Enhanced urinary stability of peptide hormones and growth factors by dried urine microsampling

Volumetric absorptive microsampling (VAMS) and dried urine spot (DUS) strategies were applied for the collection of dried microsamples for anti-doping testing of low-stability peptide hormones and growth factors prohibited by the World Anti-Doping Agency (WADA). Drying, storage and transport conditions, as well as pretreatment steps, were optimised before liquid chromatography - tandem mass spectrometry (LC–MS/MS) analysis. The analytical method has been fully validated in terms of sensitivity (limits of quantitation 0.3−10 ng/mL), precision (RSD% < 6.6 %) and extraction yields (78–91 %). Dried microsample stability studies (90 days) have been performed and compared to fluid urine stability. Significantly higher losses have been observed in fluid urine stored at −20 °C (up to 55 %) and −80 °C (up to 29 %) than in dried urine microsamples stored at room temperature (< 19 %). The final microsampling and analysis protocols allow the collection of urine microvolumes, unlikely to be tampered, stably storable and shippable with no particular precautions for possible anti-doping testing of prohibited peptides and hormones

Frequency and duration of SARS-CoV-2 shedding in oral fluid samples assessed by a modified commercial rapid molecular assay

Background: RT-PCR on nasopharyngeal (NPS)/oropharyngeal swabs is the gold standard for diagnosis of SARS-CoV-2 infection and viral load monitoring. Oral fluid (OF) is an alternate clinical sample, easy and safer to collect and could be useful for COVID-19 diagnosis, monitoring viral load and shedding. Methods: Optimal assay conditions and analytical sensitivity were established for the commercial Simplexa™ COVID-19 Direct assay adapted to OF matrix. The assay was used to test 337 OF and NPS specimens collected in parallel from 164 hospitalized patients; 50 bronchoalveolar lavage (BAL) specimens from a subgroup of severe COVID-19 cases were also analysed. Results: Using Simplexa™ COVID-19 Direct on OF matrix, 100% analytical detection down to 1 TCID50/mL (corresponding to 4 × 103 copies (cp)/mL) was observed. No crossreaction with other viruses transmitted through the respiratory toute was observed. Parallel testing of 337 OF and NPS samples showed highly concordant results (κ = 0.831; 95 % CI = 0.771–0.891), and high correlation of Ct values (r = 0.921; p < 0.0001). High concordance and elevated correlation was observed also between OF and BAL. Prolonged viral RNA shedding was observed up to 100 days from symptoms onset (DSO), with 32% and 29% positivity observed in OF and NPS samples, respectively, collected between 60 and 100 DSO. Conclusions: Simplexa™ COVID-19 Direct assays on OF have high sensitivity and specificity to detect SARS-CoV-2 RNA and provide an alternative to NPS for diagnosis and monitoring SARS-CoV-2 shedding

Transdiagnostic subgroups of cognitive impairment in early affective and psychotic illness

Abstract: Cognitively impaired and spared patient subgroups were identified in psychosis and depression, and in clinical high-risk for psychosis (CHR). Studies suggest differences in underlying brain structural and functional characteristics. It is unclear whether cognitive subgroups are transdiagnostic phenomena in early stages of psychotic and affective disorder which can be validated on the neural level. Patients with recent-onset psychosis (ROP; N = 140; female = 54), recent-onset depression (ROD; N = 130; female = 73), CHR (N = 128; female = 61) and healthy controls (HC; N = 270; female = 165) were recruited through the multi-site study PRONIA. The transdiagnostic sample and individual study groups were clustered into subgroups based on their performance in eight cognitive domains and characterized by gray matter volume (sMRI) and resting-state functional connectivity (rsFC) using support vector machine (SVM) classification. We identified an impaired subgroup (N ROP = 79, N ROD = 30, N CHR = 37) showing cognitive impairment in executive functioning, working memory, processing speed and verbal learning (all p < 0.001). A spared subgroup (N ROP = 61, N ROD = 100, N CHR = 91) performed comparable to HC. Single-disease subgroups indicated that cognitive impairment is stronger pronounced in impaired ROP compared to impaired ROD and CHR. Subgroups in ROP and ROD showed specific symptom- and functioning-patterns. rsFC showed superior accuracy compared to sMRI in differentiating transdiagnostic subgroups from HC (BACimpaired = 58.5%; BACspared = 61.7%, both: p < 0.01). Cognitive findings were validated in the PRONIA replication sample (N = 409). Individual cognitive subgroups in ROP, ROD and CHR are more informative than transdiagnostic subgroups as they map onto individual cognitive impairment and specific functioning- and symptom-patterns which show limited overlap in sMRI and rsFC. Clinical trial registry name: German Clinical Trials Register (DRKS). Clinical trial registry URL: https://www.drks.de/drks_web/ . Clinical trial registry number: DRKS00005042

Association between age of cannabis initiation and gray matter covariance networks in recent onset psychosis

