Stand-alone Technique Research Articles

Epidermal Growth Factor Intralesional Delivery in Chronic Wounds: The Pioneer and Standalone Technique for Reversing Wound Chronicity and Promoting Sustainable Healing.

The early expectations about growth factors' (GFs') discovery as an undisputed therapeutic solution for chronic wounds progressively eclipsed when they failed to accelerate acute wound closure and restore the healing trajectory of stagnant ulcers. Critical knowledge about chronic wound biology and GF pharmacology was a conundrum at that time. Diabetes undermines keratinocytes' and fibroblasts' physiology, impairing skin healing abilities. Diabetic ulcers, as other chronic wounds, are characterized by hyperinflammation, unbalanced proteolytic activity, catabolism, and free radical cytotoxicity. This hostile scenario for the chemical stability, integrity, and functionality of GFs led to the conclusion that topical administration may jeopardize GFs' clinical effectiveness. Epidermal growth factor (EGF) has a proximal position in tissues homeostasis by activating survival and mitogenic pathways from embryonic life to adulthood. Seminal experiments disclosed unprecedented pharmacological bounties of parenterally administered EGF. Accordingly, the experience accumulated for more than 20 years of EGF intralesional infiltration of diabetic wound bottoms and edges has translated into sustained healing responses, such as low recurrences and amputation rates. This delivery route, in addition to being safe and tolerated, has shown to restore a variety of circulating biochemical markers ordinarily disturbed in diabetic conditions. EGF infiltration triggers a cascade of local fibroblast reactions, supporting its molecular integrity, prolonged mean residence time, and ultimately eliciting its receptor trafficking and nuclear translocation. The intralesional delivery route seems to warrant that EGF reaches wound fibroblasts' epigenetic core, mitigating the consequences of metabolic memory imprinting.

Systematic review of cost-effectiveness studies on cervical cancer screening across Europe

IntroductionCervical cancer (CC) is a type of cancer with poor prognosis when diagnosed in advanced stage with a big socioeconomic burden. The incidence rates have wide variations among European countries depending on the implementation or not of screening, vaccination programs and the human development index (HDI). Most studies on cost-effectiveness of CC screening programs are carried out in countries with a high HDI, however more recent reviews of screening approaches are coming from countries with lower HDI aiming to identify the best screening strategies. Our study aims to identify which are the currently applied and most cost-effective strategies of CC screening in Europe. Materials and methodsThis is a systematic review conducted in three different databases (PubMed, Scopus and ScienceDirect) and reported following the PRISMA guidelines. General key terms for all databases were the following: cost-effectiveness, cervical cancer, screening, Europe. We included studies in English, Italian, Spanish and Bulgarian, published in the last 25 years, reporting data on cost-effectiveness of CC screening, costs and outcome measures. The methodological quality of the articles was evaluated with a standardized tool. ResultsA total of 262 studies were identified and 22 studies were included in the final analysis. In 90.1 % of the economic studies, the new screening strategy was shown to be more cost-effective compared to the current one or compared to no screening. The optimal strategy mostly involved primary HPV testing, combined with cytology or as stand-alone screening technique. Several scenarios differing on starting age and periodicities for CC screening, combination of techniques and triage, were found to be cost-effective and below the willingness to pay (WTP) threshold. The methodology of all included studies was assessed from 10 to 11 on the JBI standardized tool and Drummond 11-point checklist. ConclusionNumerous cost-effective options for CC screening in different European countries were identified in this systematic review. HPV testing, with or without cytology, mainly starting at 30 years of age and repeated every 5 years or more was the most cost-effective technique. Future studies should focus on the most appropriate CC screening approach for each context and setting, also considering HPV vaccination in Europe.

