Full Validation Research Articles

DETERMINATION OF RESIDUAL SOLVENTS IN PSMA 11 - AN ACTIVE PHARMACEUTICAL SUBSTANCE IN PSMA-11 KIT FOR Ga-68 LABELLING

A selective, sensitive and low sample consumption GC method for determination of residual solvents in PSMA samples was developed. Selectivity with respect to solvents such as ethanol, diethyl ether, 2-propanole, acetonitrile, dichloromethane, used in manufacturing of PSMA-11, was obtained on two different GC systems and columns. In all these cases, good separation and other system suitability parameters were obtained. The values of detection limit (LOD) and limit of quantitation (LOQ) were estimated and verified experimentally for ethanol, diethyl ether, 2-propanol (IPA), acetonitrile (ACN) and dichloromethane. Full validation parameters i.e.: selectivity, limit of detection (LOD), limit of quantitation (LOQ), linearity, precision, accuracy, robustness and system suitability parameters are presented with respect to ACN and IPA. Accuracy and precision were measured on two GC systems. Statistical tests exhibit, that there are no significant differences in accuracy and precision between two GC systems

Adaptive time multiscale algorithms for fluid–structure interaction with impacts - Application to a row of PWR fuel assemblies under seismic loading

The present article is dedicated to numerical methods for the simulation of the response of PWR fuel assemblies under external mechanical loading such as earthquakes. It proposes new algorithms to manage impact sequences within the time multiscale resolution of a strongly coupled fluid–structure partitioned problem. Preserving the computational efficiency imposes an adaptive strategy to adjust the time scale to force the solution of the costly pressure problem for the fluid only when it is necessary to account for the brutal variations in the structure acceleration resulting from significant impacts. The adaptation criteria must be built upon a thorough monitoring and characterization of all impacts, including the duration of the flight sequence before it occurs and the relative velocity between impact entities. Finally, solutions to mitigate the consequences of missed and unresolved impacts in time are provided to avoid spurious amplification of the variation of the acceleration under impact in the fluid velocity field through the time integration scheme. This leads to two classes of adaptive time multiscale algorithms, extensively tested and qualified through two chosen cases of growing complexity. The paper is completed by a full experimental validation of the proposed fluid–structure framework with contact and impacts, using the results available for a row of six fuel scale assembly immersed in water and submitted to a seismic excitation on a shaking table.

Patterns of synaptic loss in human amyotrophic lateral sclerosis spinal cord: a clinicopathological study

Amyotrophic Lateral Sclerosis (ALS) is mainly characterized by the degeneration of corticospinal neurons and spinal α-motoneurons; vulnerable cells display prominent pTDP-43 inclusions. Evidence gathered from genetics, murine models, and iPSC-derived neurons point to the early involvement of synapses in the disease course and their crucial role in the pathogenic cascade. However, pathology studies, with specimens from large post-mortem cohorts, mapping the pattern of synaptic disturbances over clinical and neuropathological hallmarks of disease progression, are currently not available. Thus, the appearance and progression of synaptic degeneration in human ALS patients are currently not known, preventing a full validation of the murine and in vitro models. Here, we investigated the loss of synaptophysin-positive terminals in cervical, thoracic, and lumbar spinal cord samples from a retrospective cohort of n = 33 ALS patients and n = 8 healthy controls, and we correlated the loss of synapses against clinicodemographic features and neuropathological ALS stage. We found that, although dorsal and intermediate spinal cord laminae do not lose synapses, ALS patients displayed a substantial but variable loss of synapses in the ventral horn of lumbar and cervical spinal cord. The amount of synaptic loss was predicted by disease duration, by the clinical site of onset, and by the loss of α-motoneurons, although not by the fraction of pTDP-43-immunopositive α-motoneurons. Taken together, our findings validate the synaptic pathology observed in other models and suggest that pathogenic pathways unfolding in the spinal microenvironment are critical to the progressive disassembly of local synaptic connectivity.

A smartphone digital image colorimetric method based on nanoparticles for determination of lamotrigine.

