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Background: Determination of SARS-CoV-2 variant is significant to prevent the spreads of COVID-19 disease. Methods: We aimed to evaluate the variants of SARS-CoV-2 rate in positive patients in Kanuni Sultan Suleyman Training and Research Hospital (KSS-TRH), Istanbul, Türkiye between 1st January and 30th November 2021 by using RT-PCR method. Results: Herein, 825,169 patients were evaluated (male:58.53% and female:41.47%) whether COVID-19 positive or not [(+):21.3% and (−):78.7%] and 175,367 patient was described as positive (53.2%-female and 46.8%-male) by RT-PCR. COVID-19 positive rate is observed highest in the 6–15- and 66–75-year age range. The frequencies were obtained as SARS-CoV-2 positive (without mutation of B.1.1.7 [B.1.1.7 (U.K), E484K, L452R, B.1.351 (S. Africa/Brazil) spike mutations] as 66.1% (n: 115,899), B.1.1.7 Variant as 23.2% (n:40,686), Delta mutation (L452R) variant as 9.8% (n:17,182), B.1.351 variant as 0.8% (n:1370) and E484K as 0.1% (n: 230). In April 2021, general SARS-CoV-2 and B.1.1.7 variant were dominantly observed. Up to July 2021, B.1.617.2 (Delta variant/ Indian variant) and E484K has been not observed. B.1.351 variant of SARS-CoV-2 has been started in February 2021 at the rarest ratio and March 2021 is the top point. September 2021 is the pick point of E484K. African/Brazil variant of SARS-CoV-2 has been started in February 2021 at the rarest ratio and March 2021 is the top point. September 2021 is the pick point of E484K. When the gender type is compared within the variants, women were found to be more prevalent in all varieties. Conclusions: The meaning of these mutations is very important to understand the transmission capacity of the COVID-19 disease, pandemic episode, and diagnosis of the virus with mutation types. Understanding the variant type is important for monitoring herd immunity and the spread of the disease. [ABSTRACT FROM AUTHOR]

Apolipoprotein E (APOE) is recognized for its role in modulating blood-brain barrier (BBB) permeability in vitro , which may have significant implications for the pathogenesis and progression of neurodegenerative disorders. However, evidence in vivo is contrasting. This study explores the impact of APOE genotypes on BBB integrity among 230 participants experiencing cognitive impairment, encompassing cases of Alzheimer's disease (AD) as well as various non-AD neurodegenerative conditions. To assess BBB integrity, we utilized cerebrospinal fluid (CSF)/serum albumin ratios and CSF/serum kappa and lambda free light chains (FLCs) as indirect markers. Our findings show a dose-dependent increase in BBB permeability in individuals carrying the APOE ε4 allele, marked by elevated CSF/serum albumin and FLCs ratios, with this trend being especially pronounced in AD patients. These results highlight the association of APOE ε4 with BBB permeability, providing valuable insights into the pathophysiology of neurodegenerative diseases. • CSF/serum albumin ratio increased in heterozygous and homozygous APOE ε4 carriers. • Kappa and lambda CSF/serum FLCs ratios increased in homozygous APOE ε4 carriers. • APOE ε4 associated with increased BBB permeability in AD and non-AD participants. [ABSTRACT FROM AUTHOR]

Abstract Background Determination of SARS-CoV-2 variant is significant to prevent the spreads of COVID-19 disease. Methods We aimed to evaluate the variants of SARS-CoV-2 rate in positive patients in Kanuni Sultan Suleyman Training and Research Hospital (KSS-TRH), Istanbul, Türkiye between 1st January and 30th November 2021 by using RT-PCR method. Results Herein, 825,169 patients were evaluated (male:58.53% and female:41.47%) whether COVID-19 positive or not [( +):21.3% and (−):78.7%] and 175,367 patient was described as positive (53.2%-female and 46.8%-male) by RT-PCR. COVID-19 positive rate is observed highest in the 6–15- and 66–75-year age range. The frequencies were obtained as SARS-CoV-2 positive (without mutation of B.1.1.7 [B.1.1.7 (U.K), E484K, L452R, B.1.351 (S. Africa/Brazil) spike mutations] as 66.1% (n: 115,899), B.1.1.7 Variant as 23.2% (n:40,686), Delta mutation (L452R) variant as 9.8% (n:17,182), B.1.351 variant as 0.8% (n:1370) and E484K as 0.1% (n: 230). In April 2021, general SARS-CoV-2 and B.1.1.7 variant were dominantly observed. Up to July 2021, B.1.617.2 (Delta variant/ Indian variant) and E484K has been not observed. B.1.351 variant of SARS-CoV-2 has been started in February 2021 at the rarest ratio and March 2021 is the top point. September 2021 is the pick point of E484K. African/Brazil variant of SARS-CoV-2 has been started in February 2021 at the rarest ratio and March 2021 is the top point. September 2021 is the pick point of E484K. When the gender type is compared within the variants, women were found to be more prevalent in all varieties. Conclusions The meaning of these mutations is very important to understand the transmission capacity of the COVID-19 disease, pandemic episode, and diagnosis of the virus with mutation types. Understanding the variant type is important for monitoring herd immunity and the spread of the disease.

Polyamidoamine epichlorohydrin (PAAE) is a permanent wet strength resin used in papermaking. When applied to paperboard, some amount of resin is retained in the sheet, and some is lost to the white water. The papermaker usually knows the amount of PAAE charged to the pulp but has no idea how much chemical is retained in the sheet. In addition, the influence of PAAE dosage, freeness, zeta potential, and pulp kappa number variability on PAAE retention is not well understood. Factorial design experiments using unbleached and bleached softwood (loblolly pine) kraft pulps were conducted to understand the factors that affect PAAE retention. The results revealed that PAAE retention, wet tear index, and tensile index not only depended on the PAAE charged of the pulp but also depended significantly on the pulp freeness. In lieu of freeness, zeta potential data can be used to predict PAAE retention. In addition, at similar freeness, bleached pulp has the highest retention of PAAE compared to low and high kappa unbleached kraft pulps. The results also suggest that lignin may have potential as a wet strength agent.

We previously developed a computer-assisted image analysis algorithm to detect and quantify the microscopic features of rodent progressive cardiomyopathy (PCM) in rat heart histologic sections and validated the results with a panel of five veterinary toxicologic pathologists using a multinomial logistic model. In this study, we assessed both the inter-rater and intra-rater agreement of the pathologists and compared pathologists' ratings to the artificial intelligence (AI)-predicted scores. Pathologists and the AI algorithm were presented with 500 slides of rodent heart. They quantified the amount of cardiomyopathy in each slide. A total of 200 of these slides were novel to this study, whereas 100 slides were intentionally selected for repetition from the previous study. After a washout period of more than six months, the repeated slides were examined to assess intra-rater agreement among pathologists. We found the intra-rater agreement to be substantial, with weighted Cohen's kappa values ranging from k = 0.64 to 0.80. Intra-rater variability is not a concern for the deterministic AI. The inter-rater agreement across pathologists was moderate (Cohen's kappa k = 0.56). These results demonstrate the utility of AI algorithms as a tool for pathologists to increase sensitivity and specificity for the histopathologic assessment of the heart in toxicology studies. [ABSTRACT FROM AUTHOR]