Performance Analysis of Interconnection and Differential Power Processing Techniques under Partial Shading Conditions

Partial shading conditions can cause low output power, hotspots, and a reduced lifespan in photovoltaic arrays. Interconnection (IC) and differential power processing (DPP) can be used to mitigate these effects. When individually applied to an array, these techniques can significantly increase the generated power. A few authors studied the combined use of these schemes under specific conditions such as large-scale arrays or a complex combination of several techniques, making it difficult to identify the individual contribution of each technique. Here, we aimed to determine whether the combined use of a switching-inductor DPP circuit and a total-cross-tied interconnection scheme presents better performance than each standalone technique, using a small-scale photovoltaic array. An array was tested using IC, DPP, and a combination of both techniques, and the array was subjected to 13 shading patterns and two irradiance levels. The performance in each case was assessed using maximum output power, performance ratio, mismatch power loss, and power enhancement indicators. The results showed that a standalone differential power processing circuit presents better performance than when it is combined with an interconnection. The DPP showed performance ratio values of up to 97%, mismatch power losses lower than 36.9%, and a power enhancement of up to 95.9%. The standalone interconnection shows the worst performance among the three techniques.

Cyclic Ion Mobility of Isomeric New Psychoactive Substances Employing Characteristic Arrival Time Distribution Profiles and Adduct Separation.

Analysis of new psychoactive substances (NPS), which is essential for toxicological and forensic reasons, can be made complicated by the presence of isomers. Ion mobility has been used as a standalone technique or coupled to mass spectrometry to detect and identify NPS. However, isomer separation has so far chiefly relied on chromatography. Here we report on the determination of isomeric ratios using cyclic ion mobility-mass spectrometry without any chromatographic separation. Isomers were distinguished by mobility separation of lithium adducts. Alternatively, we used arrival time distribution (ATD) profiles that were characteristic of individual isomers and were acquired for protonated molecules or fragment ions. Both approaches provided comparable results. Calculations were used to determine the structures and collision cross sections of both protonated and lithiated isomers that accurately characterized their ion mobility properties. The applicability of ATD profiles to isomer differentiation was demonstrated using direct infusion and flow injection analysis with electrospray of solutions, as well as desorption electrospray of solid samples. Data processing was performed by applying multiple linear regression to the ATD profiles. Using the proposed ATD profile-based approach, the relationships between the determined and given content of isomers showed good linearity with coefficients of determination typically greater than 0.99. Flow injection analysis using an autosampler allowed us to rapidly determine isomeric ratios in a sample containing two isomeric pairs with a minor isomer of 10% (determined 9.3% of 3-MMC and 11.0% of 3-FMC in a mixture with buphedrone and 4-FMC). The proposed approach is not only useful for NPS, but also may be applicable to small isomeric molecules analyzed by ion mobility when complete separation of isomers is not achieved.

A deep autoencoder network connected to geographical random forest for spatially aware geochemical anomaly detection

Machine learning (ML) and deep learning (DL) techniques have recently shown encouraging performance in recognizing metal-vectoring geochemical anomalies within complex Earth systems. However, the generalization of these techniques to detect subtle anomalies may be precluded due to overlooking non-stationary spatial structures and intra-pattern local dependencies contained in geochemical exploration data. Motivated by this, we conceptualize in this paper an innovative algorithm connecting a DL architecture to a spatial ML processor to account for local neighborhood information and spatial non-stationarities in support of spatially aware anomaly detection. A deep autoencoder network (DAN) is trained to abstract deep feature codings (DFCs) of multi-element input data. The encoded DFCs represent the typical performance of a nonlinear Earth system, i.e., multi-element signatures of geochemical background populations developed by different geo-processes. A local version of the random forest algorithm, geographical random forest (GRF), is then connected to the input and code layers of the DAN processor to establish nonlinear and spatially aware regressions between original geochemical signals (dependent variables) and DFCs (independent variables). After contributions of the latter on the former are determined, residuals of GRF regressions are quantified and interpreted as spatially aware anomaly scores related to mineralization. The proposed algorithm (i.e., DAN‒GRF) is implemented in the R language environment and examined in a case study with stream sediment geochemical data pertaining to the Takht-e-Soleyman district, Iran. The high-scored anomalies mapped by DAN‒GRF, compared to those by the stand-alone DAN technique, indicated a stronger spatial correlation with locations of known metal occurrences, which was statistically confirmed by success-rate curves, Student's t‒statistic method, and prediction-area plots. The findings suggested that the proposed algorithm has an enhanced capability to recognize subtle multi-element geochemical anomalies and extract reliable insights into metal exploration targeting.