Aim: A colorimetric approach for quantification of lamotrigine using spectrophotometric and smartphone image analysis isdescribed in this study. Methods: For full optimization and validation procedures, UV-visible spectroscopy was used, and image analysis was carried out with the help of an app (PhotoMetrix PRO®). Then, as a multivariate calibration method, parallel factor analysis was used fordata analysis. Results: The results demonstrated the capacity of these methods to estimate lamotrigine concentrations in the range of 0.1-7.0μg.ml-1 in exhaled breath condensate, indicating the value of using digital images and smartphone applications in combination with chemometric tools. Conclusion: The image analysis can be superior for its fast and reliable lamotrigine analysis inbiological samples.

Modelling and Control Tank Testing Validation for Attenuator Type Wave Energy Converter - Part I: Experiment Setup and Control-Oriented Modelling

Advanced non-causal optimal control strategies have been demonstrated to significantly improve the energy output of a scale physical model of an attenuator type wave energy converter (WEC) by tank testing experiments using FloWave tank facilities in Edinburgh supported by Wave Energy Scotland's control project. The results are reported in a series of three papers, summarizing the tank testing setup, dynamic modelling, and validation of both linear non-causal optimal control (LNOC) and model predictive control (MPC) in regular and irregular waves. Compared with an optimally tuned passive damping control, both LNOC and MPC can significantly improve the energy output, by between 10% to 460%, using irregular waves with low to medium magnitude and peak periods ranging from <inline-formula xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink"><tex-math notation="LaTeX">$1.7~\mathrm{s}$</tex-math></inline-formula> to <inline-formula xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink"><tex-math notation="LaTeX">$2.8~\mathrm{s}$</tex-math></inline-formula> at <inline-formula xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink"><tex-math notation="LaTeX">$1/20^{th}$</tex-math></inline-formula> scale, as shown in Part II and Part III papers. These controllers also show robust performance in spread waves and side waves which are normally encountered in real sea conditions. Furthermore, the control technologies can be transferred to other types of WECs. The results pave the way for the sea trial testing and full control system validation involving the electricity generation stage and power conditioning stage. This Part I paper will focus on the tank testing setup, the passive damping control experimental results, and the control-oriented models for the WEC. Two state-space models derived respectively from the hydrodynamic model and system identification of experimental data, are validated and compared for use on the controller designs to be presented in Part II and Part III.

The Role of Universities in Achieving the Key Objectives of the Circular Economy Strategy

Abstract The EU’s Circular Economy Action Plan has guided significant changes in recent years in terms of customer behaviour, public or private models and processes. One of the biggest supports came from the education system that plays an important role in ensuring a correct and efficient application of the policy. Therefore, our study is set to fill in the gaps in the current literature by analysing the correlation between the main pillars of circular economy and higher education to determine the existence of such influence and the pattern that each EU member state follows. The results have shown full and partial validations of the considered hypotheses, with the higher education drivers having significant impact on recycling rates and waste generation, and less on the value added to the economy.

Quantification of nine antiretroviral drugs in cerebrospinal fluid: An approach to overcome sample collection tube adsorption

A highly sensitive LC-MS/MS methods were developed and validated to quantify nine antiretrovirals (atazanavir [ATV], tenofovir [TFV], emtricitabine [FTC], darunavir [DRV], dolutegravir [DTG], efavirenz [EFV], lamivudine [3TC], raltegravir [RAL], and ritonavir [RTV]) in human cerebral spinal fluid (CSF). The approach remedies adsorption issues caused by polypropylene based sample collection tubes. 1% ammonium hydroxide in methanol was added in an amount equal to the volume of each quality control (QC) or patient sample. Protein precipitation was utilized with a CSF sample volume of 100 μL and a 100 μL of methanol:ACN and vortexed. Chromatographic separation was achieved with a 3 × 100 ACE® C18 column for ATV, DRV, DTG, EFV, RTV and RAL, and a 2 × 100 Polar RP column for TFV/FTC/3TC. Mobile phase was methanol:water:formic acid (70:30:0.1, v/v/v) for ATV, DRV, DTG, EFV and RTV (10 uL injection, flow rate: 1.00 mL/min), ACN:water:formic acid (35:65:0.1, v/v/v) for RAL (50 uL injection, flow rate: 1.00 mL/min), ACN:water:formic acid (2:98:0.1, v/v/v) for TFV, FTC and 3TC (50 uL injection, flow rate: 0.35 mL/min). Column temperature was 40° C across all assays. The mass spectrometer was operated in positive, multiple-reaction-monitoring (MRM) mode with electrospray ionization (ESI) for all analytes with the exception of EFV, which was operated in negative, MRM mode with ESI. The assay was linear over the calibration range of 1 to 250 ng/mL for all analytes. The addition of 1% ammonium hydroxide in sample tubes overcame up to 44% negative bias in QC samples and allowed the methods to meet full validation criteria.

