Comprehensive model for predicting toxic equivalents (TEQ) reduction due to dechlorination of polychlorinated dibenzo-p-dioxin and dibenzofurans (PCDD/F congeners).

Remediation-focused predictive tools for polychlorinated dibenzo-p-dioxins (PCDD) and polychlorinated dibenzofurans (PCDF) rely on transformation models to evaluate the reduction in total contaminant load and toxic equivalency (TEQ). In this study, a comprehensive model predicting the profiles of PCDD/F congeners and the associated TEQs was developed. The model employs first-order kinetics to describe the transformation of 256 reactions for 75 PCDD congeners and 421 reactions for 135 PCDF congeners. It integrates the growth of anaerobic microbial guilds using Monod kinetics on hydrogen release compounds and stoichiometric growth for Dehalococcoides sp. The effects of temperature, salinity, pH, and availability of vitamin B12 (a cofactor) were also integrated. The PCDD/F congeners model was used to extract the first-order dechlorination rate constants from a number of pure culture and mixed microbial microcosm studies. Simulations for the transformation of PCDD/F congeners at concentrations representative of the Tittabawassee or Saginaw Rivers and watershed in MI, USA were carried out. For a starting TEQ of 5000 ng per kg dry sediment (ppt), the model predicted a decrease in the overall TEQ to below 2000 ppt after 2.6 years and below 250 ppt after ∼21 years. The developed model may be used for extracting rates from microcosm studies and to evaluate the effect of engineering interventions on TEQ reduction.

Two Acceleration-Layer Configuration Amendment Schemes of Redundant Robot Arms Based on Zhang Neurodynamics Equivalency.

Two innovative acceleration-layer configuration amendment (CA) schemes are proposed to achieve the CA of constrained redundant robot arms. Specifically, by applying the Zhang neurodynamics equivalency (ZNE) method, an acceleration-layer CA performance indicator is derived theoretically. To obtain a unified-layer inequality constraint by transforming from angle-layer and velocity-layer constraints to acceleration-layer constraints, five theorems and three corollaries are theoretically derived and rigorously proved. Then, together with the unified acceleration-layer bound constraint, an enhanced acceleration-layer CA scheme specially considering three-layer time-variant physical limits is proposed, and a simplified acceleration-layer CA scheme considering three-layer time-invariant physical limits is also proposed. The proposed CA schemes are finally formulated in the form of standard quadratic programming and are solved by a projection neurodynamics solver. Moreover, comparative simulative experiments based on a four-link planar arm and a UR3 spatial arm are performed to verify the efficacy and superiority of the proposed CA schemes. At last, physical experiments are conducted on a real Kinova Jaco2 arm to substantiate the practicability of the proposed CA schemes.

Transforming Continuing Professional Development for Healthcare Professionals to Meet National Goals in Saudi Arabia.

The Saudi Commission for Health Specialties (SCFHS), the regulatory agency for health professions in the Kingdom of Saudi Arabia (KSA), sought to evolve the continuing professional development (CPD) ecosystem for the country and to promote the concept of life-long learning for healthcare professionals. SCFHS audited its own CPD accreditation system, reviewed internationally recognised CPD accreditation criteria, adopted a new set of standards, and trained its staff and provider community in their adoption. SCFHS also deployed a range of programmes and grants to support healthcare educators and researchers engaged in CPD. SCFHS recruited and trained new staff and deployed an updated IT system to support system change. The adopted criteria and standards now align with best practices, as outlined by the Accreditation Council for Continuing Medical Education (ACCME) and the International Academy for CPD Accreditation. More than 170 educators have participated in programmes to learn effective CPD pedagogy. The adoption of new standards resulted in 396 providers seeking provider accreditation. The number of CPD accredited activities produced in the KSA and approved by the SCFHS has grown from 1,000 activities in 2002 to 10,500 in 2022. With leadership support, regulatory evolution to align with best practices supports healthcare educators and effectively expands of the diversity and quality of CPD.

A Feasibility Study on Re-establishing the Bioavailability/Bioequivalence Unit of the Department of Pharmacology and Toxicology, College of Medicine-University of the Philippines Manila.