Polyamidoamine epichlorohydrin (PAAE) is a permanent wet strength resin used in papermaking. When applied to paperboard, some amount of resin is retained in the sheet, and some is lost to the white water. The papermaker usually knows the amount of PAAE charged to the pulp but has no idea how much chemical is retained in the sheet. In addition, the influence of PAAE dosage, freeness, zeta potential, and pulp kappa number variability on PAAE retention is not well understood. Factorial design experiments using unbleached and bleached softwood (loblolly pine) kraft pulps were conducted to understand the factors that affect PAAE retention. The results revealed that PAAE retention, wet tear index, and tensile index not only depended on the PAAE charged of the pulp but also depended significantly on the pulp freeness. In lieu of freeness, zeta potential data can be used to predict PAAE retention. In addition, at similar freeness, bleached pulp has the highest retention of PAAE compared to low and high kappa unbleached kraft pulps. The results also suggest that lignin may have potential as a wet strength agent. [ABSTRACT FROM AUTHOR]

Observer reliability studies for fracture classification systems evaluate agreement using Cohen's κ and absolute agreement as outcome measures. Cohen's κ is a chance-corrected measure of agreement and can range between 0 (no agreement) and 1 (perfect agreement). Absolute agreement is the percentage of times observers agree on the matter they have to rate. Some studies report a high-absolute agreement but a relatively low κ value, which is counterintuitive. This phenomenon is referred to as the Kappa Paradox. The objective of this article was to explain the statistical phenomenon of the Kappa Paradox and to help readers and researchers to recognize and prevent this phenomenon. [ABSTRACT FROM AUTHOR]

Abstract Cocaine disrupts dopamine (DA) and kappa opioid receptor (KOR) system activity, with long-term exposure reducing inhibiton of DA uptake by cocaine and increasing KOR system function. Single treatment therapies have not been successful for cocaine use disorder; therefore, this study focuses on a combination therapy targeting the dopamine transporter (DAT) and KOR. Sprague Dawley rats self-administered 5 days of cocaine (1.5 mg/kg/inf, max 40 inf/day, FR1), followed by 14 days on a progressive ratio (PR) schedule (0.19 mg/kg/infusion). Behavioral effects of individual and combined administration of phenmetrazine and nBNI were then examined using PR. Additionally, ex vivo fast scan cyclic voltammetry was then used to assess alterations in DA and KOR system activity in the nucleus accumbens before and after treatments. Chronic administration of phenmetrazine as well as the combination of phenmetrazine and nBNI—but not nBNI alone—significantly reduced PR breakpoints. In addition, the combination of phenmetrazine and nBNI partially reversed cocaine-induced neurodysregulations of the KOR and DA systems, indicating therapeutic benefits of targeting the DA and KOR systems in tandem. These data highlight the potential benefits of the DAT and KOR as dual-cellular targets to reduce motivation to administer cocaine and reverse cocaine-induced alterations of the DA system.

This study aims to quantify the site attenuation parameter, kappa (κ), in the southeastern flank of the Red Sea rifting system. To determine κ, a least-squares best-fit method was applied to three-component seismograms, allowing for the modelling of the Fourier amplitude spectra of S-waves. The dataset consisted of 53 earthquakes, ranging in local magnitudes from 3.0 to 4.8 ML. The estimates of κ for 17 sites in the southeastern flank of the Red Sea region revealed average values ranging from 0.026 ± 0.01s to 0.053 ± 0.01s. A statistical analysis of κ dependence on epicentral distance, near-surface geology, and earthquake magnitude demonstrated the dependence of κ on distance and surface geology rather than earthquake magnitudes. The spatial distribution of the parameter κ, which includes both path and site effects, shows higher values at soft rock sites in the eastern region than hard rock sites in the western area. Owing to surface geological conditions, the site-dependent parameter κo exhibited average values of 0.002 ± 0.003s and 0.024 ± 0.002s for the hard and soft rocks, respectively. The results may be used to improve seismic hazard assessments and earthquake ground motion simulations.

Modulation of corticostriatal plasticity alters the information flow throughout basal ganglia circuits and represents a fundamental mechanism for motor learning, action selection, and reward. Synaptic plasticity in the striatal direct- and indirect-pathway spiny projection neurons (dSPNs and iSPNs) is regulated by two distinct networks of GPCR signaling cascades. While it is well-known that dopamine D2 and adenosine A2a receptors bi-directionally regulate iSPN plasticity, it remains unclear how D1 signaling modulation of synaptic plasticity is counteracted by dSPN-specific Gi signaling. Here, we show that striatal dynorphin selectively suppresses long-term potentiation (LTP) through Kappa Opioid Receptor (KOR) signaling in dSPNs. Both KOR antagonism and conditional deletion of dynorphin in dSPNs enhance LTP counterbalancing with different levels of D1 receptor activation. Behaviorally, mice lacking dynorphin in D1 neurons show comparable motor behavior and reward-based learning, but enhanced flexibility during reversal learning. These findings support a model in which D1R and KOR signaling bi-directionally modulate synaptic plasticity and behavior in the direct pathway.

In our study, we estimated earthquake source parameters and spectral decay characteristics of 378 seismograms corresponding to 80 small earthquake events with magnitudes ranging from 1.5 to 3.5. These earthquakes occurred between July 2011 and May 2012 in the Siang region of the Arunachal Himalaya which is not well-studied. To estimate source parameters, the classical Brune model is employed and through the analysis, a scaling relationship is established between the estimated corner frequency ( f c ) and seismic moment ( M 0 ), which can be expressed as M 0 = 1 × 1 0 22 f c - 3.18 . This relationship is in close agreement with previous studies conducted in the Arunachal and Himachal Himalaya regions. It provides support for deviations from self-similarity in the study area, offering valuable insights into the tectonics and structural heterogeneity beneath the Arunachal Himalaya. Our analysis revealed variations in source radius, ranging from 154.4 m to 312.6 m, and seismic moment, spanning from 2.37 × 1011 N-m to 9.32 × 1013 N-m. Interestingly, we observed an increasing trend in stress drop, ranging from 0.013 MPa to 3.26 MPa, within the same range of seismic moment. This significant variation in stress drop primarily occurs in the upper 10–15 km of the Earth's crust, indicating shear brittle failure in this upper crustal region. Furthermore, we conducted an in-depth examination of spectral parameters, including f c high-cut frequency (fmax), and high-frequency spectral decay parameter kappa (κ). Our study highlighted the dependence of κ and fmax estimates on both source characteristics and propagation path, with the source having the most substantial influence. This observation was substantiated through statistical analyses. Additionally, we explored the effect of recording site characteristics on κ and observed a significant contribution of shallow geology at the recording site. This was evident through a negative correlation between the site component of κ (κ0) and VS30, indicating that the local geology of the recording site plays a significant role in spectral parameter estimation. Based on our comprehensive data analysis and statistical observations, we conclude that the variations in source and decay parameters for earthquakes of different magnitudes are attributed to the diverse structural heterogeneities and complex seismotectonic processes underlying the Arunachal Himalaya region. [ABSTRACT FROM AUTHOR]

The Child Attachment Interview (CAI) has demonstrated promise in youth, yet widespread use is thwarted by the need for interview transcription, face-to-face training, and reliability certification. The present study sought to examine the empirical basis for these barriers. Thirty-five archival CAIs were re-coded by: (1) expert coders (i.e., trained and reliable) without access to transcripts, (2) trained coders who had not completed reliability training, and (3) novice coders who had no formal training. Agreement with consensus classifications was computed with the expectation of moderate agreement. Results supported coding by experts without transcription of the interview. Near-moderate agreement preliminarily supported the use of trained coders who have not attempted reliability certification with appropriate caveats. While moderate agreement was not achieved for novice raters, findings suggest that self-paced training options for the CAI may hold future promise. These contributions erode a number of significant barriers to the current use of the CAI. [ABSTRACT FROM AUTHOR]