2D Modelling and energy analysis of entrapped air-pocket propagation and spring-like geysering in the drainage pipeline system

Transient (highly unsteady) air–water two-phase flows and spring-like geysers have been one of the critical concerns in drainage pipeline systems, which may cause or exacerbate drainage flooding problems and associated damage consequences. In this paper, the flow dynamics and energy evolution mechanism of the induced spring-like geysers are innovatively investigated through a two-phase full-2D numerical model developed in this study. After full validation by laboratory experimental tests conducted in this study, the proposed 2D model is systematically applied to simulate transient air–water flows in drainage pipelines. The results have shown acceptable accuracy of this full-2D model to capture the complex flow interactions between the air and water phases, and indicated that the velocity and pressure distribution patterns are highly relevant to the air–water interface deformation and energy exchange. The in-depth energy analysis demonstrates that the intermittent eruption of geysers could be attributed to the conservation and release of different energy forms during the transient air–water two-phase flow process. Besides, the numerical applications for the systems with different boundaries and initial conditions indicate that the different ventilation conditions and initially entrapped air volume may significantly affect the velocity distribution of the air phase, thereby playing an essential role to provide effective measures to mitigate unexpected geyser events and pressure oscillations in the system. The results and findings of this paper could provide insights to improve the theory and practice of transient air–water two-phase flows in drainage pipeline systems.

Department Wide Validation in Digital Pathology—Experience from an Academic Teaching Hospital Using the UK Royal College of Pathologists’ Guidance

Aim: we describe our experience of validating departmental pathologists for digital pathology reporting, based on the UK Royal College of Pathologists (RCPath) “Best Practice Recommendations for Implementing Digital Pathology (DP),” at a large academic teaching hospital that scans 100% of its surgical workload. We focus on Stage 2 of validation (prospective experience) prior to full validation sign-off. Methods and results: twenty histopathologists completed Stage 1 of the validation process and subsequently completed Stage 2 validation, prospectively reporting a total of 3777 cases covering eight specialities. All cases were initially viewed on digital whole slide images (WSI) with relevant parameters checked on glass slides, and discordances were reconciled before the case was signed out. Pathologists kept an electronic log of the cases, the preferred reporting modality used, and their experiences. At the end of each validation, a summary was compiled and reviewed with a mentor. This was submitted to the DP Steering Group who assessed the scope of cases and experience before sign-off for full validation. A total of 1.3% (49/3777) of the cases had a discordance between WSI and glass slides. A total of 61% (30/49) of the discordances were categorised as a minor error in a supplementary parameter without clinical impact. The most common reasons for diagnostic discordances across specialities included identification and grading of dysplasia, assessment of tumour invasion, identification of small prognostic or diagnostic objects, interpretation of immunohistochemistry/special stains, and mitotic count assessment. Pathologists showed similar mean diagnostic confidences (on Likert scale from 0 to 7) with a mean of 6.8 on digital and 6.9 on glass slide reporting. Conclusion: we describe one of the first real-world experiences of a department-wide effort to implement, validate, and roll out digital pathology reporting by applying the RCPath Recommendations for Implementing DP. We have shown a very low rate of discordance between WSI and glass slides.

