping result management.

Determination of salmeterol, α-hydroxysalmeterol and fluticasone propionate in human urine and plasma for doping control using UHPLC-QTOF-MS.

Salmeterol and fluticasone are included in the Prohibited List annually issued by the World Anti-Doping Agency. While for other permitted beta-2 agonists a threshold has been established, above which any finding constitutes an Adverse Analytical Finding, this is not the case with salmeterol. The salmeterol metabolite, α-hydroxysalmeterol, has been described as a potentially more suitable biomarker for the misuse of inhaled salmeterol. In this study, a new and rapid UHPLC-QTOF-MS method was developed and validated for the simultaneous quantification of salmeterol, α-hydroxysalmeterol and fluticasone in human urine and plasma, which can be used for doping control. The analytes of interest were extracted by means of solid phase extraction and were separated on a Zorbax Eclipse Plus C18 column. Detection was performed in a quadrupole time-of-flight mass spectrometer equipped with an electrospray ionization source, in positive mode for the detection of salmeterol and its metabolite and in negative mode for the detection of fluticasone. Method was validated over a linear range from 0.10 to 2.00 ng/ml for salmeterol and fluticasone, and from 1.00 to 20.0 ng/ml for α-hydroxysalmeterol, in urine, whereas in plasma, the linear range was from 0.025 to 0.500 ng/ml for salmeterol and fluticasone, respectively.

Simultaneous quantitation and identification of intact Nandrolone phase II oxo-metabolites based on derivatization and inject LC-MS/(HRMS) methodology.

Α sensitive and selective derivatization and inject method for the quantification of intact nandrolone phase II oxo-metabolites was developed and validated using liquid chromatography - (tandem high resolution) mass spectrometry (LC-MS/(HRMS)). For the derivatization, Girard's reagent T (GRT) was used directly in natural urine samples and the analysis of the metabolites of interest was performed by direct injection into LC-MS/(HRMS) system operating in positive ionization mode. Derivatization enabled the efficient detection of nandrolone oxo-metabolites, while at the same time producing intense product ions under collision-induced dissociation (CID) conditions that are related to metabolites of the steroid backbone and not to the conjugated moieties. Glucuronide and sulfate metabolites of nandrolone were chromatographically resolved and quantified in the same run in the range of 1-100 ng mL-1, while at the same time structure identification could be performed for each metabolite. Full validation of the method was performed according to the World Anti-Doping Agency (WADA) International Standard for Laboratories (ISL). Nandrolone oxo-metabolites were quantified in two sets of urine samples, the first set consisted of real urine samples previously detected as negative and the second set consisted of urine samples collected from two excretion studies after nandrolone decanoate administration. The results for 19-norandrosterone glucuronide (19-NAG) and 19-noretiocholanolone glucuronide (19-NEG) were compared with those obtained by traditional gas chromatography - (tandem) mass spectrometry (GC-MS/[MS]) method.

CODD: A benchmark dataset for the automated sorting of construction and demolition waste.

This study presents the Construction and Demolition Waste Object Detection Dataset (CODD), a benchmark dataset specifically curated for the training of object detection models and the full-scale implementation of automated sorting of Construction and Demolition Waste (CDW). The CODD encompasses a comprehensive range of CDW scenarios, capturing a diverse array of debris and waste materials frequently encountered in real-world construction and demolition sites. A noteworthy feature of the presented study is the ongoing collaborative nature of the dataset, which invites contributions from the scientific community, ensuring its perpetual improvement and adaptability to emerging research and practical requirements. Building upon the benchmark dataset, an advanced object detection model based on the latest bounding box and instance segmentation YOLOV8 architecture is developed to establish a baseline performance for future comparisons. The CODD benchmark dataset, along with the baseline model, provides a reliable reference for comprehensive comparisons and objective assessments of future models, contributing to progressive advancements and collaborative research in the field.

Targeted Metabolic Investigation of Ligandrol and Analytical Methods Validation for Its Main Long-term Metabolite.

Prompted by the need for related analytical reference material in the frame of the fight against doping in sports, synthetic efforts towards the main long-term bishydroxylated metabolite (LGD-LTM1) of the nonsteroidal selective androgen receptor modulator (SARM) ligandrol have produced related derivatives that were exploited for a targeted metabolite analysis of urine samples obtained in the course of previous excretion studies of this SARM. Further clarifying ligandrol's metabolic profile, the availability of synthetic reference material permitted the structural elucidation of a previously reported pyrrolidinone-type metabolite and revealed its potential analytical utility as an additional long-term marker. Moreover, synthetic reference material enabled the comparison and validation of liquid chromatography coupled with mass spectrometry (LC-MS)-based and gas chromatography coupled with mass spectrometry (GC-MS)-based detection and identification methods focusing on the LGD-LTM1 marker.