Background Unilateral spatial neglect (USN) is a common post-stroke cognitive impairment that severely affects the functional recovery and quality of life of patients. Therefore, objective assessment of USN is essential to facilitate patients' functional recovery. Objective To investigate the feasibility of using adynamic eye-tracking task to assess USN in sub acute stroke patients. Methods Thirty inpatients in the sub acute phase after stroke in Department of Rehabilitation Medicine, Nanchong Central Hospital were recruited from September 2021 to July 2022. USN was assessed using the Behavioral Inattention Test-Conventional (BIT-C), Catherine Bergego Scale (CBS), and a two-minute dynamic eye-tracking task within one week of admission by two professional rehabilitation therapists, and adverse effects during the assessment were recorded. USN was diagnosed by a CBS score >0, a total BIT-C score

This study examines shear-wave velocity structures in the Jeju region utilizing horizontal-to-vertical spectral ratios (HVSRs) of environmental noise, focusing on identifying significant low-velocity layers (LVLs). Although conventional methodologies predominantly involve borehole and active seismic exploration, recent advancements in the diffuse-field theory of seismic waves have offered a theoretical foundation for this approach. In the volcanic region of Jeju Island characterized by unique geological features, a pervasive LVL composed of quaternary marine sediments and the Seoguipo sedimentary layer has been observed. These components are crucial for site amplification and attenuation in seismic microzonation. The present study introduces a novel discovery of a distinct LVL, specifically at the UDO site, suggesting that its origin may be attributable to a local magmatic intrusion event. Advanced algorithms and HVSR curve analysis have enabled reliable inversion processes, enhancing the comprehension of the subsurface geology of Jeju. These insights are essential for seismic microzonation practices and contribute significantly to the development of seismic design standards in the Jeju region. [ABSTRACT FROM AUTHOR]

Objective: This study aims to examine the effects of virtual reality (VR) usage on the eyes and investigate the parameters responsible for the subsequent discomfort sensation. Materials and Methods: This prospective study enrolled 20 healthy volunteers who were engaged in a 10-minute VR game session. Refractive errors, kappa angles, phoria presence, accommodative responses, and scotopic, mesopic, and photopic pupillometry values were recorded before and after using VR. A Virtual Reality Sickness Questionnaire (VRSQ) was applied to assess discomfort, and the relation with evaluated parameters was investigated. Results: Twenty volunteers (mean age 29.80±0.57 years) included 11 females (55%) and 9 males (45%). The mean spherical equivalent refractive error was -- 1.94±0.28 diopters and 5 (25%) volunteers had phoria. Average kappa angles were 0.23±0.02 mm (x-axis) and 0.11±0.01 mm (y-axis). Post-VR, the median [(interquartile range (IQR)] stereopsis decreased from 30 (30-60) to 60 (60-60) arc seconds (P<0.001). Pupil sizes increased significantly across all lighting conditions (P<0.001). Accommodation did not significantly change post-VR (P>0.05). VRSQ scores correlated positively with phoria and kappa-x angle (r=0.458, P=0.003 and r=0.330, P=0.038) while negatively with stereopsis and kappa-y angle (r=-0.375, P=0.017 and r=-0.326, P=0.04). Conclusion: Virtual reality use reduces depth perception and induces significant mydriasis across lighting conditions. Post-VR discomfort feeling may be related to phoria, kappa angle, and stereopsis. [ABSTRACT FROM AUTHOR]

The World Health Organization (WHO) recommends the use of color-coded cardiovascular disease (CVD) risk charts for CVD management. This study evaluated the agreement between the laboratory and non-laboratory 10-year CVD risks based on 2019 WHO CVD risk-prediction charts. The agreement of CVD risk scores among 40- to 69-year-old Bhutanese population stratified by gender and age groups (<60 and ≥60 years) was determined via weighted kappa statistics. In the general population, there was substantial agreement between the two CVD risk score charts for all ages and <60 years but a moderate agreement for participants aged ≥60 years. In males, substantial agreement was observed in all ages and in <60 years and moderate agreement in ≥60 years. In females, both the predictions showed substantial agreement in all ages and <60, but a moderate agreement for ≥60 years. The non-laboratory-based risk charts can be used interchangeably with laboratory-based charts for predicting 10-year CVD risk in resource-constrained countries like Bhutan. [ABSTRACT FROM AUTHOR]

Kappa (the high-frequency spectral decay slope at near-source distances; often referred to as κ0) is determined at 25 seismograph stations in Eastern Canada using broadband ground-motion modeling approaches. The database comprises Fourier spectra (effective amplitude spectrum for the horizontal component and the vertical component, 0.8-40 Hz) computed from 3318 earthquakes of moment magnitude M 1.5-5 recorded on stations within 150 km. Average kappa values for bedrock sites, having shear-wave velocities from 850 to 2400 m/s, are highly variable, ranging from -29 to +21 ms (horizontal) and -28 to +11 ms (vertical), but appear on average to be near-zero. The values obtained are sensitive to methodology, especially the necessary adjustments to the spectra to account for site amplification effects. Kappa values do not appear to correlate well with site parameters such as rock shear-wave velocity, average shear-wave velocity in the upper 30 m, primary wave velocity, site class, type and age of rock, or instrument housing. This lack of correlation may reflect the noted sensitivities to methodological factors. We conclude that kappa values in rock environments are not reliably estimated from such proxies and should be determined from recorded ground motions at a given location. On average, there is little evidence of significant high-frequency attenuation on rock sites beyond that already accounted for in ground-motion modeling by the empirical parameterization of regional Q-related path effects. [ABSTRACT FROM AUTHOR]

Objectives: Urinalysis is a first-line test for screening for urinary tract infection. Several devices performing strip and sediment analysis have been introduced. The aim of this study was to compare the performance of Labsan Tricell-1000 and Dirui FUS-2000 automated urine analyzers with manual microscopy. Methods: 463 urine samples were analyzed. Digital image processing and particle recognition automatically display the cells in a flowing sheath fluid mixed monolayer urine sample, take the pictures of particles via digital camera, analyse these pics with a particle recognition software, transfer images of the formed elements to the screen and allow well-trained personnel to select, reclassify or remove them. Manual microscopy was used for comparison. Results: Agreement between Tricell-100 and manual microscopy was very good for RBC (ϰ = 0.80), and WBC (ϰ = 0.83); good for CaOx (ϰ = 0.69), SEC (ϰ = 0.80), YLC (ϰ = 0.72), HC (0.69) and LC (ϰ = 0.64); moderate for BAC (ϰ = 0.51), APC (ϰ = 0.43) and MT (ϰ = 0.55); fair for GC (ϰ = 0.39) and RTEC (ϰ = 0.32). Conclusions: Labsan Trion TriCell-1000 demonstrated satisfactory performance and can be used in routine urinalysis. In the case of low counts of RBC, presence of yeast, crystal, casts or cell clumping in urine sediment, characterization of urine particles should be performed by manual microscopy.