Hybrid liquid chromatography high resolution and accuracy mass spectrometry approach for quantification of antibody-drug conjugates at the intact protein level in biological samples

Preclinical in vivo and in vitro characterization of Antibody-Drug Conjugates (ADCs) involves the development of several bioanalytical methods to address many drug exposure questions. The current pharma industry approach requires at least three different assays that must be run, i.e., total antibody (mAb), conjugated payload or conjugated mAb, and free payload assays. Herein we present analytical performances of a quantitative hybrid Ligand Binding/Liquid Chromatography High Resolution and Accuracy Mass Spectrometry (LB/LCHRAM) method that can condense much of the necessary bioanalytical information in one method. The method includes an immuno-capture step, and it detects whole ADC molecules. It was applied to plasma mouse samples and showed reliable bioanalytical performance according to full method validation standards. Quantitation using extracted ion chromatograms and deconvoluted mass peaks was evaluated. The limit of quantitation resulted in 0.5ng of protein on column with a linear dynamic range spanning from 0.5 to 10μg/mL. Moreover, lower drug-to-antibody ratio (DAR) ADC species can be simultaneously detected, also enabling qualitative characterization of in vivo ADC conjugation.

Experimental validation and numerical assessment of a temperature-controlled thermoelectric generator concept aimed at maximizing performance under highly variable thermal load driving cycles

Although the internal combustion engine (ICE) dominance in mobility is being challenged, ICE R&D enables a non-disruptive transition towards sustainable transportation through hybridization and carbon neutral fuels. The efficiency improvement of ICE-based mobility through Waste Heat Recovery (WHR) is thus a priority, especially in the area of hybrid, plugin hybrid and long-haul transportation, where the recovery potential is high, and ICEs will still be used for a long time. Thermoelectric (TE) Generators (TEGs) have been assessed as a possible low maintenance WHR solution for long. However, viable market solutions are still not a reality. While material costs are steadily being overcome with novel affordable TE materials, there is still the issue of low average conversion efficiency under realistic driving conditions. This is caused by the fact that the efficiency of TEGs is further deprecated by the big challenge of thermally optimizing the TEGs under highly variable conditions of exhaust flow rate and exhaust temperature during real-world driving. This thermal optimization mainly means that the hot side temperature should be as close as possible to the maximum allowable temperature of the modules, but not higher.The authors have been exploring exhaust heat exchanger (HX) concepts that allow achieving this thermal optimization under highly variable thermal loads by using phase change. The strategy used incorporates the spreading of excess heat along the HX by variable conductance heat pipes (VCHPs) embedded in it, thus enabling to maximize the energy conversion without thermal dilution under low thermal loads or overheating risk under high thermal loads. This was done by pre-regulating the pressure of the non-condensable gas (NCG) present inside the VCHPs so that these devices would start performing the spreading of excess heat from over-heated to under-heated regions of the HX at a precise phase change temperature, optimized to the optimal thermal level of the thermoelectric generators.The merit of the aforementioned strategy was confirmed through modelling and illustrated in previous work. The scientific novelty of present study relatively to previous work by the authors or other researchers is that it finally provides a full experimental validation of this concept with two different prototypes attached to a light duty engine. The experimental proof-of-concept results were successfully compared against predictions. Finally, theoretical performance analysis of the impact of the application on a light duty vehicle in terms of fuel economy and GHG emissions during the WLTC class 3 b was assessed with the help of driving cycle and engine simulations performed with AVL Suite software.The unique heat spreading and temperature control features of the concept were confirmed experimentally. In addition, predictions made by the model were far beyond the current state of the art for light duty automotive TEG generators. Namely, maximum output powers exceeding 2 kW and 1.2 kW were predicted during the WLTC cycle when using commercial bismuth telluride and the silicide-Tetrahedrite modules explored by the authors, respectively. Average fuel/CO2 savings of 4% were predicted for the WLTC cycle, with these savings raising to 12% during the highway portion of the cycle. This unparalleled performance is explained by the possibility of achieving both an optimized hot face temperature and a high heat exchanger effectiveness even under highly variable thermal loads.

Validation of Free Formaldehyde Determination Method in DT Vaccine and Tetanus Toxoid Antigen.