Real-time construction demolition waste detection using state-of-the-art deep learning methods; single-stage vs two-stage detectors.

Central to the development of a successful waste sorting robot lies an accurate and fast object detection system. This study assesses the performance of the most representative deep-learning models for the real-time localisation and classification of Construction and Demolition Waste (CDW). For the investigation, both single-stage (SSD, YOLO) and two-stage (Faster-RCNN) detector architectures coupled with various backbone feature extractors (ResNet, MobileNetV2, efficientDet) were considered. A total of 18 models of variable depth were trained and tested on the first openly accessible CDW dataset developed by the authors of this study. This dataset consists of images of 6600 samples of CDW belonging to three object categories: brick, concrete, and tile. For an in-depth examination of the performance of the developed models under working conditions, two testing datasets containing normally and heavily stacked and adhered samples of CDW were developed. A comprehensive comparison between the different models yields that the latest version of the YOLO series (YoloV7) attains the best accuracy (mAP50:95 ≈ 70%) at the highest inference speed (<30 ms), while also exhibiting enough precision to deal with severely stacked and adhered samples of CDW. Additionally, it was observed that despite the rising popularity of single-stage detectors, apart from YoloV7, Faster-RCNN models remain the most robust in terms of exhibiting the least mAP fluctuations over the testing datasets considered.

Accurate and rapid identification of Candida spp. frequently associated with fungemia by using PCR and the microarray-based Prove-it Sepsis assay.

The rapid identification of microbes responsible for bloodstream infections (BSIs) allows more focused and effective therapies and outcomes. DNA sequence-based methods offer an opportunity for faster, accurate diagnosis and for effective therapy. As our objective of the study, the ability of the Prove-it Sepsis platform, already proven as a rapid PCR- and microarray-based assay for the majority of sepsis-causing bacteria, was extended to also rapidly identify clinically relevant yeasts in blood culture. The performance characteristics of this extended platform are described. We found that the extended diagnostic Prove-it Sepsis platform was found to be highly accurate when analyzing primary isolates, spiked blood cultures, nucleic acid extracts from a retrospective blood culture data set, and primary blood cultures. Comparison of the blood culture results from the Prove-it Sepsis platform with those from conventional culture-based methods or by gene sequencing demonstrated a sensitivity of 99% and a specificity of 98% for fungal targets (based on analysis of a total of 388 specimens). Total assay time was 3 h from DNA extraction to BSI diagnosis. These results extend the performance characteristics of the Prove-it platform for bacteria to the easy, rapid, and accurate detection and species identification of yeasts in positive blood cultures. Incorporation of this extended and rapid diagnostic platform into the tools for clinical patient management would allow possibly faster identification and more focused therapies for BSIs.

Incidence of dsRNA mycoviruses in a collection of Aspergillus fumigatus isolates.

A collection of clinical and environmental isolates of the opportunistic human pathogen, Aspergillus fumigatus, were screened for the presence of mycoviruses and 6.6 % of 366 isolates contained dsRNA segments ranging in size from ~1.0 to 4.0 kbp. The dsRNAs were categorised into three different groups comprising bipartite dsRNAs, quadripartite dsRNAs, representative isolates of which have both been sequenced, and an uncharacterised mycovirus, whose genome apparently consists of four dsRNAs 1-2.5 kbp in size. Here, we describe dsRNA incidence in the A. fumigatus isolates examined, their provenance and also note that on occasion individual isolates were infected with two groups of different dsRNAs.

Effect of Mechanically Treated Recycled Aggregates on the Long Term Mechanical Properties and Durability of Concrete.

The objective of this research was to study the effect of an optimal mechanical treatment method to reduce the mortar adhered on recycled aggregates (RCA) on the long-term mechanical properties and durability of concretes containing RCA at different replacement levels. It was found that concretes incorporating treated RCA exhibited sharper and more significant increase on 90- and 365-day compressive strengths than any other investigated mixture. The same mixtures also benefitted from a 'shrinkage-controlling' effect, where strains and mass losses were reduced by almost 15% and 10%, respectively, compared to the reference concrete. While sulfate resistance and carbonation resistance are predominantly defined by the hydration products available within the cement paste and not to a large extent by the aggregate type and quality, the incorporation of either treated or untreated RCA in concrete did not appear to expose RACs to significant durability threats.