BackgroundAppropriate use criteria (AUC) provide patient-centered physician guidance in test selection. An initial set of AUC was reported by the American Society of Dermatopathology (ASDP) in 2018. AUC reflect evidence collected at single timepoints and may be affected by evolving evidence and experience. The objective of this study was to update and expand AUC for selected tests.MethodsRAND/UCLA (RAND Corporation [Santa Monica, CA]/University of California Los Angeles) methodology used includes the following: (a) literature review; (b) review of previously rated tests and previously employed clinical scenarios; (c) selection of previously rated tests for new ratings; (d) development of new clinical scenarios; (e) selection of additional tests; (f) three rating rounds with feedback and group discussion after rounds 1 and 2.ResultsFor 220 clinical scenarios comprising lymphoproliferative (light chain clonality), melanocytic (comparative genomic hybridization, fluorescence in situ hybridization, reverse transcription polymerase chain reaction, telomerase reverse transcriptase promoter), vascular disorders (MYC), and inflammatory dermatoses (periodic acid-Schiff, Gömöri methenamine silver), consensus by panel raters was reached in 172 of 220 (78%) scenarios, with 103 of 148 (70%) rated "usually appropriate" or "rarely appropriate" and 45 of 148 (30%), "appropriateness uncertain."LimitationsThe study design only measures appropriateness. Cost, availability, test comparison, and additional clinical considerations are not measured. The possibility that the findings of this study may be influenced by the inherent biases of the dermatopathologists involved in the study cannot be excluded.ConclusionsAUC are reported for selected diagnostic tests in clinical scenarios that occur in dermatopathology practice. Adhering to AUC may reduce inappropriate test utilization and improve healthcare delivery.

La variabilidad de los suelos depende de la interacción de covariables ambientales que intervienen en su formación. En México, se registran 25 grupos de suelo de los 32 que incluye la Base Referencial Mundial (BRM). Este estudio identifica el orden de importancia de 11 covariables ambientales, utilizando el modelo no paramétrico basado en un algoritmo de aprendizaje automático supervisado denominado random forest, el cual caracteriza 19 grupos de suelo que incluyen el 99.2% del territorio nacional. Las covariables que se incluyeron fueron, curvatura, densidad de drenaje, distancia al cauce más cercano, geología, índice de aridez, índice de humedad topográfica, índice de posición topográfica, índice de vegetación de diferencia normalizada (NDVI), radiación, rugosidad y temperatura. Los resultados mostraron un total de 100 árboles de clasificación, con una precisión global de 81.83% del modelo a través de random forest y un valor de Kappa de 0.80, expresado como muy bueno. La precisión de disminución promedio mostró que, las cinco covariables analizadas más importantes que clasifican los 19 grupos de suelo son, índice de posición topográfica, índice de aridez, curvatura, radiación y densidad de drenaje.

Producing mineral potential model using GIS software has been increased over the past years. In this study, predictive map consisted of argillic alteration, philic alteration, iron oxide alteration, reduction to pole of aeromagnetic data, lineaments, cu geochemistry anomaly, and principal component analysis (component 3) were prepared from Shahre Babak area. For training model, 37 mineralized points were used. Point pattern analysis was used as well for making non-deposit points and for training model, percepteron artificial neural network with two layers was applied. The training model was used to prepare the final mineral potential model. Based on the mentioned model, the main promising areas were identified to be in the northwest and eastern part of the studied area. Moreover, two areas in the northern and southwestern parts of this area were identified for additional studies. For evaluating the model, ROC curve was used. ROC curve shows high precision of the produced model. For more evaluating, sensitivity, specificity, positive predict value, negative predict value, accuracy, and kappa were computed. The coefficients confirm the high accuracy of the mineral potential model. Introduction Mineral prospectivity mapping (MPM) is a multicriteria decision-making task that aims to outline and prioritize prospective areas for exploring undiscovered mineral deposits of the type sought (Carranza and Laborte, 2015; Yousefi and Carranza, 2015; Sun et al., 2019). In the early stages of exploration, if there are enough known indices in an area, data-driven modeling is proper for mineral potential prospectivity. In this method, at first, all the characteristics of the known indices, of the type of mineralization sought, are collected and the relationship of these characteristics with evidence and spatial patterns is quantified. Then, points with similar characteristics are searched in those areas. Shahre Babak as the studied area is a part of Urumieh-Dokhtar zone. Urumieh-Dokhtar zone is proper for porphyry copper deposits. In this study, at the first stage, conceptual model was defined for porphyry copper modelling. Then, based on the model, some predictive layers were made ready and the data were imported to the trained model of artificial neural network in MATLAB 2021. At the next stage, final model was presented. Material and methods For constructing mineral potential model, a conceptual model was defined. Based on this model, some predictive layers consisted of argillic alteration, iron oxide alteration, phillic alteration, reduction to pole of airborne magnetic map, cu geochemistry anomaly, principal component geochemistry anomaly, intrusive units, lineaments structures, and digital elevation models were made in ARCGIS in raster formats. The pixel size of the raster files is 100m*100m. After fuzzification of raster files, these features were extracted to ASCII formats. Geology data (Intrusive body, faults, and dykes) Shahre Babak geology map in 1:250000 scale was used for extracting geological information. The intrusive bodies, faults, and dykes were extracted from Shahre Babak geology map. After extracting geological information, based on the Euclidean distance, the distance maps were made in ARCGIS. Then these maps became fuzzy. Airborne magnetic data The airborne magnetic data were surveyed by Atomic Energy Organization of Iran (AEOI) during 1977 and 1978. The flight lines distance and the sensor altitude were about 500 and 120 m, respectively. The reduction to pole filter was applied on total magnetic intensity map. Geochemistry data Geochemistry data in 1:250000 scale was used for geochemical interpretations. The cu geochemistry anomaly was drawn from the data. Principal component analysis method was applied on geochemical data. Component 3 was extracted from the data. Aster data Band ratio method was used for extracting the alterations. Iron oxide alteration, philic alteration, and argillic alteration were drawn in ENVI software in raster format. The iron oxide, argillic, and philic alteration files were imported to ARCGIS software and transformed to shapefile format. The distance maps were drawn based on the Euclidean distance. Then these maps became fuzzy. Digital Elevation Model Digital Elevation Model (DEM) was extracted from Aster data. The data became fuzzy. Training dataset For training model, 37 deposit points were selected. Point pattern analysis was used for non-deposit points. Based on this method, 37 non-deposit points were extracted of the Shahre Babak (the studied area). Each of the labels was located in a unique pixel. The features of these points were extracted from the predictive maps. Then these points were imported to artificial neural network (perceptron neural network with two layers). 70% of data were used for training model and 30% were used for testing model. Then the trained model was applied on the ASCII format. The resulting model was drawn using ARCGIS. Artificial neural network ANN is a modelling approach that simulates human brain system inspired by biological neural networks (Celik and Basarir, 2017). ANN can be effectively applied for pattern recognition in a wide variety of geoscience investigations. In this network, the neurons of different layers are interconnected to exchange information in a unidirectional way starting from the input layer through hidden layers to the output layer (Rodriguez-Galiano et al., 2015; Celik and Basarir, 2017). The flow of information is performed by assigning weights to the connections of different neurons (Rodriguez-Galiano et al., 2015). The back-propagation algorithm is employed to ensure the learning capability of ANN. This algorithm computes the error between the outputted value and real target value, then feeds back it to ANN in order to adjust the weights and biases (Celik and Basarir, 2017). Results Mineral potential map of studied area was produced by artificial neural network. Based on resulting model, the first-class promising areas were detected in north western and eastern parts of the studied area. Moreover, two areas in north and south western parts of studied area were identified. For evaluating the model, ROC curve was used. This curve shows model accuracy with high precision. For further evaluation, sensitivity, specificity, positive predictive value, negative predictive value, accuracy, and kappa were calculated with 94.7%, 91.8%, 92.3%, 94.4%, 93.3%, and 89%, respectively. These coefficients also confirm the high accuracy of the mineral potential model.