Validation is a Good Manufacturing Practice principle that proves any procedure, process, method, equipment, material, activity, or system actually leads to the expected results. This study validates the method for the determination of free formaldehyde in biological products (including the diphtheria-tetanus vaccine and tetanus toxoid antigen). The operatingprocedure of this method is based on pharmacopoeial monographs. It also does not require full validation, although its suitability under the actual condition of use should be verified. Performance characterizations, such as accuracy, intra-precision (repeatability), intermediate precision (inter-precision), linearity, range, and the limit of quantitation, were investigated and calculated. Accuracy and precision were studied at different concentration levels by spiking known amounts of formaldehyde in real samples. The accuracy and precision results were expressed as the recovery and the relative standard deviation (RSD), respectively. Precision was expressed as intra-precision (repeatability) and inter-precision. Intra-precision or repeatability was performed by one operator in one day by adding three levels of concentration to the products. The inter-precision was conducted by one operator in three individual days within the same laboratory at three concentration levels. Range and linearity were assessed by investigating the correlation coefficient of the regression line between different concentrations of formaldehyde and their response. The acceptance criteria and limits were defined for these validation parameters in these biological products. The RSD for intra-day and inter-day precision studies was less than 5% in a medium concentration of linear range. At this concentration level, accuracy was 90%-110%. The method's linearity ranged between 0.0000039%-0.01% w/v of formaldehyde with a correlation coefficient of 0.9999. The results exhibited sufficient linearity, accuracy, precision, and range. Therefore, this method can be used successfully to determine free formaldehyde for biological products.

Deep Sequencing and Molecular Characterisation of BK Virus and JC Virus WHO International Reference Materials for Clinical Diagnostic Use.

Reactivation of JC and BK polyomaviruses during immunosuppression can lead to adverse clinical outcomes. In renal transplant recipients, BKV-associated nephropathy can result in graft loss, while in patients with autoimmune disorders, prolonged immunomodulatory drug use can cause rare onset of progressive multifocal leukoencephalopathy due to JCV reactivation. In such patients, accurate BK and JC viral load determinations by molecular technologies are important for diagnosis and clinical management; however, comparability across centres requires effective standardisation of diagnostic molecular detection systems. In October 2015, the WHO Expert Committee for Biological Standardisation (ECBS) established the 1st WHO International Standards (ISs) for use as primary-order calibrants for BKV and JCV nucleic acid detection. Two multi-centre collaborative studies confirmed their utility in harmonising agreement across the wide range of BKV and JCV assays, respectively. Previous Illumina-based deep sequence analysis of these standards, however, identified deletions in different regions, including the large T-antigen coding region. Hence, further detailed characterization was warranted. Comprehensive sequence characterisation of each preparation using short- and long-read next-generation sequencing technologies was performed with additional corroborative independent digital PCR (dPCR) determinations. Potential error rates associated with long-read sequencing were minimised by applying rolling circle amplification (RCA) protocols for viral DNA (circular dsDNA), generating a full validation of sequence identity and composition and delineating the integrity of full-length BK and JC genomes. The analysed genomes displayed subpopulations frequently characterised by complex gene re-arrangements, duplications and deletions. Despite the recognition of such polymorphisms using high-resolution sequencing methodologies, the ability of these reference materials to act to enhance assay harmonisation did not appear significantly impacted, based on data generated by the 2015 WHO collaborative studies, but highlights cautionary aspects of IS generation and commutability for clinical molecular diagnostic application.

0308 Impact of Customized Lighting on Sleep in Hospitalized Patients

Abstract Introduction Inpatient sleep may be disrupted for myriad reasons, including lighting exposure that is typically fixed at constant intensity and spectra. In this study we employed customized lighting that promotes circadian entrainment by exposing patients to blue-augmented lighting during the morning and blue-suppressed lighting evening to improve sleep timing and duration. Methods Two Mount Sinai hospital rooms (with 2 beds each) were outfitted with Eight Mattress sensors that use a combination of movement, breathing, heart rate, and temperature variables to estimate wake and sleep vigilance states in 30-second epochs. One room contained customized lighting between 7 am and 11 pm, while the other room contained standard hospital lighting. The current analysis includes 60 participants (30 in the control room and 30 in the custom lighting room), who were matched for time-of-year hospital admission date. We first analyzed the probability of sleep during any given 30-second epoch across each subject’s admission and compared the distributions of sleep probability across the 24-hour cycle for all subjects in the lighting vs control conditions. We additionally evaluated total nocturnal sleep duration(11 PM – 7 AM) by 1) summating all sleep epochs on nights containing at least 50% valid data and 2) normalizing all measured sleep epochs to all valid sleep/wake outputs (excluding indeterminate epochs). Results The distribution of sleep probability was significantly different in the lighting vs control condition (p &amp;lt; 0.001) with most apparent diversion of the distributions between 9 pm and 9 am. The average raw nocturnal sleep duration was significantly higher in lighting condition (270.0 ± 23 minutes vs 201 ± 23 min in control, p = 0.037), as was the average minutes of sleep per hour of valid recording (36.9 ± 15 minutes vs 28.4 ± 13 in control, p = 0.022). There were no significant differences in the number of nocturnal wake or indeterminate epochs between conditions. Conclusion Custom lighting appears to promote sleep in hospitalized patients, but the interpretation is tempered by absence of full validation of the mattress sensor against polysomnography. Future work will evaluate differences in sleep timing and continuity between conditions. Support (if any) McClung Foundation, R01 AG066870