Objectives: The Bioavailability/Bioequivalence Unit (BA/BE Unit) of the Department of Pharmacology and Toxicology, College of Medicine, University of the Philippines Manila which has not been operational since 2012, is due for renewal of its accreditation. To date, there are only three Philippine Food and Drug Administration-accredited laboratories that perform bioequivalence studies in the Philippines. One of the prerequisites of registering specific generic medicines is the conduct of Bioequivalence (BE) studies which are performed to ensure that the generic drug is at par with the innovator drug. Thus, this study aimed to determine the feasibility of re-establishing the BA/BE Unit as a bioequivalence testing center. Methods: The feasibility study done is a qualitative descriptive analysis based on expansive literature review and performance of SWOT analysis within the BA/BE unit. Literatures were selected based on its assessed relevance to the study. The databases checked were PubMed and Google Scholar. The terms used were from the Medical Subject Heading (MeSH) including feasibility studies, therapeutic equivalency, and generic drugs. Literature review was performed on the factors affecting the four types of feasibility studies (market, technical, financial, and organizational). A SWOT analysis of the BA/BE Unit was done through the review of records and documents of previous BE studies and focus group discussion among the BA/BE Unit team members. Results: The BA/BE Unit conducted 24 bioequivalence studies from 2006-2009 and still receives inquiries from drug companies. It implements its QMS throughout the pre-analytical, analytical, and post-analytical stages of the workflow. Its organizational structure consists of qualified professionals with updated GCP and GLP certificates. Because of the adequately equipped facility, lower honoraria for government-employed personnel, and lower expenses for laboratories and in-patient admissions, the cost of conducting a bioequivalence study in the BA/BE Unit will be lower than in other BE centers. Conclusion: Based on the SWOT analysis and market, technical, financial, and organizational considerations, re-establishing the BA/BE Unit as a bioequivalence testing center is feasible.

Dissimilar ferric derisomaltose formulations - In vitro comparisons between an originator and its intended similars.

BACKGROUND: The complex nature of intravenous (IV) iron formulations makes manufacturing and characterising similars challenging. This study examined whether simple in vitro tests can distinguish the high-dose IV iron formulation, Monofer® (ferric derisomaltose [FDI]), from the first intended copies of FDI, Rapifer® (FDI intended similar A [FDIIS-A]) and Tosiron® (FDI intended similar B [FDIIS-B]), approved in India and Pakistan, respectively. Neither intended similar is available in Europe or the United States. METHODS: Iron content, pH, density, non-volatile residue, carbohydrate content, molecular weight distribution, complex robustness (measured using acid hydrolysis half-life [t½]) and free (dialysable) iron content were examined. Mean results from three batches of FDIIS-A were compared with mean values calculated from three batches of Monofer®. Due to product withdrawal, only one batch of FDIIS-B was available for comparison with Monofer®. RESULTS: Iron content was similar for all formulations (∼100 mg/mL). The chromatograms (obtained using gel permeation chromatography) of FDIIS-A and FDIIS-B differed from that of Monofer®. FDIIS-A was substantially less robust than Monofer® (t½: 15 h versus 40.3 h); t½ for FDIIS-B was not tested. Free iron content was substantially higher in FDIIS-A (0.091 % w/v) and FDIIS-B (1.0 % w/v) versus Monofer® (<0.003 % w/v). Where tested, remaining parameters varied between the formulations (insufficient sample quantities prevented all tests being conducted for all intended similars). For all tests, greater inter-batch variability was seen for FDIIS-A versus Monofer®. CONCLUSIONS: Simple in vitro tests demonstrated that, aside from total iron content, the first intended similars of FDI bear little resemblance to their originator drug. It is clear that the efficacy and safety profile of Monofer® cannot be extrapolated to the two intended similars. The results call for increased regulatory scrutiny of intended IV iron similars.

Rodent and broiler feeding studies with maize containing genetically modified event DP-915635-4 show no adverse effects on health or performance.