Cannabis use during adolescence is associated with an increased risk of developing psychosis. According to a current hypothesis, this results from detrimental effects of early cannabis use on brain maturation during this vulnerable period. However, studies investigating the interaction between early cannabis use and brain structural alterations hitherto reported inconclusive findings. We investigated effects of age of cannabis initiation on psychosis using data from the multicentric Personalized Prognostic Tools for Early Psychosis Management (PRONIA) and the Cannabis Induced Psychosis (CIP) studies, yielding a total sample of 102 clinically-relevant cannabis users with recent onset psychosis. GM covariance underlies shared maturational processes. Therefore, we performed source-based morphometry analysis with spatial constraints on structural brain networks showing significant alterations in schizophrenia in a previous multisite study, thus testing associations of these networks with the age of cannabis initiation and with confounding factors. Earlier cannabis initiation was associated with more severe positive symptoms in our cohort. Greater gray matter volume (GMV) in the previously identified cerebellar schizophrenia-related network had a significant association with early cannabis use, independent of several possibly confounding factors. Moreover, GMV in the cerebellar network was associated with lower volume in another network previously associated with schizophrenia, comprising the insula, superior temporal, and inferior frontal gyrus. These findings are in line with previous investigations in healthy cannabis users, and suggest that early initiation of cannabis perturbs the developmental trajectory of certain structural brain networks in a manner imparting risk for psychosis later in life

Waveform Modelling for the Laser Interferometer Space Antenna

LISA, the Laser Interferometer Space Antenna, will usher in a new era in gravitational-wave astronomy. As the first anticipated space-based gravitational-wave detector, it will expand our view to the millihertz gravitational-wave sky, where a spectacular variety of interesting new sources abound: from millions of ultra-compact binaries in our Galaxy, to mergers of massive black holes at cosmological distances; from the beginnings of inspirals that will venture into the ground-based detectors' view to the death spiral of compact objects into massive black holes, and many sources in between. Central to realising LISA's discovery potential are waveform models, the theoretical and phenomenological predictions of the pattern of gravitational waves that these sources emit. This white paper is presented on behalf of the Waveform Working Group for the LISA Consortium. It provides a review of the current state of waveform models for LISA sources, and describes the significant challenges that must yet be overcome.Comment: 239 pages, 11 figures, white paper from the LISA Consortium Waveform Working Group, invited for submission to Living Reviews in Relativity, updated with comments from communit

A multi-element psychosocial intervention for early psychosis (GET UP PIANO TRIAL) conducted in a catchment area of 10 million inhabitants: study protocol for a pragmatic cluster randomized controlled trial

Multi-element interventions for first-episode psychosis (FEP) are promising, but have mostly been conducted in non-epidemiologically representative samples, thereby raising the risk of underestimating the complexities involved in treating FEP in 'real-world' services

Sputtered cuprous oxide thin films and nitrogen doping by ion implantation

The structural, optical and electrical properties of sputtered cuprous oxide thin films have been optimized through post-deposition thermal treatments. Moreover we have studied the effects of nitrogen doping introduced by ion implantation followed by the optimized oxidant thermal annealing. Three concentrations have been used, 0.6 N%, 1.2 N%, and 2.5 N%. Along with the preservation of the Cu2O phase, a slight optical band gap narrowing and a significant conductivity enhancement has been observed with respect to the undoped samples. These results can be justified by the absence of further oxygen vacancies promoted by dopant introduction and by the substitution of O atoms by N ones. This lattice configuration has been guaranteed by the post implantation annealing in oxidant atmosphere. The used doping technique represents an original out-of-equilibrium approach toward the formation of low-resistivity contacts on Cu2O films for photovoltaic applications

VAMS and StAGE as innovative tools for the enantioselective determination of clenbuterol in urine by LC-MS/MS

Clenbuterol is a chiral, selective β2-adrenergic agonist. It is administered as a racemic mixture for therapeutic purposes (as a bronchodilator or prospective neuroprotective agent), but also for non-therapeutic uses (athletic performance enhancement, cattle growth promotion). Aim of the present study is to develop an original, enantioselective workflow for the analysis of clenbuterol enantiomers in urine microsamples. An innovative miniaturised sampling procedure by volumetric absorptive microsampling (VAMS) and a microsample pretreatment strategy based on stop-and-go extraction (StAGE) tips were developed and coupled to an original, chiral analytical method, exploiting liquid chromatography with triple quadrupole detection (LC-MS/MS). The method was validated, with satisfactory results: good linearity (r2 ≥ 0.9995) and LOQ values (0.3 ng/mL) were found over suitable concentration ranges. Extraction yield (&gt;87 %), precision (RSD &lt; 4.3 %) and matrix effect (85–90 %) were all within acceptable levels of confidence. After validation, the method was applied to the determination of clenbuterol in dried urine sampled by VAMS from patients taking the drug for therapeutic reasons. Analyte content ranged from 0.8 to 2.5 ng/mL per single enantiomer, with substantial retention of the original drug racemic composition. The VAMS-StAGE-LC-MS/MS workflow seems to be suitable for future application to anti-doping testing of clenbuterol in urine

Optimal seismic retrofitting of reinforced concrete buildings by steel-jacketing using a genetic algorithm-based framework

Retrofitting of existing reinforced concrete (RC) frame structures by steel angles and battens (steel-jacketing) is a commonly employed technique used to retrofit beams and columns against gravity and seismic loads. Steel-jacketing (SJ) effectively provides additional deformation and strength capacity to RC members but its application is associated with noticeable downtime of the building and non-negligible costs, depending on the amount of structural and non-structural manufacturing and materials. This paper presents an optimization framework aimed at the minimization of seismic retrofitting-related costs by an optimal placement (topological optimization) and amount of steel-jacketing reinforcement. In the proposed framework a 3D RC frame fiber-section model implemented in OpenSees is handled by a genetic algorithm routine that iterates reinforcement configurations to match the optimal solution. The feasibility of each solution is controlled by the outcomes of a static pushover analysis in the framework of N2 method. Results will provide optimized location and amount of steel-jacketing reinforcement, showing how effective and sustainable reduction of retrofitting costs is achievable maintaining a specified safety level