Investigation of the Geopolymerization Potential of a Waste Silica-Rich Diabase Mud.

Diabase mud (DM) is a silica-rich residue yielding from aggregate crushing and washing operations in quarries. This work focuses on identifying the geopolymerization potential of a diabase mud through characterization of its mineralogical composition, investigation of its reactivity, and assessment of the early compressive strengths of alkali activated mixtures formulated based on the mud's dissolution results. The findings suggest that considerably low amounts of Al and Si metals were dissolved following the dissolution tests conducted on DM, however, the incorporation of small quantities of CEM I, gypsum, and metakaolin (MK) moderately at a Na2SiO3:NaOH ratio of 50:50 and with a molarity of NaOH of 4 M enhanced the geopolymerization compared to low L/S ratio mixtures cured at different conditions. When M was increasing, the high L/S ratio mixtures exhibited fluctuations in strengths, especially beyond a 10 M NaOH molarity. Maximum strengths of mixtures at equivalent molarity of 10 were achieved when the Na2SiO3:NaOH ratio reached 30:70, regardless of the ambient conditions and the presence of CEM I. The curing conditions, the ratio of Na2SO3:NaOH, and the presence of CEM I in the DM-based mixtures did not appear to significantly affect the mixture when NaOH concentration was between 2 M and 4 M; at higher molarities, however, these enhanced the strengths of the geopolymerized DM.

Development of a High Strength Geopolymer Incorporating Quarry Waste Diabase Mud (DM) and Ground Granulated Blast-Furnace Slag (GGBS).

This study presents the development and experimental assessment of novel, high strength, cementless binders that incorporate alkali-activated local waste. A silica-rich diabase mud (DM), currently considered as waste, was previously investigated for geopolymerization, signifying that the DM lacked the necessary reactivity to provide a stable geopolymer binder alone. Moreover, even after incorporation of small amounts of cement and metakaolin, the DM mixtures still did not yield adequate mechanical properties. In this study, the local DM was instead combined with another industrial byproduct known as Ground Granulated Blast-furnace Slag (GGBS) in varying mixtures. The mixture design trials enabled the development of three high strength cementless geopolymer mixtures with 28-day compressive strengths ranging between 60 and 100 MPa, comparable to conventional concrete compressive strengths. The results indicate that the innovative geopolymer material is very promising for the manufacturing of pavement tiles and other precast construction products. Most importantly, this study presents the first successful development of a construction material of adequate compressive strength that can absorb large quantities of the abundant quarry waste, following a course of 10 years of unsuccessful attempts to valorize the local DM. Although difficulties were encountered due to a high reactivity rate, especially for the mix that included the highest GGBS content, prototype pavement tiles were manufactured and assessed experimentally. The results reveal a promising potential of valorizing the local DM in the development of precast geopolymer products, despite the effects of shrinkage cracking on the experimental evaluation of the material mechanical properties.

The effects of dsRNA mycoviruses on growth and murine virulence of Aspergillus fumigatus.

Some isolates of the opportunistic human pathogenic fungus Aspergillus fumigatus are known to be infected with mycoviruses. The dsRNA genomes of two of these mycoviruses, which include a chrysovirus and a partitivirus, have been completely sequenced and an RT-PCR assay for the viruses has been developed. Through curing virus-infected A. fumigatus isolates by cycloheximide treatment and transfecting virus-free isolates with purified virus, as checked by RT-PCR, isogenic virus-free and virus-infected lines of the fungus were generated whose phenotypes and growth have been directly compared. Mycovirus infection of A. fumigatus with either the chrysovirus or the partitivirus resulted in significant aberrant phenotypic alterations and attenuation of growth of the fungus but had no effect on susceptibility to common antifungals. Chrysovirus infection of A. fumigatus caused no significant alterations to murine pathogenicity.

Determination of growth hormone releasing peptides (GHRP) and their major metabolites in human urine for doping controls by means of liquid chromatography mass spectrometry.