Several regulatory agencies continue to require animal feeding studies to approve new genetically modified crops despite such studies providing little value in the safety assessment. Feeding studies with maize grain containing event DP-915635-4 (DP915635), a new corn rootworm management trait, were conducted to fulfill that requirement. Diets fed to Crl:CD®(SD) rats for 90 days contained up to 50% ground maize grain from DP915635, non-transgenic control, or non-transgenic reference hybrids (P1197, 6158, and 6365). Ross 708 broilers received phase diets containing up to 67% maize grain from each source for 42 days. Growth performance was compared between animals fed DP915635 and control diets; rats were further evaluated for clinical and neurobehavioral measures, ophthalmology, clinical pathology, organ weights, and gross and microscopic pathology, whereas carcass parts and select organ yields were determined for broilers. Reference group inclusion assisted in determining natural variation influence on observed significant differences between DP915635 and control groups. DP915635 maize grain diet consumption did not affect any measure evaluated in either feeding study. Results demonstrated DP-915635-4 maize grain safety and nutritional equivalency when fed in nutritionally adequate diets, adding to the existing literature confirming the lack of significant effects of feeding grain from genetically modified plants.

Systematic update to the mammalian relative potency estimate database and development of best estimate toxic equivalency factors for dioxin-like compounds.

The World Health Organization (WHO) assesses potential health risks of dioxin-like compounds using Toxic Equivalency Factors (TEFs). This study systematically updated the relative potency (REP) database underlying the 2005 WHO TEFs and applied advanced methods for quantitative integration of study quality and dose-response. Data obtained from fifty-one publications more than doubled the size of the previous REP database (∼1300 datasets). REP quality and relevance for these data was assessed via application of a consensus-based weighting framework. Using Bayesian dose-response modeling, available data were modeled to produce standardized dose/concentration-response Hill curves. Study quality and REP data were synthesized via Bayesian meta-analysis to integrate dose/concentration-response data, author-calculated REPs and benchmark ratios. The output is a prediction of the most likely relationship between each congener and its reference as model-predicted TEF uncertainty distributions, or the 'best estimate TEF' (BE-TEF). The resulting weighted BE-TEFs were similar to the 2005 TEFs, though provide more information to inform selection of TEF values as well as to provide risk assessors and managers with information needed to quantitatively characterize uncertainty around TEF values. Collectively, these efforts produce an updated REP database and an objective, reproducible approach to support development of TEF values based on all available data.

Zhang equivalency of inequation-to-inequation type for constraints of redundant manipulators.

In solving specific problems, physical laws and mathematical theorems directly express the connections between variables with equations/inequations. At times, it could be extremely hard or not viable to solve these equations/inequations directly. The PE (principle of equivalence) is a commonly applied pragmatic method across multiple fields. PE transforms the initial equations/inequations into simplified equivalent equations/inequations that are more manageable to solve, allowing researchers to achieve their objectives. The problem-solving process in many fields benefits from the use of PE. Recently, the ZE (Zhang equivalency) framework has surfaced as a promising approach for addressing time-dependent optimization problems. This ZEF (ZE framework) consolidates constraints at different tiers, demonstrating its capacity for the solving of time-dependent optimization problems. To broaden the application of ZEF in time-dependent optimization problems, specifically in the domain of motion planning for redundant manipulators, the authors systematically investigate the ZEF-I2I (ZEF of the inequation-to-inequation) type. The study concentrates on transforming constraints (i.e., joint constraints and obstacles avoidance depicted in different tiers) into consolidated constraints backed by rigorous mathematical derivations. The effectiveness and applicability of the ZEF-I2I are verified through two optimization motion planning schemes, which consolidate constraints in the velocity-tier and acceleration-tier. Schemes are required to accomplish the goal of repetitive motion planning within constraints. The firstly presented optimization motion planning schemes are then reformulated as two time-dependent quadratic programming problems. Simulative experiments conducted on the basis of a six-joint redundant manipulator confirm the outstanding effectiveness of the firstly presented ZEF-I2I in achieving the goal of motion planning within constraints.

The effect of age on clinical dose equivalency of fentanyl and morphine analgosedation in mechanically ventilated patients: Findings from the ANALGESIC trial.