Following repeated opioid use, some dependent individuals experience persistent cognitive deficits that contribute to relapse of drug-taking behaviors, and one component of this response may be mediated by the endogenous dynorphin/kappa opioid system in neocortex. In C57BL/6 male mice, we find that acute morphine withdrawal evokes dynorphin release in the medial prefrontal cortex (PFC) and disrupts cognitive function by activation of local kappa opioid receptors (KORs). Immunohistochemical analyses using a phospho-KOR antibody confirmed that both withdrawal-induced and optically evoked dynorphin release activated KOR in PFC. Using a genetically encoded sensor based on inert KOR (kLight1.2a), we revealed the in vivo dynamics of endogenous dynorphin release in the PFC. Local activation of KOR in PFC produced multi-phasic disruptions of memory processing in an operant-delayed alternation behavioral task, which manifest as reductions in response number and accuracy during early and late phases of an operant session. Local pretreatment in PFC with the selective KOR antagonist norbinaltorphimine (norBNI) blocked the disruptive effect of systemic KOR activation during both early and late phases of the session. The early, but not late phase disruption was blocked by viral excision of PFC KORs, suggesting an anatomically dissociable contribution of pre- and postsynaptic KORs. Naloxone-precipitated withdrawal in morphine-dependent mice or optical stimulation of pdynCre neurons using Channelrhodopsin-2 disrupted delayed alternation performance, and the dynorphin-induced effect was blocked by local norBNI. Our findings describe a mechanism for control of cortical function during opioid dependence and suggest that KOR antagonism could promote abstinence.

Objective: To determine the effectiveness of ten therapeutic exercises on the patients of Oro-pharyngeal Dysphagia (OD) clinically diagnosed with one structural disorder (Head and neck cancer; HNC) and two neurological disorders (Traumatic Brain Injury; TBI and Cerebral Vascular Accidents; CVA). Methodology: The Quasi experimental study (pretest-posttest design) was conducted, gathering a sample of 75 patients with mild to moderate Oro-pharyngeal Dysphagia (OD) severity through purposive sampling technique from Govt. and private hospitals without no age and geneder limits. The patients with neurological diseases, nasogastric (NG) tube and tracheostomy were excluded. Two screening test (a) Glassgow Coma Scale (GCS) and (b) The Repetitive Saliva Swallowing Test (RSST) were used to investigate patient’s consciousness and voluntarily swallow, respectively. To quantify the effectiveness of therapeutic manual, The Eating Assessment Tool (EAT-10) was employed as baseline (pre-test and post-test). Therapeutic protocol was received by the patients twice a week for six weeks in the clinical setting and post test was administered on patients’ follow-ups and some through online calls. Results: Using SPSS version 26, Shapiro-Wilk test demonstrated normality in the data distribution showing kurtosis (+10, -10) and skewness (+3, -3) values falling within their ranges. Consequently, parametric tests: One-way between-subject ANOVA was employed to compare the statistical significant mean difference between the groups (HNC, TBI, CVA) on EAT-10 score measuring the effect of therapeutic exercises manual for OD. Paired sample t-test was run to investigate the mean difference of EAT-10 scores within subjects before and after the implication of therapeutic exercises manual. One-way between-subject ANOVA identified a significant mean difference of EAT-10 score between three groups F (2, 72) = 17.64, p< .05, with large effect size (η2= .970). Paired sample t-test results indicated a significant mean difference (t= 80.884, df= 74, p< .005, one-tailed) with large effect size (d = .82) within the subjects before and after the intervention. Conclusion: So, findings addressed a large improvement in Oro-Pharyngeal Dysphagia after the implementation of therapeutic exercises manual.

Objective: To reduce and eliminate aspiration and penetration ultimately, it was aimed to develop the indirect therapeutic exercises manual for patients with Oro-pharyngeal Dysphagia. Methodology: The study based on analytical approach: a method for tool development, was conducted on the sample of five experts and one hundred speech and language pathologists through purposive sampling in clinical setting (from Nov 2021 to Sep 2022). The factors via already existed literature data base; speech BITE; MEDLINE; PakMediNet; PubMed; Web of Science; CINAHL; IndMed and Google Scholar were generated. The factors were divided into two domains/ latent variables (compensatory strategies and rehabilitative techniques) with fourteen items/ observable variables (relevant instructions). These domains and items were further modified into ‘content validity performa. Content validity was assessed through ‘face to face written and verbal reviews’ by panel of five experts on the content validity performa. The refined and simplified factors (domains and fourteen items) were altered into an online survey based on five points Likert scale of preferences. One hundred speech and language pathologists from different regions of the Punjab were approached to participate in an online survey so the correlation between the domains and items can be found out. Results: Content Validity Index (CVI), Content Validity Ratio (CVR) and kappa statistics were employed to calculate the content validity. The findings suggested that the therapeutic exercises manual met the satisfactory level of content validity (CVI= CVR= kappa= 0.85). To confirm the factor validity via Likert scale, AMOS version 23 was employed, suggesting fit in model (x2 (76) = 80.255, p .04). The internal consistency (Cronbach Alpha) of therapeutic exercises manual was 0.833 and the inter-item correlation coefficient ranged from .082 to .488. Conclusion: Content validity was found to be high, representing the core theme of the construct. The domains (compensatory strategies and rehabilitative techniques) showed good correlation with each other and their item (instructions). The therapeutic exercises manual may be use-able for the patients to eliminate the aspiration and penetration.

Drugs acting at the opioid receptor family are clinically used to treat chronic and acute pain, though they represent the second line of treatment behind GABA analogs, antidepressants and SSRI’s. Within the opioid family mu and kappa opioid receptor are commonly targeted. However, activation of the mu opioid receptor has side effects of constipation, tolerance, dependence, euphoria, and respiratory depression; activation of the kappa opioid receptor leads to dysphoria and sedation. The side effects of mu opioid receptor activation have led to mu receptor drugs being widely abused with great overdose risk. For these reasons, newer safer opioid analgesics are in high demand. For many years a focus within the opioid field was finding drugs that activated the G protein pathway at mu opioid receptor, without activating the β-arrestin pathway, known as biased agonism. Recent advances have shown that this may not be the way forward to develop safer analgesics at mu opioid receptor, though there is still some promise at the kappa opioid receptor. Here we discuss recent novel approaches to develop safer opioid drugs including efficacy vs bias and fine-tuning receptor activation by targeting sub-pockets in the orthosteric site, we explore recent works on the structural basis of bias, and we put forward the suggestion that Gα subtype selectivity may be an exciting new area of interest.