A family of small peptides has reached the focus of doping controls representing a comparably new strategy for cheating sportsmen. These growth hormone releasing peptides (GHRP) are orally active and induce an increased production of endogenous growth hormone (GH). While the established test for exogenous GH fails, the misuse of these prohibited substances remains unrecognized. The present study provides data for the efficient extraction of a variety of known drug candidates (GHRP-1, GHRP-2, GHRP-4, GHRP-5, GHRP-6, alexamorelin, ipamorelin, and hexarelin) from human urine with subsequent mass spectrometric detection after liquid chromatographic separation. The used method potentially enables the retrospective evaluation of the acquired data for unknown metabolites by means of a non-targeted approach with high-resolution/high-accuracy full-scan mass spectrometry with additional higher collision energy dissociation experiments. This is of great importance due to the currently unknown metabolism of most of the targets and, thus, the method is focused on the intact peptidic drugs. Only the already characterised major metabolite of GHRP-2 (D-Ala-D-2-naphthylAla-L-Ala, as well as its stable isotope-labelled analogue) was synthesised and implemented in the detection assay. Method validation for qualitative purpose was performed with respect to specificity, precision (<20%), intermediate precision (<20%), recovery (47-95%), limit of detection (0.2-1 ng/mL), linearity, ion suppression and stability. Two stable isotope-labelled internal standards were used (deuterium-labelled GHRP-4 and GHRP-2 metabolite). The proof-of-principle was obtained by the analysis of excretion study urine samples obtained from a single oral administration of 10 mg of GHRP-2. Here, the known metabolite was detectable over 20 h after administration while the intact drug was not observed.

Optimizing the Mechanical Properties of Ultra-High-Performance Fibre-Reinforced Concrete to Increase Its Resistance to Projectile Impact.

This study describes an extensive experimental investigation of various mechanical properties of Ultra-High-Performance Fibre-Reinforced Concrete (UHPFRC). The scope is to achieve high strength and ductile behaviour, hence providing optimal resistance to projectile impact. Eight different mixtures were produced and tested, three mixtures of Ultra-High-Performance Concrete (UHPC) and five mixtures of UHPFRC, by changing the amount and length of the steel fibres, the quantity of the superplasticizer, and the water to binder (w/b) ratio. Full stress-strain curves from compression, direct tension, and flexural tests were obtained from one batch of each mixture to examine the influence of the above parameters on the mechanical properties. The Poisson's ratio and modulus of elasticity in compression and direct tension were measured. Additionally, a factor was determined to convert the cubic strength to cylindrical. Based on the test results, the mixture with high volume (6%) and a combination of two lengths of steel fibres (3% each), water to binder ratio of 0.16% and 6.1% of superplasticizer to binder ratio exhibited the highest strength and presented great deformability in the plastic region. A numerical simulation developed using ABAQUS was capable of capturing very well the experimental three-point bending response of the UHPFRC best-performed mixture.

A Mechanical Treatment Method for Recycled Aggregates and Its Effect on Recycled Aggregate-Based Concrete.

Recycle concrete aggregates (RCA) consist of natural aggregates and remnant mortar adhered to their surface. The amount, size, and morphology of the adherent remainder paste influences quality aspects of RCA, such as their bonding potential with new cement matrix in an RCA-based concrete, as well as the concrete's overall rheological and performance characteristics. The objective of this research was to study the effect of reducing the adhered mortar in RCA, by means of a mechanical treatment method, on the performance of concrete containing RCA at different percentages. The treatment process was conducted within a concrete mixer truck drum at specific time intervals, the effect of which was determined by means of image analysis, mass loss recordings, and circularity determinations. The effect of size of treated and field RCA, as well as replacement percentages on mechanical performance and durability of high and normal strength concrete mixes, were also investigated. It was concluded that the optimal treatment duration where no further significant removal of adhered paste occurred thereon was 3 h, and concrete mixes containing 3 h treated RCA exhibited comparable performance characteristics to those of the reference concrete mix.

Comprehensive plasma-screening for known and unknown substances in doping controls.