BACKGROUND: The dose equivalency of fentanyl vs. morphine is widely considered to be approximately 1:100. However, little is known about the effect of age on this ratio when these agents are used as infusions for analgosedation. OBJECTIVES: To assess the impact of age on the clinical dose equivalency of fentanyl and morphine when used as infusions for analgosedation in mechanically ventilated intensive care unit patients. METHODS: We performed a post hoc analysis of the Assessment of Opioid Administration to Lead to Analgesic Effects and Sedation in Intensive Care (ANALGESIC) cluster randomised crossover trial of fentanyl and morphine infusions for analgosedation. Dose and analgosedative clinical equivalency of fentanyl and morphine were assessed by age and by using different body-size descriptors. RESULTS: We studied 663 patients (338 fentanyl, 325 morphine). Median (interquartile range) hourly dose of fentanyl and morphine were 58.1 (40.0-89.2) mcg and 3400 (2200-5000) mcg, respectively. The ratio of total dose of fentanyl:morphine was 1:93 in the 18- to 29-year-old group and 1:25 in the ≥80-year-old group (p = 0.015), respectively, with fentanyl becoming relatively less clinically effective as age increased. This effect was also seen when comparing dosing by different body-size descriptors with the strongest age-related change when using body surface area as body-size descriptor (p = 0.009). CONCLUSION: The analgosedative clinical dose equivalency of fentanyl vs. morphine is heterogeneous when used as infusions for analgosedation, with fentanyl becoming relatively less clinically effective as age increases. This information can help guide prescription of these agents during transition from one agent to the other in critically ill patients.

Predicted versus observed activity of PCB mixtures toward the ryanodine receptor.

Non-dioxin-like polychlorinated biphenyls (NDL PCBs) alter the activity of the ryanodine receptor (RyR), and this activity is linked to developmental neurotoxicity. Most work to date has focused on the activity of single congeners rather than relevant mixtures. The current study assessed the RyR activity of single congeners or binary, tertiary, and complex PCB mixtures. Observed mixture activity was then compared to the expected activity calculated using the concentration addition (CA) model or a RyR-specific neurotoxic equivalency scheme (rNEQ). The predictions of the CA model were consistent with the observed activity of binary mixtures at the lower portion of the concentration-response curve, supporting the additivity of RyR1 active PCBs. Findings also show that minimally active congeners can compete for the RyR1 binding site, and congeners that do not activate the RyR1 do not interfere with the activity of a full agonist. Complex PCB mixtures that mimic PCB profiles detected in indoor air, fish tissue, and the serum of mothers and children activated the RyR1 and displayed similar efficacy and potency regardless of varying congener profiles. Neither the CA model nor the rNEQ perfectly predicted the observed activity of complex mixtures, but predictions were often within one magnitude of change from the observed response. Importantly, PCB mixtures approximating profiles found in environmental samples or human serum displayed RyR1 activity at concentrations reported in published research. The work presented will aid in the development of risk assessment platforms for NDL PCBs and similar compounds toward RyR1 activation and related neurotoxicity.

Hegemonía en el pluralismo médico: articulaciones y relaciones en la atención, un estudio de caso / Hegemony in medical pluralism: articulations and relationships in care, a case study / Hegemonia no pluralismo médico: articulações e relações no atendimento, um estudo de caso

Este estudio tiene como objetivo describir y analizar el pluralismo médico y el tipo de relaciones de hegemonía-subalternidad entre diversas formas o saberes de atención, que se desarrollaron en el itinerario terapéutico de una padeciente de glaucoma, para mostrar el proceso articulatorio y transaccional entre distintos recursos terapéuticos, así como comprender qué elementos estructurales configuraron el itinerario y la elección terapéutica. La investigación es cualitativa, un estudio de caso en el cual se utilizó el enfoque narrativo. Para la reconstrucción de la narrativa se realizó una entrevista semiestructurada, dirigida por una guía temática previamente determinada por un conjunto de categorías apriorísticas, para posteriormente transcribir la entrevista y realizar un proceso de triangulación hermenéutica. Los resultados mostraron, en este caso, que la hegemonía en el pluralismo médico se constituyó mediante relaciones de equivalencia, así, la padeciente sustituyó el uso de medicamentos farmacológicos por terapias de medicina alternativa, no obstante, el proceso relacional de equivalencia se desarrolló en un contexto de significación biomédica, en el cual tratar o controlar la presión intraocular fue la premisa del remplazo. Asimismo, los procesos que desencadenaron la presencia de relaciones hegemónicas se constituyeron por diversos factores sociales, culturales y económicos como el desempleo, la seguridad social y el género, que desempeñaron un papel fundamental durante la búsqueda de la atención y del cuidado.