Objectives Amyloid light chain (AL)-κ and AL-λ share common histopathologic changes; however, the potential difference in clinical manifestations, histologic findings, and clinical significance between the 2 subtypes remain unclear. Methods In a retrospective study, 94 kidney biopsies for AL amyloidosis were evaluated using the composite scarring injury score (CSIS) and amyloid score (AS). Results were then compared between AL-κ and AL-λ. Results Comparing AS and CSIS between AL-κ and AL-λ, the AS was significantly higher in AL-κ than in AL-λ, with 2 components of AS (capillary wall and vascular amyloid) scoring higher in AL-κ than in AL-λ, while mesangial and interstitial ASs were similar in the 2 cohorts. In addition, the proportion of periodic acid–Schiff strong-staining amyloid in AL-κ was markedly higher than in AL-λ. There was no significant difference in CSIS and its components between the 2 subtypes of AL amyloidosis. Conclusions Overall, AL-κ presents with higher serum creatinine and a higher AS score than AL-λ at biopsy, which may indicate a worse prognosis and be an important reference for clinical management. [ABSTRACT FROM AUTHOR]

The quantification of earthquake-generated site-specific ground motions is necessary for accurate and reliable seismic hazard assessment for critical structures. To this aim, empirical and numerical approaches are typically used in order to characterize the site response at the target site. This is not straightforward in low-seismicity regions and even more challenging when the target structure is located at great depth. This article, focusing on a practical application for an underground radioactive waste repository project to be located in the eastern part of the Paris Basin (France), presents and discusses the results and the faced challenges in the characterization of the site transfer function (TF) from surface to several depths as well as when assessing the applicability of the ergodic site terms from empirical ground motion models to the target site. We first present the data collected in the last years at the project site and the empirical TFs between the surface and two locations at depth (–490 m and –445 m). The empirical transfer function is robust in the frequency range 0.5–10 Hz and less reliable above 10 Hz due to the reduced number of usable recordings. A good consistency is found with the numerical transfer function based on a 1D soil model derived from local boreholes data. A transfer function based on noise recordings is also computed and compared to the earthquake-based one showing a good agreement of the horizontal components. These results clearly open several perspectives on the potential use of ambient noise data and numerical modelling in order to quantify the site response at any point of the underground project layout. Then, we investigate the site-specific high-frequency decay parameter κ 0 using the available earthquake recordings at the surface. The estimates of κ 0 obtained combining both acceleration- and displacement-based approaches are affected by large uncertainties owing mainly to the lack of data at short distances (< than 100 km). Nonetheless, a range of κ 0 values having a central κ 0 =0.042 s and lower and upper bounds of 0.02 s and 0.058 s is proposed and V s - κ 0 adjustment factors are calculated using the IRVT approach (Al Atik 2014 BSSA 104:336–346) for few example cases. Such adjustment factors together with the empirical TFs and related uncertainties can be used to remove the ergodic assumption on the site term of GMMs in order to improve classical ergodic seismic hazard assessment for structures at surface and at depth. [ABSTRACT FROM AUTHOR]

Purpose : To assess how eye axes and multifocal intraocular lens (MIOL) centration may impact the light distortion index (LDI) and ocular scatter index (OSI). Methods: Fifty-eight subjects implanted with the trifocal MIOL Q-Flex M 640PM or Liberty 677MY (Medicontur) were included in this retrospective analysis. The following variables were collected with the Pentacam Wave (Oculus) considering the vertex normal as the coordinates center: chord-mu to the center of the pupil, chord-alpha to the geometrical center of the cornea, and chord-MIOL to the center of the diffractive ring. These measurements were correlated with OSI (HD Analyzer, Visiometrics) and LDI (light distortion analyzer, CEORLab). Results: Chord-MIOL centroid was 0.12 mm at 62°, chord-mu was 0.09 mm at 174°, and chord-alpha was 0.38 mm at 188°. A relationship was found between OSI and LDI, rho = 0.58, p < 0.0005). No relationships were found between chord-mu or chord-alpha and the LDI or OSI, neither for the total magnitude, nor the decomposition in orthogonal components (p > 0.05). The LDI was significantly correlated with the temporal centration of the MIOL versus the vertex normal (rho = 0.32, p = 0.02). Conclusions: As opposed to what has been previously described, the temporal centration of the MIOL was related to a decrease in the LDI. Future studies with extreme values of the included variables are required to establish cut-offs for considering these variables as exclusion criteria in the implantation of a MIOL. [ABSTRACT FROM AUTHOR]

Background: Determination of free light chains is used increasingly for patients with multiple myeloma and other plasma cell dyscrasias. The aim of the present study was to define reference intervals for free kappa and lambda chains and kappa/lambda ratio in lithium heparin plasma and compare the test results with cystatin C based estimated glomerular filtration rate. Methods: Free kappa and lambda chains were measured in Li-heparin plasma from 222 healthy blood donors using free light chain reagents and a BNII nephelometer from Siemens Diagnostics. Results: Calculated reference intervals for kappa chain, free was 4.73 mg/L (90% confidence interval 4.00 - 5.45) - 22.66 mg/L (20.33 - 24.98), for lambda chain, free was 4.33 mg/L (3.70 - 4.95) - 29.28 mg/L (26.96 - 31.59), and for Kappa/Lambda Chain ratio 0.59 (0.56 - 0.62) - 1.46 (1.37 - 1.56). There was no need for gender or age specific reference intervals. Cystatin C based estimated glomerular filtration rate had a significant effect on the levels of free light chains. Conclusions: The study presents reference intervals for plasma free light chains and compared results of estimated glomerular filtration rate with free light chains of kappa and lambda. [ABSTRACT FROM AUTHOR]

ÖZ: Bu araştırmada klasik kuramlara göre puanlayıcılar arası uyum katsayılarını karşılaştırmak amaçlanmıştır. Farklı ölçekleme türlerine göre elde edilen katsayılar üzerinden hesaplanan değerler arasındaki farka odaklanılmış ve ölçekleme türüne karar vermenin önemi ortaya konmuştur. Puanlanan ve puanlayıcı sayısının değişmesinin değerleri etkileyip etkilemediğine bakılmış ve genellenebilirlik kuramının optimizasyon analizi kullanılarak puanlayıcılar arası uyum için kullanılacak en uygun örneklem büyüklüğü hesaplanmıştır. Araştırmada toplamda 35 çocuğa Bender Görsel Motor Gestalt II testinin yaş gruplarında ortak olan 9 kopyalama kartı uygulanmış ve alınan ölçümler toplamda 8 puanlayıcı tarafından birbirlerine kör olarak değerlendirilmiştir. Sonuçlara göre en yüksek uyum değeri sınıf içi korelasyon katsayısında hesaplanmış ve bu değeri sırasıyla Krippendorff alfa, Fleiss kappa ve Cohen kappa takip etmiştir. Hem puanlanan hem de puanlayıcı sayısı azaldıkça uyum değerlerinin düşme eğiliminde olduğu tespit edilmiştir. Öte yandan kartların zorluk düzeyinin anlamlı bir etkisi olmadığı saptanmıştır. Genellenebilirlik katsayılarının yüksek çıkması testin puanlayıcılar tarafından güvenilir şekilde puanlandığını göstermiştir. Optimizasyon analizi incelendiğinde bu test için en uygun örneklem büyüklüğünün 50 olduğu görülmüştür. Katılımcı sayısının 50’den fazla olması ise uyumu arttırmamıştır. ABSTRACT: In this study, it was aimed to compare the coefficients of interrater agreement according to classical statistic theories. The difference between the calculated agreement coefficients according to different scaling types has been focused and the importance of deciding on the scaling type has been revealed. It was examined whether the change in the number of raters and rateds affected the values, and the most appropriate sample size to be used for the interrater agreement was calculated by using the optimization analysis of the generalizability theory. In the study, 9 cards of the Bender-Gestalt motor skill test, which can be seen by everyone, were applied to 35 children in total, and the measurements were evaluated by 8 raters blindly to each other. Accordingly, the highest agreement value was calculated in the intra-class correlation coefficient and this value was followed by Krippendorff alpha, Fleiss kappa and Cohen kappa, respectively. It has been determined that as both the number of rateds and raters decrease, the agreement values tend to decrease. On the other hand, it was determined that the difficulty level of the cards did not have a significant effect. The high generalizability coefficients showed that the test was reliably scored by the raters. When the optimization analysis was examined, it was seen that the most suitable sample size for this test was 50. Having more than 50 participants did not increase agreement.