Cross-cultural Adaptation of Oral and Maxillofacial Frailty Assessment Tools for Geriatric Population of Kerala.

The aim of this study is to translate the oral and maxillofacial frailty index (OMFI) into Malayalam, culturally adapt it, and test its reliability and validity in the Kerala geriatric population. OMFI was translated, culturally adapted, and validated in Malayalam using a methodological and cross-sectional study design. The Malayalam version of OMFI underwent full linguistic validation and was tested on 200 patients at Amritakripa Hospital in Kalpetta. Principal component analysis with varimax rotation was used for exploratory factor analysis, and Cronbach's alpha was used to assess reliability. Two-hundred patients were recruited in this study. Participants ranged in age from 60 to 83 years; mean age was 68 years (SD: 15.21). In total 55.5% were male participants, and 30.5% were belonging to upper middle class as per the Kuppuswami scale. Only 12% of the participants were living alone. Kaiser-Meyer-Olkin was found to be 0.583, and Bartlett's test of sphericity was significant with a Chi-square test value of 1003.469. A principal axis factor analysis conducted on 20 items with orthogonal rotation (varimax). OMFI Malayalam version (5 items) had a good internal consistency (Cronbach's alpha = 0.751). Item-total correlations were reviewed for the items of OMFI. The OMFI Malayalam version demonstrated acceptable validity and reliability and can be used to screen the oral frailty of the geriatric population in Kerala. As Kerala is having highest geriatric population in India, we need to assess the oral frailty burden of Kerala. This study provided the first measure to assess the oral frailty in elderly in Kerala.

Use of Isotope-Labeled Body or Dietary Proteins to Determine Dietary Amino Acid Digestibility

Amino acid (AA) digestibility in humans has been determined conventionally based on oro-ileal AA disappearance. With this approach, it is necessary to account for undigested AAs of body origin (endogenous AAs) found in the ileal digesta. Determination of the endogenous AAs under physiological conditions is not straightforward, and the use of isotopes (labeled foods or body tissues) has been pivotal to advancing our understanding. The application of isotopes for determining gut endogenous AAs and AA digestibility is discussed as well as the types of digestibility coefficient generated (apparent, true, real) dependent upon methodology. Recently a new dual isotope-based method for determining ileal AA digestibility in humans has been developed that obviates the collection of ileal digesta. The dual isotope method, which awaits full validation, offers considerable promise for making noninvasive measures of AA digestibility in humans of different ages and physiological states.

Prediction of fatty acid composition in intact and minced fat of European autochthonous pigs breeds by near infrared spectroscopy

The fatty acids profile has been playing a decisive role in recent years, thanks to technological, sensory and health demands from producers and consumers. The application of NIRS technique on fat tissues, could lead to more efficient, practical, and economical in the quality control. The study aim was to assess the accuracy of Fourier Transformed Near Infrared Spectroscopy technique to determine fatty acids composition in fat of 12 European local pig breeds. A total of 439 spectra of backfat were collected both in intact and minced tissue and then were analyzed using gas chromatographic analysis. Predictive equations were developed using the 80% of samples for the calibration, followed by full cross validation, and the remaining 20% for the external validation test. NIRS analysis of minced samples allowed a better response for fatty acid families, n6 PUFA, it is promising both for n3 PUFA quantification and for the screening (high, low value) of the major fatty acids. Intact fat prediction, although with a lower predictive ability, seems suitable for PUFA and n6 PUFA while for other families allows only a discrimination between high and low values.