Elemental geochemistry insights into source inputs, paleo-productivity, and paleo-depositional conditions of the Montney Formation

The analysis of the elemental composition of sediments provides valuable information about input sources, paleoredox conditions, or paleoproductivity. In this study, 1498 rock samples from six wells within the Triassic Montney Formation in Central Alberta, Western Canada, were analyzed using energy-dispersive X-ray fluorescence (ED-XRF). Wavelength dispersive X-ray fluorescence measurements were used to build and validate a Montney-specific calibration to interpret elemental concentrations from the ED-XRF dataset. The calibration accounted for heterogeneities, matrix variations and unique elemental associations that may be present within the Montney Formation. Sediment input sources are interpreted based on cross-plots of proxy elements to be terrigenous, carbonates and biogenic in origins. Analysis of multiple paleoredox proxies indicated the environment of deposition to be mainly oxic. The ratios of potassium (K) to rubidium (Rb) were used as a paleoclimate proxy. Results suggest the predominance of low chemical weathering attributed to a hot and arid paleoclimate during deposition of Montney Formation sediments. Phosphorous concentrations were determined to be strongly associated with Ca, as such it was interpreted to be inorganically sourced, thereby precluding it from being used to assess paleoproductivity. Excess Si interpreted to be biogenically sourced was used in interpreting moderate and high paleoproductivity for the Montney formation. This work demonstrates the versality of matrix-specific calibrated ED-XRF measurements as a valuable, cost efficient, standalone technique in geochemical analysis for characterizing geological formations.

Pulmonary vein isolation with additional substrate ablation for atrial fibrillation results in an increased risk for the development of atypical atrial flutter

Abstract Introduction Pulmonary vein isolation (PVI) is the cornerstone of atrial fibrillation (AF) catheter ablation. Several extra pulmonary vein (PV) ablation strategies for substrate modification (PVI plus) have been employed to AF patients. It has not been proven that this approach decreases the recurrence of AF, and it could contribute to increase the risk of developing atypical atrial flutter. Methods Patients submitted to AF catheter ablation at our centre between 2005 and 2020 were included. Using logistic regression, we did a retrospective analysis of the association between the application of PVI plus strategies (such as ablation of the cavo tricuspid isthmus (CTI), ganglion plexus, isolation of the superior vena cava (SVC), mitral isthmus ablation and atrial roof line ablation) and the development of atypical flutter later submitted to ablation. Results Five hundred and seventy-five patients were included (64% males, age 57±12 years [between 14 and 81], 68.2% with paroxysmal AF) with > 1-year follow-up. Five hundred and five (87.8%) had PVI alone. From the 575 patients, 11 (1.9%) developed an atypical flutter during the follow-up, which was later submitted to ablation. The crude ODDS of a patient submitted to a PVI plus strategy developing atypical atrial flutter are 13.92 times higher than the one of those submitted to a stand-alone PVI technique, with a p value <0.001 (95% CI 3.96 – 48.87). When adjusted for age and history of heart failure, the ODDS of a patient submitted to a PVI plus strategy developing atypical atrial flutter are 16.29 times higher than the one of those submitted to a stand-alone PVI technique, with a p value <0.001 (95% CI 3.92 – 67.65). Conclusions Additional substrate ablation for AF significantly increases the risk of developing atypical auricular flutter.Characteristics of the study populationCharacterization of PIV plus strategies

Assessment of liquid-liquid partition for the assignment of descriptors for the solvation parameter model