This study aims to describe and analyze the medical pluralism and the type of hegemony-subordination relation between forms of care or knowledge in the treatment of a patient with glaucoma to show the articulatory and transactional process between several therapeutic resources and understand which structural elements shaped the treatment itinerary and option. This is a qualitative research that used a narrative case study. To reconstruct the narrative, a semi-structured interview was conducted based on a thematic script previously established by a set of a priori categories to later transcribe the data and perform hermeneutic triangulation. Results showed that the hegemony in medical pluralism was based on equivalence relations, so that the patient replaced the use of pharmacological drugs with alternative medicine treatments. However, the relational process of equivalence developed itself in a context of biomedical significance, in which the treatment or control of intraocular pressure configured the substitution premise. Thus, the processes that triggered the hegemonic relations were constituted by various social, cultural, and economic factors such as unemployment, social security, and gender, which played a fundamental role during the search for care.

Este estudo visa descrever e analisar o pluralismo médico e o tipo de relação de hegemonia-subalternidade entre diversas formas de atendimento ou conhecimentos, que ocorreram no tratamento de um paciente com glaucoma, com a finalidade de mostrar o processo articulatório e transacional entre diferentes recursos terapêuticos, bem como entender quais elementos estruturais moldaram o itinerário e a opção de tratamento. Trata-se de uma pesquisa qualitativa, que utilizou um estudo de caso com abordagem narrativa. Para a reconstrução da narrativa, foi realizada uma entrevista semiestruturada, com base em um roteiro temático previamente estabelecido por um conjunto de categorias a priori, para posteriormente transcrever os dados e realizar a triangulação hermenêutica. Os resultados mostraram que a hegemonia no pluralismo médico esteve baseada em relações de equivalência, de modo que o paciente substituiu o uso de medicamentos farmacológicos por tratamentos da medicina alternativa; no entanto, o processo relacional de equivalência desenvolveu-se em um contexto de significância biomédica, na qual o tratamento ou controle da pressão intraocular foi a premissa para a substituição. Desse modo, os processos que desencadearam a presença de relações hegemônicas foram constituídos por fatores sociais, culturais e econômicos diversos como desemprego, previdência social e gênero, os quais tiveram papel fundamental durante a busca por atendimento e cuidado.

Novel antibody competition binding assay identifies distinct serological profiles associated with protection.

Introduction: Pre-erythrocytic malaria vaccines hold the promise of inducing sterile protection thereby preventing the morbidity and mortality associated with Plasmodium infection. The main surface antigen of P. falciparum sporozoites, i.e., the circumsporozoite protein (CSP), has been extensively explored as a target of such vaccines with significant success in recent years. Systematic adjuvant selection, refinements of the immunization regimen, and physical properties of the antigen may all contribute to the potential of increasing the efficacy of CSP-based vaccines. Protection appears to be dependent in large part on CSP antibodies. However due to a knowledge gap related to the exact correlates of immunity, there is a critical need to improve our ability to down select candidates preclinically before entering clinical trials including with controlled human malaria infections (CHMI). Methods: We developed a novel multiplex competition assay based on well-characterized monoclonal antibodies (mAbs) that target crucial epitopes across the CSP molecule. This new tool assesses both, quality and epitope-specific concentrations of vaccine-induced antibodies by measuring their equivalency with a panel of well-characterized, CSP-epitope-specific mAbs. Results: Applying this method to RTS,S-immune sera from a CHMI trial demonstrated a quantitative epitope-specificity profile of antibody responses that can differentiate between protected vs. nonprotected individuals. Aligning vaccine efficacy with quantitation of the epitope fine specificity results of this equivalency assay reveals the importance of epitope specificity. Discussion: The newly developed serological equivalence assay will inform future vaccine design and possibly even adjuvant selection. This methodology can be adapted to other antigens and disease models, when a panel of relevant mAbs exists, and could offer a unique tool for comparing and down-selecting vaccine formulations.