Pain is complex and is a unique experience for individuals in that no two people will have exactly the same physiological and emotional response to the same noxious stimulus or injury. Pain is composed of two essential processes: a sensory component that allows for discrimination of the intensity and location of a painful stimulus and an emotional component that underlies the affective, motivational, unpleasant, and aversive response to a painful stimulus. Kappa opioid receptor (KOR) activation in the periphery and throughout the neuroaxis modulates both of these components of the pain experience. In this chapter we focus on recent findings that KORs contribute to the emotional, aversive nature of chronic pain, including how expression in the limbic circuitry contributes to anhedonic states and components of opioid misuse disorder. While the primary focus is on preclinical pain models, we also highlight clinical or human research where there is strong evidence for KOR involvement in negative affective states associated with chronic pain and opioid misuse.

The strong ground motions at a particular site played an important part from the point of view of seismic hazard estimation. For this purpose, various methods/techniques are present in the seismological literature. A hybrid technique, based on the composite source model and envelope technique has been modified in the present research to simulate the ground motions for an earthquake at the surface level. For modifying the technique, the effects of high-frequency parameter kappa (κ) and empirical transfer functions have been included in the hybrid method. The reliability of the modified hybrid technique has been confirmed by modelling the empirical accelerograms of the 2011 Sikkim earthquake (M 6.9). The empirical transfer functions have been computed by the use of observed data of the earthquake. The causative fault of the earthquake has been identified by simulating the accelerograms considering both the nodal planes separately. The essential parameters of the strong ground motions are peak ground acceleration (PGA), duration of the accelerograms, response and Fourier spectrum of simulated accelerograms have been found consistent with recorded ones. Based on the comparison between simulated and observed accelerograms, the regression relation for attenuation of PGA and quality factor (Q) for the region have been identified. The hybrid technique modified here is capable of generating realistic simulated accelerograms for future similar earthquakes in the region. These findings might be obliging in preparing seismic-scenario hazard maps of the region required in the mitigation plans. Article Highlights: Hybrid Technique is modified by introducing the high-frequency parameter (kappa) and empirical transfer function. Modified Hybrid technique is used to model the empirical accelerograms for 2011, Sikkim Earthquake (Mw 6.9). Constrained the attenuation relation of PGA and frequency-dependent Q-relation for the Sikkim Himalaya region. [ABSTRACT FROM AUTHOR]

The New Coimbra Method is the most recently proposed standardized method to assess entheseal changes (EC). However, the method's developers acknowledge the inadequacy of their guidelines and state that those who will use the method need in‐person training from them. This study aims to determine the applicability of the method's guideline by testing the interobserver agreement (IOA) with observers who were not trained by the developers. The second objective of this study is to apply the New Coimbra Method to a relatively small archeological sample, in this case a Bronze Age population from Kültepe‐Kanesh, Türkiye. Four observers (the authors) scored EC in three entheses of the right upper limb of 52 adults. IOA was analyzed via Fleiss' kappa (FK) and percentage of agreement (PA) tests. FK test results indicate moderate overall agreement (0.458), while PA implies significantly high agreement (95%). The results of the FK and PA tests contradict each other due to the known limitations of the latter. However, FK values among features vary broadly; some of the features indicate substantial agreement and surpass the required benchmark, while the rest remains moderate or lower. The features that revealed substantial agreement indicate the sufficiency of the method's guidelines. However, the guidelines for the other features appear to be inadequate. Further revision of the guidelines could make the method more applicable for all researchers with no requirement of in‐person training. [ABSTRACT FROM AUTHOR]

Interrater reliability of Modic changes is subject to variables which affect consistency in reporting. Given the importance of Modic change identification for basivertebral nerve ablation (BVNA) candidacy, interrater reliability for this specific cohort has not yet been reported. Twenty lumbar magnetic resonance images of potential basivertebral nerve candidates were independently reviewed by two neuroradiologists and two interventional spine physiatrists for the presence and characterization of Modic changes. The kappa value of their agreement on the presence of Modic changes was 0.52 (95% confidence interval [CI] 0.37–0.67), whereas agreement on the type of Modic change was 0.51 (95% CI 0.37–0.65). Using an alternative methodology for measuring interrater reliability (Gwet's AC1) yielded the identification of the presence of Modic changes at AC1 0.51 (95% CI 0.36–0.66), whereas agreement on the type of Modic change was AC1 0.75 (95% CI 0.66–0.83). While less common, AC1 may be preferred in the appropriate cohort to kappa as it mitigates some of the pitfalls to which kappa values may be victim. Ultimately, our results are in‐line with previous reports of interrater reliability results for Modic changes in other cohorts and should serve to caution those who perform BVNA regarding interrater agreement of the imaging crux of the procedure. [ABSTRACT FROM AUTHOR]

This research aimed to assess the clinical usefulness of serum kappa (κ) and lambda (λ) free light chains (FLCs) in patients with bladder cancer (BC). One hundred samples were collected and analysed from healthy volunteers (C) and bladder cancer patients. Cancer patients were divided into two subgroups: low-grade (LG) and high-grade cancer (HG). Concentrations of FLCs, CEA, CA19-9, creatinine and urea were measured per manufacturers' guidelines. The concentrations of κ and λ FLCs and CEA were significantly higher in BC patients in comparison to the control group. Moreover, the concentrations of κ and λ FLCs and CEA were significantly higher in both low-grade as well as high-grade cancer in comparison to the controls. The levels of κ and λ FLCs differed between tumour grades, with patients presenting higher concentrations in high-grade compared to low-grade cancer. In the total study group, κFLC correlated with λFLC, the κ:λ ratio, CRP, CEA, CA19-9, creatinine and urea. There was also a correlation between λFLC and κFLC, CRP, CEA, creatinine and urea. The λFLC showed a higher ability (sensitivity and PPV) to detect bladder cancer in comparison to κFLC and CEA. In addition, λFLC had a higher ability to exclude BC (specificity and NPV) than κFLC and CEA. λFLC also showed the highest accuracy in the detection of bladder cancer. In conclusion, the revealed differences in the concentrations of both κ and λ FLCs suggest their potential participation in bladder cancer development. Increased concentrations of free light chains in bladder cancer patients and the association with the tumour grade suggest that κ and λ FLC measurements may be useful in the diagnosis and prognosis of bladder cancer. This is the first research that evaluates the concentration of FLCs in bladder cancer, so further studies are necessary to confirm their usefulness as tumour markers of this malignancy. [ABSTRACT FROM AUTHOR]

Nalfurafine, a moderately selective kappa opioid receptor (KOR) agonist, is used in Japan for treatment of itch without causing dysphoria or psychotomimesis. Here we characterized the pharmacology of compound 42B, a 3-dehydroxy analogue of nalfurafine and compared with that of nalfurafine. Nalfurafine and 42B acted as full KOR agonists and partial μ opioid receptor (MOR) agonists, but 42B showed much lower potency for both receptors and lower KOR/MOR selectivity, different from previous reports. Molecular modeling revealed that water-mediated hydrogen-bond formation between 3-OH of nalfurafine and KOR accounted for its higher KOR potency than 42B. The higher potency of both at KOR over MOR may be due to hydrogen-bond formation between nonconserved Y7.35 of KOR and their carbonyl groups. Both showed modest G protein signaling biases. In mice, like nalfurafine, 42B produced antinociceptive and antiscratch effects and did not cause conditioned place aversion (CPA) in the effective dose ranges. Unlike nalfurafine, 42B caused motor incoordination and hypolocomotion. As both agonists showed G protein biases, yet produced different effects on locomotor activity and motor incoordination, the findings and those in the literature suggest caution in correlating in vitro biochemical data with in vivo behavior effects. The factors contributing to the disconnect, including pharmacodynamic and pharmacokinetic issues, are discussed. In addition, our results suggest that among the KOR-induced adverse behaviors, CPA can be separated from motor incoordination and hypolocomotion.