The solvation parameter model uses five system independent descriptors to characterize compound properties defined as excess molar refraction, E, dipolarity/polarizability, S, hydrogen-bond acidity, A, hydrogen-bond basicity, B, and McGowan's characteristic volume, V, to model transfer properties between condensed phases. The V descriptor is assigned from structure. For compounds liquid at 20 °C the E descriptor can be assigned from the characteristic volume and its refractive index. The E descriptor for compounds solid at 20 °C and the S, A, and B descriptors are experimental properties traditionally assigned from chromatographic, liquid-liquid partition, and solubility measurements. In this report liquid-liquid partition constants in totally organic and aqueous biphasic systems are evaluated as a standalone technique for descriptor assignments. Using six totally organic biphasic systems the S, A, and B descriptors were assigned with an average absolute deviation (AAD) of about 0.04, 0.03, and 0.04, respectively, compared with the best estimate of the true descriptor values for 65 compounds. The E descriptor for compounds solid at 20 °C can only be estimated with an AAD of approximately 0.1. For six aqueous biphasic systems the B descriptor is assigned with a lower AAD of 0.028 and higher AAD of 0.08 and 0.05 for the S and A descriptors, respectively, than for the totally organic biphasic systems for compounds with a reliable value for the E descriptor. The preferred system for descriptor assignments utilizes both totally organic biphasic systems (heptane-1,1,1-trifluoroethanol, isopentyl ether-propylene carbonate, isopentyl ether-ethanolamine, heptane-ethylene glycol, heptane-formamide, and 1,2-dichloroethane-ethylene glycol) and aqueous biphasic systems (octanol-water, cyclohexane-water) with the possible substitution of some systems with alternative systems of similar selectivity. For 55 varied compounds this combination of eight organic and aqueous biphasic systems resulted in an AAD of approximately 0.03, 0.02, and 0.02 for the S, A, and B descriptors compared to the best estimate of the true descriptor value. For 30 compounds solid at 20 °C the AAD for the E descriptor of 0.11 is poorly assigned. The relative average absolute deviation in percent (RAAD) corresponds to 9.7 %, 3.1 %. 4.0 % and 8.3 % for E, S, A, and B, respectively, for the eight biphasic systems. Liquid-liquid partition is compared to reversed-phase liquid and gas chromatography as a standalone technique for descriptor assignments.

Complicating the debate: Evaluating the potential of gas-chromatography-mass spectrometry for differentiating prehistoric aceramic tar production techniques

Birch bark tar was used extensively throughout human history. While later ceramic-based production technologies are known, prehistoric aceramic techniques leave little to no archaeological evidence. Experimental tar production attempts to fill this gap and suggest potential techniques. However, their archaeological relevance is unclear. Through an in-depth biomolecular analysis using Gas Chromatography-Mass Spectrometry, this study attempts to differentiate tars produced using four experimental aceramic techniques: condensation, ash mound, pit roll, and raised structure. In doing so we publish the largest collection of GC-MS results of aceramic birch tars. The results show that pentacyclic triterpenoids, characteristic of birch bark, vary between the production techniques in relation to heating exposure and perhaps the tar collection method. This allows for a tentative identification of tars produced through the condensation and ash mound techniques, which were formed consistently using short periods of heating and collected systematically by scraping. In contrast, tars produced using the pit roll and raised structure techniques do not have consistent molecular signatures. Despite the partial success of Gas Chromatography-Mass Spectrometry, the archaeological relevance is questioned because this technique is only applicable to samples from optimum lipid preservation conditions when a high number of pentacyclic triterpenoids are preserved. Therefore, using Gas Chromatography-Mass Spectrometry to determine the transformation methods of organics, like birch bark, may not be an appropriate standalone technique to fairly discuss the technological capabilities of past populations.

Calibration of second harmonic generation technique to probe the field-effect passivation of Si(100) with Al2O3 dielectric layers

Optical second harmonic generation (SHG) can be employed to characterize the passivation quality of semiconducting material interfaces. The interface electric field (EDC) related to the existing charges at and near the interface, including the fixed oxide charges Qox, gives rise to the electric field induced second harmonic phenomenon. In this paper, we calibrate the SHG response for EDC measurement, using Al2O3/SiO2/Si(100) samples with different Qox. To perform this calibration, SHG and capacitance-voltage measurements (to access the electrical field of the samples) were made. The experimental results match well the simulated calibration curve, proving the potential of the SHG as stand-alone characterization technique for dielectric stacks on Si.

Surface energy fluxes and energy balance closure using large aperture scintillometer-based ET station on heterogeneous agricultural landscape in north India

This study was carried out to understand the pattern of surface energy fluxes over a periodical scale and energy balance closure using Large Aperture Scintillometer and Micrometeorological tower. The standalone technique as ‘Scintillometry’ which observes the structure parameter of refractive index based on Monin-Obukhov Similarity theory, has the potential to measure the sensible heat flux precisely. This paper discusses the surface energy balance components and energy balance closure over a period of August 2017 to June 2018. The maximum mean energy fluxes Rn, G, H and LE were observed in September (98.6 Wm-2), May (13.9 Wm-2), June (53.3 Wm-2) and August (82.1 Wm-2), respectively. The overall mean ET was observed at the rate of 1.36 mm day-1 during the study period. This scintillometry technique may further use in evapotranspiration modelling from polar orbiting satellite to geostationary satellite over a heterogeneous and undulated landscape.