An Assessment of the Public's Perceptions of Radiation Exposure and Risk Associated With Dental Radiographs: A Cross-Sectional Study.

BACKGROUND: Ionizing radiation exposure is an ever-present part of the dental diagnostic process. A public concern often exists due to the misunderstanding of the stochastic effects of dental X-rays. This information can be difficult to explain to the patient since many patients are apprehensive about the subject matter. OBJECTIVE: This article aims to assess the public's knowledge of radiation exposure and estimate the general concern or apprehension about these diagnostic imaging modalities in an effort to understand and therefore ensure patient reassurance during treatment. METHOD: A questionnaire was conducted asking adults between the ages of 18 to 74 in Jeddah, Saudi Arabia questions pertaining to radiation risk. RESULTS:  There were 105 respondents; 21.9% showed concerns toward dental imaging, while 20% were skeptical. approximately 74% of respondents believed there was a limit to the amount of radiation exposure a patient could receive for diagnostic purposes, while only eight percent correctly identified that there was no set limit. Only 21.9% knew that a breastfeeding mother could have dental X-rays if need be; 33.3% understood that ionizing radiation from an intra-oral dental X-ray caused less exposure than natural background radiation from a return flight from Jeddah to Dammam.  Conclusions: Patients are not aware of ionizing radiation exposure equivalencies between different imaging modalities. A more effective approach to convey exposure risk would be relating the radiation doses to natural background radiation as comparators.

Generation of traffic input for flexible pavement design.

Layered elastic theory (LET) was performed by Burmister. It helped to build mechanistic - empirical (M-E) pavement design. In this study, three different approaches were used to predict Cumulative Equivalent single axle load (C-ESAL) over the design period. Two were based on M-E and one was empirical. In each of these cases, standard axle loads were used as well as weight limits and vehicle classification, according to their axle configurations (single, tandem, tridem). Traffic data came from annual traffic census campaigns over the past ten years. Gross vehicle weight (GVW) and axle weight (AW) data came from a fixed weighing station performed during 31 days in 2020. Two road axis were considered: One having a weighing station (reference road) and one under technical studies (specific road). Traffic road data were used to perform regression analyses and predictions. AW and GVW helped to calculate Axle load equivalency factors (ALEF) and Truck equivalency factors (TEF) on the reference road. These values were projected on the specific road. Frequency distribution, gross vehicle weight distribution, axle load distribution of heavy vehicles are applied on the reference road. We performed overload AW and overload GVW analyses. Comparisons were done for the three approaches and an evaluation of technical studies was proposed, including traffic and AW monitoring and management systems. This work came as a basis for the transposition of M-E calculation of traffic inputs, more accurate and used over the passed fifty years, in Higher Income countries, called AASHTO method for USA, LCPC-SETRA method for France, to Cameroon and Sub-sahara African countries, that have been using empirical generation of traffic inputs over the same period, called CEBTP method.

Second International Consensus Study of Antipsychotic Dosing (ICSAD-2).