ObjectiveTo determine the interobserver agreement of history and physical examination findings in children undergoing evaluation in the emergency department (ED) for headaches.Study designWe conducted a prospective, cross-sectional study of children aged 2-17 years evaluated at 3 tertiary-care pediatric EDs for non-traumatic headaches. Two clinicians independently completed a standardized assessment of each child and documented the presence or absence of history and physical examination variables. Unweighted κ statistics were determined for 68 history and 24 physical examination variables.ResultsWe analyzed 191 paired observations; median age was 12 years, with 19 (9.9%) children younger than 7 years. Interrater reliability was at least moderate (κ ≥ 0.41) for 41 (60.3%) patient history variables. Eleven (61.1%) of 18 physical examination variables for which κ statistics could be calculated had a κ that was at least moderate.ConclusionsA substantial number of history and physical examination findings demonstrated at least moderate κ statistic values when assessed in children with headaches in the ED. These variables may be generalizable across different types of clinicians for evaluation of children with headaches. If also found to predict the presence or absence of emergent intracranial abnormalities, the more reliable clinical findings may be helpful in the development of clinical prediction rules or risk stratification models that could be used across settings for children with headaches.

The National Institute of Mental Health (NIMH) 'fast-fail' approach seeks to improve too-often-misleading early-phase drug development methods by incorporating biomarker-based proof-of-mechanism (POM) testing in phase 2a. This first comprehensive application of the fast-fail approach evaluated the potential of κ-opioid receptor (KOR) antagonism for treating anhedonia with a POM study determining whether robust target engagement favorably impacts the brain circuitry hypothesized to mediate clinical effects. Here we report the results from a multicenter, 8-week, double-blind, placebo-controlled, randomized trial in patients with anhedonia and a mood or anxiety disorder (selective KOR antagonist (JNJ-67953964, 10 mg; n = 45) and placebo (n = 44)). JNJ-67953964 significantly increased functional magnetic resonance imaging (fMRI) ventral striatum activation during reward anticipation (primary outcome) as compared to placebo (baseline-adjusted mean: JNJ-67953964, 0.72 (s.d. = 0.67); placebo, 0.33 (s.d. = 0.68); F(1,86) = 5.58, P

Abstract Background In low-resource countries, interpretation of the transformation zone (TZ) using the classification of the International Federation for Cervical Pathology and Colposcopy (IFCPC), adopted by the World Health Organization, is critical for determining if visual inspection with acetic acid (VIA) screening and thermal ablation treatment are possible. We aim to assess inter- and intra-observer agreement in TZ interpretation. Methods We performed a prospective multi-observer reliability study. One hundred cervical digital images of Human papillomavirus positive women (30–49 years) were consecutively selected from a Cameroonian cervical cancer screening trial. Images of the native cervix and after VIA were obtained. The images were evaluated for the TZ type at two time points (rounds one and two) by five VIA experts from four countries (Côte d’Ivoire, Cameroon, Peru, and Zambia) according to the IFCPC classification (TZ1 = ectocervical fully visible; TZ2 = endocervical fully visible; TZ3 = not fully visible). Intra- and inter-observer agreement were measured by Fleiss’ kappa. Results Overall, 37.0% of images were interpreted as TZ1, 36.4% as TZ2, and 26.6% as TZ3. Global inter-observer reliability indicated fair agreement in both rounds (kappa 0.313 and 0.288). The inter-observer agreement was moderate for TZ1 interpretation (0.460), slight for TZ2 (0.153), and fair for TZ3 (0.329). Intra-observer analysis showed fair agreement for two observers (0.356 and 0.345), moderate agreement for two other (0.562 and 0.549), and one with substantial agreement (0.728). Conclusion Interpretation of the TZ using the IFCPC classification, adopted by the World Health Organization, is critical for determining if VIA screening and thermal ablation treatment are possible. However, the low inter- and intra-observer agreement suggest that the reliability of the referred classification is limited in the context of VIA. It’s integration in treatment recommendations should be used with caution since TZ3 interpretation could lead to an important referral rate for further evaluation. Trial registration Cantonal Ethics Board of Geneva, Switzerland: N°2017–0110. Cameroonian National Ethics Committee for Human Health Research N°2018/07/1083/CE/CNERSH/SP.

The study of land use and land cover change (LULC) is essential for the development of strategies, monitoring and control of the ecosystem. The present study aims to describe the dynamics of land cover and land use, and specially the impact of certain climatic parameters on the distribution of vegetation and land cover. For this study, multi-temporal remote sensing data are used to monitor land cover changes in Morocco, using a set of Landsat images, including Landsat 7 (ETM+), Landsat 5 (TM), and Landsat 8 (OLI), captured during the period 2000-2020, those changes were determined by adopting the maximum likelihood (ML) classification method. The classification results show good accuracy values in the range of 90% (2000), 80% (2007), 82% (2010), 93% (2020). The LU/LC change detection showed a decrease of agricultural and forest areas in the order of 5% between the year 2000 and 2020, and an increase of bare soil of 5% to 6%, and a notable change in urban area from 97.31 ha (0.03%) in 2000 to 2988.2637ha (0.82%) in 2020. The overall results obtained from LULC show that the vegetation cover of the study area has undergone major changes during the study period. In order to monitor the vegetation status, an analysis of the precipitation-vegetation interaction is essential. The normalized difference vegetation index (NDVI) was determined from 2000 to 2020, to identify vegetation categories and quantify the vegetation density in the Lakhdar sub-basin. The obtained NDVI was analyzed using climatic index SPI (Normalized Precipitation Index) based on rainfall data from five stations. The correlation study between NDVI and SPI indices shows a strong linear relation between these two indicators especially while using an annual index SPI12 however, the use of NDVI index based on remote sensing provides a significant result while assessing vegetation. The results of our study can be used for vegetation monitoring and sustainable management of the area, since it is one of the largest basins in the country.

Abstract A 10‐year‐old, entire male, English Springer Spaniel was referred for evaluation of weight loss, polyuria, polydipsia and gastrointestinal tract signs including melena/haematochezia for the previous six months. Results of serum protein electrophoresis, urine analysis, computed tomography of the thorax/abdomen, bone marrow aspiration and core biopsy, and splenic and mesenteric lymph node cytology were consistent with multiple myeloma. Endoscopically obtained gastrointestinal tract biopsies identified marked plasma cell infiltration within the duodenum, ileum and colon; immunohistochemistry showed positive labelling to MUM1 and Lambda confirming clonal plasma cell involvement. The dog entered complete clinical remission seven weeks after starting a melphalan/prednisolone protocol. The dog was euthanised 475 days after starting treatment due to cervical pain and collapse. At the time of euthanasia, blood work was not supportive of a relapse of multiple myeloma. To the authors’ knowledge, this is the first report of multiple myeloma involving the gastrointestinal tract in a dog.