A state-domain robust autonomous integrity monitoring with an extrapolation method for single receiver positioning in the presence of slowly growing fault

Single receiver positioning has been widely used as a standard and standalone positioning technique for about 25 years. To detect the slowly growing faults caused by satellite and receiver clocks in single receiver positioning, the Autonomous Integrity Monitoring with an Extrapolation method (AIME) was proposed based on the Kalman filter measurement domain. However, AIME was designed with the assumption of there is the same number of visible satellites at each epoch, which limits its application. To address this issue, this paper proposes a state-domain Robust Autonomous Integrity Monitoring with the Extrapolation Method (SRAIME). The slowly growing fault detection statistics is established based on the difference between the estimates of the state propagator and the posterior state estimation in Kalman filtering. Meanwhile, singular value decomposition is adopted to factor the covariance matrix of the difference to increase computational robustness. Besides, the relevant formulas of the proposed method are theoretically derived, and it is proven that the proposed method is suitable for any positioning model based on the Kalman filter. Additionally, the results of two experiments indicate that SRAIME can detect slowly growing faults in single receiver positioning earlier than AIME.

H2C-TM: A Hybrid High Coverage Test Method for Improving the Detection of HtD Faults in STT-MRAMs

This paper proposes a design-for-testability (DFT) scheme and a test method to improve the detection of hard-to-detect (HtD) faults of STT-MRAMs. The proposed DFT scheme considers HtD faults which are undefined state faults (USFs). These states do not always lead to incorrect functionality during the test process resulting in test escapes. The proposed DFT scheme, which can be deployed as a standalone technique, is called USFA-DFT (an undefined state fault-aware design-for-testability technique). In this scheme, the USF detection is achieved through using a weak write before reading the cell. The weak write overwrites defective cells, causing an incorrect read output, without flipping the content of defect-free cells. To avoid test escapes or yield loss (over-testing) caused by process variation (PV) effects, we make use of a post-silicon calibration scheme. Next, to improve the detectability of HtD faults in STT-MRAMs, we suggest a hybrid high coverage test method (called H2C-TM) which enhances the previous method called LCHC-DFT (a low-cost high-coverage design-for-testability technique) by combining it with USFA-DFT. This test method improves the HtD fault detection, by applying the weak write (controlled by USFA-DFT) before the stressed read operation (controlled by LCHC-DFT). This hybrid approach has a negligible area overhead (3.18% for a 1 kbit array). The results for the performance evaluation of the H2C-TM scheme show that for intra-cell and inter-cell defects, on average, the improvements of 14.4% and 11.3% of HtD fault coverage, compared to those of LCHC-DFT, are achieved. Also, for intra-cell and inter-cell defects, the proposed hybrid approach outperforms USFA-DFT by 49.8% and 49.3% respectively. Finally, in the presence of the process variation, the proposed test method guarantees a robust DFT with only a maximum deviation of 10% from the nominal value.

PO-03-101 PEAK FREQUENCY INITIAL US AND EUROPEAN EXPERIENCE: A NOVEL MEASURE TO DISTINGUISH NEAR-FIELD FROM FAR-FIELD EGM COMPONENTS