Simultaneous Quantification of Some Fluoroquinolone Residues in Real Wastewater Effluents Using CZE

Since active pharmaceutical ingredients (APIs) are directly related to human health, monitoring and quantifying them in the environment is a crucial and challenging issue. Using capillary-zone electrophoresis (CZE), four frequently used fluoroquinolones (FQs), ciprofloxacin, sparfloxacin, moxifloxacin, and gatifloxacin, were efficiently isolated and measured in pharmaceutical industrial wastewater. Solid-phase extraction (SPE) was developed and used as an efficient sample pretreatment procedure. The capillary electrophoretic procedure’s various parameters were tuned to produce the optimal separation pattern for the drugs under consideration. All of the drugs under study were quantified in a concentration range of 0.5 to 50 µg/mL. After full assay validation in compliance with ICH-Q2B criteria, real wastewater samples were subjected to effective SPE, and the proposed assay was successfully used to determine the examined FQs in real wastewater samples.

A Novel Stereo Camera Fusion Scheme for Generating and Tracking Real-Time 3-D Patient-Specific Head/Face Kinematics and Facial Muscle Movements

Recovery and rehabilitation of facial mimics need enhanced decision support with multimodal bio-feedbacks from 3D real-time biomechanical head animation. Kinect V2.0 can detect and track 3-D high-definition face features (FFs) but the end of production can lead to difficult deployment of the developed solutions. Deep Neural Network (DNN)-based methods were employed, but the detected features were in 2-D or not accurate in 3-D. So, we developed a novel stereo-fusion scheme for enhancing the accuracy of 3-D features and generating biomechanical heads. Four stereo cameras were employed for detecting 2-D FFs based on DNN-based models. Stereo-triangulated 3-D FFs were fused using the Kalman filter. A head, skull, and muscle network were generated from the fused FFs. We validated the method with 1,000 virtual subjects and 5 Computed Tomography-based subjects. The in-silico trial errors (Mean±SD) were 2.27±0.29mm, 3.15±0.23mm, 1.72±0.13mm, and 3.08±0.39mm for the facial head, facial skull, muscle insertion point, and muscle attachment point regions. The experimental errors were 1.8384±0.1451mm, 2.6937±0.0575mm, 1.8271±0.1242mm, and 3.1428±0.2407mm. The errors were compatible with those using the Kinect V2.0 sensor and smaller than those using monovision-based 3-D feature detectors. This study has four contributions: (1) a stereo-fusion scheme for reconstructing 3-D FFs from 2-D FFs, (2) an enhancement accuracy for 3D DNN-based FF detection, (3) a biomechanical head generation from stereo-fusion cameras, and (4) a full validation procedure for 3-D FF detection. The method will be validated with facial palsy patients. Soft-tissue deformation will be integrated with mixed reality technology toward a next-generation of face decision-support system.

Evaluation of expressed self-contempt in psychotherapy: an exploratory study

ABSTRACT Self-contempt may be a frequent but overlooked clinical phenomenon, associated with a number of psychological problems such as increased sadness and shame. It was shown that self-contempt interferes with productive emotional processing and the quality of therapeutic alliance. This study aims to develop a reliable measure of expressed self-contempt given that a previous three-point assessment may be too restrictive in range, resulting in non-significant results. Thus, the present study applied an extended observer-rated scale to different participant groups in different contexts. This explorative phase focuses on a sample of N = 61 participants divided into three groups, including n = 20 controls, n = 21 patients with a diagnosis of borderline personality disorderand n = 20 patients with a diagnosis of major depressive disorder. Levels of self-contempt are compared between the groups and are associated with symptom indicators. Reliability of the instrument is analysed using inter-rater reliability and internal consistency, which are sufficient. The level of expressed self-contempt is not related to symptom intensity. Patients with borderline personality disorder do not express more self-contempt than the other groups. While further research should establish full validity of the scale, reliability is satisfactory and the use of the scale can be recommended.