BACKGROUND: Expert consensus-based clinically equivalent dose estimates and dosing recommendations can provide valuable support for the use of drugs for psychosis in clinical practice and research. AIMS: This second International Consensus Study of Antipsychotic Dosing provides dosing equivalencies and recommendations for newer drugs for psychosis and previously reported drugs with low consensus. METHODS: We used a two-step Delphi survey process to establish and update consensus with a broad, international sample of clinical and research experts regarding 26 drug formulations to obtain dosing recommendations (start, target range, and maximum) and estimates of clinically equivalent doses for the treatment of schizophrenia. Reference agents for equivalent dose estimates were oral olanzapine 20 mg/day for 15 oral and 7 long-acting injectable (LAI) agents and intramuscular haloperidol 5 mg for 4 short-acting injectable (SAI) agents. We also provide a contemporary list of equivalency estimates and dosing recommendations for a total of 44 oral, 16 LAI, and 14 SAI drugs for psychosis. RESULTS: Survey participants (N = 72) from 24 countries provided equivalency estimates and dosing recommendations for oral, LAI, and SAI formulations. Consensus improved from survey stages I to II. The final consensus was highest for LAI formulations, intermediate for oral agents, and lowest for SAI formulations of drugs for psychosis. CONCLUSIONS: As randomized, controlled, fixed, multiple-dose trials to optimize the dosing of drugs for psychosis remain rare, expert consensus remains a useful alternative for estimating clinical dosing equivalents. The present findings can support clinical practice, guideline development, and research design and interpretation involving drugs for psychosis.

Systems that evaluate international equivalency in health-related professions: a scoping review with a focus on Canada.

Health workforce planning has become a significant global problem considering there are estimates of an 18 million healthcare provider shortfall by 2030. There are two mechanisms to address healthcare worker shortages: (1) domestic education of those professions and (2) integration of internationally educated health professionals. Integration of internationally educated health professionals into the Canadian healthcare system requires: (1) reductions in systemic and administrative barriers and (2) development, testing, and implementation of credential equivalency recognition systems. The goal of this scoping review was to identify systems that are employed to determine credential equivalency, with a focus on Canada. The scoping review was carried by employing: (1) a systematic literature search (9) and (2) a website and grey literature Google search of professional governing bodies from a selection of medical/allied healthcare professions, but also other non-medical professions, such as law, engineering and accounting. Seven databases were searched to identify relevant sources: MEDLINE, CINAHL Plus with Full Text, PsycINFO, SPORT Discus, Academic Search Complete, Business Source Complete, and SCOPUS. The search strategy combined keyword, text terms, and medical subject headings (MeSH) and was carried out with the help of a health sciences librarian. Seven articles were included in the final manuscript review from the following professions: nursing; psychology; engineering; pharmacy; and multiple health professions. Twenty-four health-related professional governing body websites were hand searched to determine systems to evaluate international equivalency. There were many systems employed to determine equivalency, but there were no systems that were automated or that employed machine-learning or artificial intelligence to guide the evaluation process.

Predicted Versus Observed Activity of PCB Mixtures Toward the Ryanodine Receptor.

Non-dioxin-like polychlorinated biphenyls (NDL PCBs) alter the activity of the ryanodine receptor (RyR), and this activity is linked to developmental neurotoxicity. Most work to date has focused on the activity of single congeners rather than relevant mixtures. The current study assessed the RyR activity of single congeners or binary, tertiary, and complex PCB mixtures. Observed mixture activity was then compared to the expected activity calculated using the concentration addition (CA) model or a RyR-specific neurotoxic equivalency scheme (rNEQ). The predictions of the CA model were consistent with the observed activity of binary mixtures at the lower portion of the concentration-response curve, supporting the additivity of RyR1 active PCBs. Findings also show that minimally active congeners can compete for the RyR1 binding site, and congeners that do not activate the RyR1 do not interfere with the activity of a full agonist. Complex PCB mixtures that mimic PCB profiles detected in indoor air, fish tissue, and the serum of mothers and children activated the RyR1 and displayed similar efficacy and potency regardless of varying congener profiles. Neither the CA model nor the rNEQ perfectly predicted the observed activity of complex mixtures, but predictions were often within one magnitude of change from the observed response. Importantly, PCB mixtures approximating profiles found in environmental samples or human serum displayed RyR1 activity at concentrations reported in published research. The work presented will aid in the development of risk assessment platforms for NDL PCBs, and similar compounds, towards RyR1 activation and related neurotoxicity.

Development of an analytical method for indoor polycyclic aromatic hydrocarbons and their halogenated derivatives by using thermal separation probe coupled to gas chromatography-tandem mass spectrometry.