Discrimination between near-field (NF) vs. far-field (FF) components in electrograms (EGMs) is mostly based upon intuitive perception of local EGM sharpness. As high-density mapping catheter use has expanded, the difficulty of discerning sub-components across many EGMs in realtime has increased. To date no mapping system had employed a means to quantify this distinction. A novel detection algorithm was designed to identify sharpness of NF EGM components by annotating the highest Peak Frequency (PF) of a signal. To provide insight into first clinical use cases of NF annotation algorithm and PF data. Acute procedure data were prospectively collected from 32 operators at 16 institutions in the US and Europe. All cases were performed on EnSite X system with EnSite OT Near Field software (Abbott). PF information was used as an adjunct to activation or voltage maps via an emphasis layer or as a standalone map (Figure). Choice of mapping tools and technique was at physician discretion. Analysis included ablation cases (n=175) with the following indications: AF (60.6% [54.7% PAF, 45.3%, PsAF; 34.9% redo]), SVT (20.6%), and VT/PVC (18.9%). The NF algorithm was the roving detection option of choice for automated point collection in most cases (96.2% of AF cases, 91.7% SVT, 69.7% VT/PVC). Alternative detections were Last Deflection in VT cases (33%) and First Deflection in PVC cases (29%). When NF was used, correctness of EGM annotation was noted as highly accurate in 93.5% of cases. Standalone PF maps were used as a diagnostic tool in 48 (27.4%) Depth of Activation Insights cases. Bounding values for map display were variable based on use-case to highlight various electrophysiologic phenomena (Table). In an AF use case, PF was used for gap identification (n=6); values were applied at 225±28 Hz, consistent with previously published value of 240Hz (Merino, et al. EHRA 2022). Alternatively in VT/PVC cases, low PF far-field zones were highlighted to assess activation at depth in tissue; mean values were 198±10 Hz. Peak frequency mapping helps distinguish near field from far-field electrograms. PF mapping can be used as (1) a standalone mapping technique to accurately identify near field components and (2) PF mapping can be used as an adjunctive technique to complement activation and voltage maps. PF mapping appears to assist in substrate differentiation, pathway localization, and contact assessment. Further research is warranted on optimal settings for various tissue types and rhythms.Tabled 1Table. Standalone PF mapsValues in HzValues in HzUsed InUsed InUsed InIntention of Map UseColor Range HighColor Range LownAFSVTVT/PVCCritical Isthmus Identification424 +/- 70222 +/- 445YesYesYesDepth of Activation Insights490 +/- 300198 +/- 3010YesYesFF LAA vs NF PV EGM475 +/- 268220 +/- 256YesPV Gap Identification400 +/- 257225 +/- 286YesSlow Pathway Modification231 +/- 4345 +/- 7911YesOther**10YesYesYes Open table in a new tab

A baseline for ensemble-based, time-resolved inflow reconstruction for a single turbine using large-eddy simulations and latent diffusion models

We are interested in reconstructing winds flowing through a turbine on a second-by-second basis over a 10 min window. Previously, we developed a machine learning algorithm that takes in a snapshot of wind speed measurements and generates ensembles of three-dimensional wind field estimates. Here, we use these estimates as initial conditions in large-eddy simulations and reconstruct atmospheric and turbine response dynamic quantities in a synthetic field campaign. In doing so, we establish a baseline for model validation that future time-aware data assimilation techniques will be compared to. In turbine-free case studies, ground truth wind speeds consistently fall within our estimated wind speed distribution for the first 100 s after the simulation start. In simulations with turbines, the wind estimates show a small bias of 0.10 m s−1 and good correlation of 0.80 during the first 100 s. During this window, our estimates of the Blade 1 bending moment and generator power typically span the ground truth, with the estimate of the former performing better overall. In summary, this approach shows promise as a stand-alone technique for reconstructing real-world inflow and turbine dynamics in 1−2 min windows and as a foundation for future time-aware data assimilation techniques.

Validation of Field-Dependent Ion-Solvent Cluster Modeling via Direct Measurement of Cluster Size Distributions.

Ion mobility spectrometry is widely used in analytical chemistry, either as a stand-alone technique or coupled to mass spectrometry. Ions in the gas phase tend to form loosely bound clusters with surrounding solvent vapors, artificially increasing the collisional cross section and the mass of the ion. This, in turn, affects ion mobility and influences separation. Further, ion-solvent clusters play an important role in most ionization mechanisms occurring in the gas phase. Consequently, a deeper understanding of ion-solvent cluster association and dissociation processes is desirable to guide experimental design and interpretation. A few computational models exist, which aim to describe the amount of clustering as a function of the reduced electric field strength, bath gas pressure and temperature, and the chemical species probed. It is especially challenging to model ion mobility under high reduced electrical field strengths due to the nonthermal conditions created by the field. In this work, we aim to validate a recently proposed first-principles model by comparing its predictions with direct measurements of cluster size distributions over a range of 20-120 Td as observed using a High Kinetic Energy Ion Mobility Spectrometer coupled to a mass spectrometer (HiKE-IMS-MS). By studying H+(H2O)n, [MeOH + H + n(H2O)]+, [ACE + H + n(H2O)]+, and [PhNH2 + H + n(H2O)]+ as test systems, we find very good agreement between model and experiment, supporting the validity of the computational workflow. Further, the detailed information gained from the modeling yields important insights into the cluster dynamics within the HiKE-IMS, allowing for better interpretation of the measured ion mobility spectra.