Occasionally, doping analysis has been recognized as a competitive challenge between cheating sportsmen and the analytical capabilities of testing laboratories. Both have made immense progress during the last decades, but obviously the athletes have the questionable benefit of frequently being able to switch to new, unknown and untested compounds to enhance their performance. Thus, as analytical counteraction and for effective drug testing, a complementary approach to classical targeted methods is required in order to implement a comprehensive screening procedure for known and unknown xenobiotics. The present study provides a new analytical strategy to circumvent the targeted character of classical doping controls without losing the required sensitivity and specificity. Using 50 microL of plasma only, the method potentially identifies illicit drugs in low ng/mL concentrations. Plasma provides the biological fluid with the circulating, unmodified xenobiotics; thus the identification of unknown compounds is facilitated. After a simple protein precipitation, liquid chromatographic separation and subsequent detection by means of high resolution/high accuracy orbitrap mass spectrometry, the procedure enables the determination of numerous compounds from different classes prohibited by the World Anti-Doping Agency (WADA). A new hyphenated mass spectrometry technology was employed without precursor ion selection for higher collision energy dissociation (HCD) fragmentation experiments. Thus the mass spectra contained all the desired information to identify unknown substances retrospectively. The method was validated for 32 selected model compounds for qualitative purposes considering the parameters specificity, selectivity, limit of detection (<0.1-10 ng/mL), precision (9-28%), robustness, linearity, ion suppression and recovery (80-112%). In addition to the identification of unknown compounds, the plasma samples were simultaneously screened for known prohibited targets.

Alternative markers for Methylnortestosterone misuse in human urine.

Methylnortestosterone is a progestin and synthetic androgenic anabolic steroid, prohibited by WADA. Methylnortestosterone misuse is commonly detected by monitoring the parent compound and its main metabolites, 17α-methyl-5α-estrane-3α, 17ß-diol (M1) and 17α-methyl-5ß-estrane-3α, 17ß-diol (M2), in the glucuronide fraction. In the current study, a direct detection of methylnortestosterone sulfo-conjugated metabolites after ethyl acetate extraction and analysis by LC/Q/TOF-MS in negative ionization mode was performed, detecting two main sulfate metabolites (S1, S2). For the characterization of metabolites, samples from the excretion study, were additionally analyzed by GC-MS, after solvolysis and per TMS derivatization. RT and MS data collected, were compared with RT and MS data from metabolites of 17z-methyl-5α/ß-estrane-3α/ß, 17z-diols structures with prefixed stereochemistry at 3 and 5 positions, synthesized through Grignard reaction from 19-noretiocholanolone, 19-norandrosterone and 19-norepiandrosterone. Confirmed sulfate metabolites were S1, 17α-methyl-5α-estrane-3α, 17ß-diol 3α sulfate (detected up to 72 h) and S2, 17α-methyl-5ß-estrane-3α, 17ß-diol 3α sulfate (detected up to 192 h). Furthermore, applying targeted analysis based on RT and MS data of the synthesized metabolites two additional metabolites M3, 17ß-methyl-5ß-estrane-3α, 17α-diol and M4, 17ß-methyl-5α-estrane-3α, 17α-diol were detected in the glucuronide fraction and one more metabolite (S3) 17ß-methyl-5ß-estrane-3α, 17α-diol was detected in the sulfate fraction in lower abundance until the end of the excretion study (192 h). Interestingly, S2 could also be detected after the direct analysis of non-hydrolyzed steroid by GC-MS/MS as artifact, following normal ProcIV anabolic steroid procedure and using diethylether as extraction solvent.

Variants in ADIPOQ gene are linked to adiponectin levels and lung function in young males independent of obesity.

BACKGROUND: Obesity is a major risk factor for many chronic diseases, including reduced lung function. The role of polymorphisms of the adiponectin gene, though linked with cardiometabolic consequences of obesity, has not been studied in relation to lung function. OBJECTIVES: The aim of this study is to examine polymorphisms in the ADIPOQ, ADIPOR1, and ADIPOR2 genes in relation to adiponectin serum levels, BMI, and adiposity in 18-year old Cypriot males, as well as determine whether BMI, adipokines levels and polymorphisms in adipokine related genes are associated with lung function levels. RESULTS: From the participants, 8% were classified as obese, 22% as overweight, and the remaining 71% as normal. We found that rs266729 and rs1501299 in ADIPOQ and rs10920531 in ADIPOR1 were significantly associated with serum adiponectin levels, after adjusting for ever smoking. In addition, there was an overall significant increase in FEV1% predicted with increasing BMI (ß = 0.53, 95% CI: 0.27, 0.78) and in FVC % predicted (ß = 1.02, 95% CI: 0.73, 1.30). There was also a decrease in FEV1/FVC with increasing BMI (ß = -0.53, 95% CI: -0.71, -0.35). Finally, rs1501299 was associated with lung function measures. DISCUSSION: Functional variants in the ADIPOQ gene were linked with lung function in young males. Further studies should concentrate on the role of adipokines on lung function which may direct novel therapeutic approaches.