Polycyclic aromatic hydrocarbons (PAHs) and their halogenated derivatives (XPAHs) have been a concern because of their high toxicity. Monitoring indoor PAHs and XPAHs concentrations is important for risk assessment because humans typically spend >90 % of their time indoors. However, the background levels of indoor PAHs and XPAHs concentrations are unknown because of the low sensitivity of conventional analytical methods. In this study, we developed a highly sensitive analytical method using a thermal separation probe (TSP) coupled to a gas chromatograph with a triple quadrupole mass spectrometer method for 26 PAHs and 40 XPAHs. The method quantification limit (MQL) values of the TSP method were 1.1 (3,8-dichlorofluoranthene)-906 (dibenzo[a,e]pyrene) times lower than those of the conventional method. The regression line comparing the TSP and conventional methods was y = (0.944 ± 0.0401)x, which was in good agreement. These results demonstrate that the TSP method can be applied to indoor air analysis. The total concentrations of PAHs and XPAHs were 944 and 73.5 pg m-3 for the house and 735 and 0.924 pg m-3 in the office, respectively. Among the detected compounds, 13 PAHs and XPAHs could not be detected using conventional methods because of their high MQL values. The composition of total toxicity equivalency values in the house was dominated by dibenzo[a,i]pyrene (DBaiP: 43.2 %) and dibenzo[a,h]pyrene (DBahP: 27.1 %), which could not be detected using the conventional method. Therefore, the TSP method can improve the risk assessment of indoor PAHs and XPAHs.

Evaluation of Toxicity Equivalency Factors of Tetrodotoxin Analogues with a Neuro-2a Cell-Based Assay and Application to Puffer Fish from Greece.

Tetrodotoxin (TTX) is a potent marine neurotoxin involved in poisoning cases, especially through the consumption of puffer fish. Knowledge of the toxicity equivalency factors (TEFs) of TTX analogues is crucial in monitoring programs to estimate the toxicity of samples analyzed with instrumental analysis methods. In this work, TTX analogues were isolated from the liver of a Lagocephalus sceleratus individual caught on South Crete coasts. A cell-based assay (CBA) for TTXs was optimized and applied to the establishment of the TEFs of 5,11-dideoxyTTX, 11-norTTX-6(S)-ol, 11-deoxyTTX and 5,6,11-trideoxyTTX. Results showed that all TTX analogues were less toxic than the parent TTX, their TEFs being in the range of 0.75-0.011. Then, different tissues of three Lagocephalus sceleratus individuals were analyzed with CBA and liquid chromatography-tandem mass spectrometry (LC-MS/MS). The obtained TEFs were applied to the TTX analogues' concentrations obtained by LC-MS/MS analysis, providing an indication of the overall toxicity of the sample. Information about the TEFs of TTX analogues is valuable for food safety control, allowing the estimation of the risk of fish products to consumers.

Reasoning and Logical Proofs of the Fundamental Laws: "No Hope" for the Challengers of the Second Law of Thermodynamics.

This comprehensive treatise is written for the special occasion of the author's 70th birthday. It presents his lifelong endeavors and reflections with original reasoning and re-interpretations of the most critical and sometimes misleading issues in thermodynamics-since now, we have the advantage to look at the historical developments more comprehensively and objectively than the pioneers. Starting from Carnot (grand-father of thermodynamics to become) to Kelvin and Clausius (fathers of thermodynamics), and other followers, the most relevant issues are critically examined and put in historical and contemporary perspective. From the original reasoning of generalized "energy forcing and displacement" to the logical proofs of several fundamental laws, to the ubiquity of thermal motion and heat, and the indestructibility of entropy, including the new concept of "thermal roughness" and "inevitability of dissipative irreversibility," to dissecting "Carnot true reversible-equivalency" and the critical concept of "thermal-transformer," limited by the newly generalized "Carnot-Clausius heat-work reversible-equivalency (CCHWRE)," regarding the inter-complementarity of heat and work, and to demonstrating "No Hope" for the "Challengers" of the Second Law of thermodynamics, among others, are offered. It is hoped that the novel contributions presented here will enlighten better comprehension and resolve some of the fundamental issues, as well as promote collaboration and future progress.