Electrically-evoked oscillating calcium transients in mono- and co-cultures of iPSC glia and sensory neurons.

Activated glia are known to exhibit either neuroprotective or neurodegenerative effects, depending on their phenotype, while participating in chronic pain regulation. Until recently, it has been believed that satellite glial cells and astrocytes are electrically slight and process stimuli only through intracellular calcium flux that triggers downstream signaling mechanisms. Though glia do not exhibit action potentials, they do express both voltage- and ligand-gated ion channels that facilitate measurable calcium transients, a measure of their own phenotypic excitability, and support and modulate sensory neuron excitability through ion buffering and secretion of excitatory or inhibitory neuropeptides (i.e., paracrine signaling). We recently developed a model of acute and chronic nociception using co-cultures of iPSC sensory neurons (SN) and spinal astrocytes on microelectrode arrays (MEAs). Until recently, only neuronal extracellular activity has been recorded using MEAs with a high signal-to-noise ratio and in a non-invasive manner. Unfortunately, this method has limited compatibility with simultaneous calcium transient imaging techniques, which is the most common method for monitoring the phenotypic activity of astrocytes. Moreover, both dye-based and genetically encoded calcium indicator imaging rely on calcium chelation, affecting the culture's long-term physiology. Therefore, it would be ideal to allow continuous and simultaneous direct phenotypic monitoring of both SNs and astrocytes in a high-to-moderate throughput non-invasive manner and would significantly advance the field of electrophysiology. Here, we characterize astrocytic oscillating calcium transients (OCa2+Ts) in mono- and co-cultures of iPSC astrocytes as well as iPSC SN-astrocyte co-cultures on 48 well plate MEAs. We demonstrate that astrocytes exhibit OCa2+Ts in an electrical stimulus amplitude- and duration-dependent manner. We show that OCa2+Ts can be pharmacologically inhibited with the gap junction antagonist, carbenoxolone (100 μM). Most importantly, we demonstrate that both neurons and glia can be phenotypically characterized in real time, repeatedly, over the duration of the culture. In total, our findings suggest that calcium transients in glial populations may serve as a stand-alone or supplemental screening technique for identifying potential analgesics or compounds targeting other glia-mediated pathologies.

A Cognitive Behavioral Family Therapy Approach: The Impact of Divorce on a Hispanic Adolescent with an Eating Disorder

Each year, millions of marriages end up in divorce which can cause teenagers to experience multiple physiological and psychological issues. Cognitive Behavioral Family Therapy (CBFT) has become increasingly popular among family therapists in recent decades, who utilize it either as a stand-alone technique within a system perspective or integrated into other approaches with couples and family therapy. There is a gap in the literature regarding the utilization of CBFT to a divorced family of Hispanic/Latinx descent with an adolescent who developed an eating disorder. The overall aim of this article is to provide insight for marriage and family therapists (MFTs), other mental health professionals, professors/teachers, researchers, and virtually everyone. The researchers hope to provide the ability to conceptualize eating disorders in a way that promotes empathy, compassion, and awareness. Barriers unique to Hispanic/Latinx families, clinical implications, and future directions will be discussed.

ESHRE PGT Consortium data collection XXI: PGT analyses in 2018.

What are the trends and developments in preimplantation genetic testing (PGT) in 2018 as compared to previous years? The main trends observed in this 21st dataset on PGT are that the implementation of trophectoderm biopsy with comprehensive whole-genome testing is most often applied for PGT-A and concurrent PGT-M/SR/A, while for PGT-M and PGT-SR, single-cell testing with PCR and FISH still prevail. Since it was established in 1997, the ESHRE PGT Consortium has been collecting and analysing data from mainly European PGT centres. To date, 20 datasets and an overview of the first 10 years of data collections have been published. The data for PGT analyses performed between 1 January 2018 and 31 December 2018 with a 2-year follow-up after analysis were provided by participating centres on a voluntary basis. Data were collected using an online platform, which is based on genetic analysis and has been in use since 2016. Data on biopsy method, diagnostic technology, and clinical outcome were submitted by 44 centres. Records with analyses for more than one PGT for monogenic disorders (PGT-M) and/or PGT for chromosomal structural rearrangements (PGT-SR), or with inconsistent data regarding the PGT modality, were excluded. All transfers performed within 2 years after the analysis were included, enabling the calculation of cumulative pregnancy rates. Data analysis, calculations, and preparation of figures and tables were carried out by expert co-authors. The current data collection from 2018 covers a total of 1388 analyses for PGT-M, 462 analyses for PGT-SR, 3003 analyses for PGT for aneuploidies (PGT-A), and 338 analyses for concurrent PGT-M/SR with PGT-A.The application of blastocyst biopsy is gradually rising for PGT-M (from 19% in 2016-2017 to 33% in 2018), is status quo for PGT-SR (from 30% in 2016-2017 to 33% in 2018) and has become the most used biopsy stage for PGT-A (from 87% in 2016-2017 to 98% in 2018) and for concurrent PGT-M/SR with PGT-A (96%). The use of comprehensive, whole-genome amplification (WGA)-based diagnostic technology showed a small decrease for PGT-M (from 15% in 2016-2017 to 12% in 2018) and for PGT-SR (from 50% in 2016-2017 to 44% in 2018). Comprehensive testing was, however, the main technology for PGT-A (from 93% in 2016-2017 to 98% in 2018). WGA-based testing was also widely used for concurrent PGT-M/SR with PGT-A, as a standalone technique (74%) or in combination with PCR or FISH (24%). Trophectoderm biopsy and comprehensive testing strategies are linked with higher diagnostic efficiencies and improved clinical outcomes per embryo transfer. The findings apply to the data submitted by 44 participating centres and do not represent worldwide trends in PGT. Details on the health of babies born were not provided in this manuscript. The Consortium datasets provide a valuable resource for following trends in PGT practice. The study has no external funding, and all costs are covered by ESHRE. There are no competing interests declared. N/A.

Diffusion tensor magnetic resonance imaging in differentiation of breast lesions

BackgroundDiffusion tensor imaging (DTI) is a novel approach which uses extra gradients to quantify diffusion in several directions (at least six). The purpose of this research was to determine the role of diffusion tensor magnetic resonance imaging in breast lesion differentiation.ResultsApparent diffusion coefficient (ADC) values were significantly lower in malignant than benign lesions, with a cut-off value of 1.21 × 10−3 mm2/s, this gives a sensitivity of 88.46%, specificity 87.50% and accuracy 86.7%. Values of fractional anisotropy (FA) were higher significantly in malignant compared to benign lesions with a 0.15 cut-off value, has a 95.83% sensitivity, 96.15% specificity, and 95.6%, accuracy. Values of RA were significantly higher in malignant (0.180 ± 0.068) compared to benign lesions, with 0.13 cut-off value. Sensitivity, specificity, and accuracy were, respectively, 91.69%, 92.31%, and 90.2%. Values of λ1 were significantly lower in malignant (1.4 ± 0.453 × 10−3 mm2/s) than in benign (2.19 ± 0.659 × 10−3 mm2/s) lesions with a cut-off value of 1.71 × 10−3 mm2/s. Sensitivity and specificity were, respectively, 95.83 and 96.15%. The combined evaluation by (dynamic contrast enhancement) Sensitivity improved to 100% with DCE and DTI readings, while specificity remained at 95.6%.ConclusionsDTI breast imaging is a noninvasive procedure which demonstrated a high potential utility for cancer detection and serving as a standalone technique or in conjunction with DCE-MRI, the discriminating values of FA, λ1 and λ1–λ3 were high. Their measurements were strongly associated with identification breast malignancy and combined evaluation by DTI parameters and DCE-MRI DTI enhanced the sensitivity, lowered the rate of false-negatives, and completely improved the accuracy of breast lesions differential diagnosis.