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Abstract Our study assessed DATASUS as a potential source for pharmacoepidemiologic studies in rheumatoid arthritis (RA) in the Brazilian population focusing on treatment patterns and determinants of initiating or switching to a novel therapy. This was a descriptive database study of RA patients with at least one claim of RA and ≥ 2 claims of disease-modifying anti-rheumatic drug (DMARD); conventional synthetic (cs), biologic (b) or targeted synthetic (ts) DMARD with more than 6 months of follow-up from 01-Jan-2010 to 31-Dec-2020. Analyses were stratified for SUS-exclusive and SUS+ private user cohorts. We identified 250,251 patients with RA in DATASUS: mean age of 58.4 years, majority female (83%) and white (58%). 62% were SUS-exclusive and 38% SUS+ private. Most common bDMARDs were adalimumab and etanercept. Age (adjusted odds ratio 1.78 [50+]; 95% CI 1.57–2.01), SUS exclusive status (0.53; 0.47–0.59), distance to clinic [160+ km] (0.57; 0.45–0.72), and pre-index csDMARD claims (1.23; 1.08–1.41) were independent predictors of initiating a novel oral tsDMARD. Switching from bDMARD to tsDMARD, associations were similar, except for the direction of associations for SUS exclusive status (adjusted hazard ratio 1.10; 1.03–1.18), distance to clinic (1.18; 1.03–1.35), and number of previous bDMARD (0.15; 0.14–0.16). DATASUS is a source suitable for treatment-related analyses in RA reflecting the public health system in Brazil.

Case introduction: In this work we present a female infant patient with epilepsy of infancy with migrating focal seizures (EIMFS). Although many pharmacological schemes were attempted, she developed an encephalopathy with poor response to antiepileptic drugs and progressive cerebral dysfunction.Aim: To present the pharmacological response and therapeutic drug monitoring of a paediatric patient with a severe encephalopathy carrying a genetic variant in KCNT1 gene, whose identification led to include quinidine (QND) in the treatment regimen as an antiepileptic drug.Case report: Patient showed slow rhythmic activity (theta range) over left occipital areas with temporal propagation and oculo-clonic focal seizures and without tonic spasms three months after birth. At the age of 18 months showed severe impairments of motor and intellectual function with poor eye contact. When the patient was 4 years old, a genetic variant in the exon 24 of the KCNT1 gene was found. This led to the diagnosis of EIMFS. Due to antiepileptic treatment failed to control seizures, QND a KCNT1 blocker, was introduced as a therapeutic alternative besides topiramate (200 mg/day) and nitrazepam (2 mg/day). Therapeutic drug monitoring (TDM) of QND plasma levels needed to be implemented to establish individual therapeutic range and avoid toxicity. TDM for dose adjustment was performed to establish the individual therapeutic range of the patient. Seizures were under control with QND levels above 1.5 mcg/ml (65–70 mg/kg q. i.d). In addition, QND levels higher than 4.0 mcg/ml, were related to higher risk of suffering arrhythmia due to prolongation of QT segment. Despite initial intention to withdrawal topiramate completely, QND was no longer effective by itself and failed to maintain seizures control. Due to this necessary interaction between quinidine and topiramate, topiramate was stablished in a maintenance dose of 40 mg/day.Conclusion: The implementation of Precision Medicine by using tools such as Next Generation Sequencing and TDM led to diagnose and select a targeted therapy for the treatment of a KCNT1-related epilepsy in a patient presented with EIMFS in early infancy and poor response to antiepileptic drugs. QND an old antiarrhythmic drug, due to its activity as KCNT1 channel blocker, associated to topiramate resulted in seizures control. Due to high variability observed in QND levels, TDM and pharmacokinetic characterization allowed to optimize drug regimen to maintain QND concentration between the individual therapeutic range and diminish toxicity.

Abstract Background Children 90% of the 24 weeks of IPT (22 pick-ups) and the proportion of children who picked up the 24 weeks of IPT. The standard of care is a weekly pick-up with monthly check-ups in a health facility. Feasibility and acceptability of the intervention will be assessed through an interview with the caretaker. Discussion Unfavorable outcomes of TB in young children, high effectiveness of IPT, and low rates of IPT completion highlight the need to enhance adherence and completion of IPT among children

The DIII-D tokamak has elucidated crucial physics and developed projectable solutions for ITER and fusion power plants in the key areas of core performance, boundary heat and particle transport, and integrated scenario operation, with closing the core-edge integration knowledge gap being the overarching mission. New experimental validation of high-fidelity, multi-channel, non-linear gyrokinetic turbulent transport models for ITER provides strong confidence it will achieve Q ⩾ 10 operation. Experiments identify options for easing H-mode access in hydrogen, and give new insight into the isotopic dependence of transport and confinement. Analysis of 2,1 islands in unoptimized low-torque IBS demonstration discharges suggests their onset time occurs randomly in the constant β phase, most often triggered by non-linear 3-wave coupling, thus identifying an NTM seeding mechanism to avoid. Pure deuterium SPI for disruption mitigation is shown to provide favorable slow cooling, but poor core assimilation, suggesting paths for improved SPI on ITER. At the boundary, measured neutral density and ionization source fluxes are strongly poloidally asymmetric, implying a 2D treatment is needed to model pedestal fuelling. Detailed measurements of pedestal and SOL quantities and impurity charge state radiation in detached divertors has validated edge fluid modelling and new self-consistent ‘pedestal-to-divertor’ integrated modeling that can be used to optimize reactors. New feedback adaptive ELM control minimizes confinement reduction, and RMP ELM suppression with sustained high core performance was obtained for the first time with the outer strike point in a W-coated, compact and unpumped small-angle slot divertor. Advances have been made in integrated operational scenarios for ITER and power plants. Wide pedestal intrinsically ELM-free QH-modes are produced with more reactor-relevant conditions, Low torque IBS with W-equivalent radiators can exhibit predator-prey oscillations in T _e and radiation which need control. High- β _P scenarios with q _min > 2, q _95 –7.9, β _N > 4, β _T –3.3% and H _98y2 > 1.5 are sustained with high density ( $\bar n$ = 7E19 m ^−3 , f _G –1) for 6 τ _E , improving confidence in steady-state tokamak reactors. Diverted NT plasmas achieve high core performance with a non-ELMing edge, offering a possible highly attractive core-edge integration solution for reactors.

The objectives of NSTX-U research are to reinforce the advantages of STs while addressing the challenges. To extend confinement physics of low- A , high beta plasmas to lower collisionality levels, understanding of the transport mechanisms that set confinement performance and pedestal profiles is being advanced through gyrokinetic simulations, reduced model development, and comparison to NSTX experiment, as well as improved simulation of RF heating. To develop stable non-inductive scenarios needed for steady-state operation, various performance-limiting modes of instability were studied, including MHD, tearing modes, and energetic particle instabilities. Predictive tools were developed, covering disruptions, runaway electrons, equilibrium reconstruction, and control tools. To develop power and particle handling techniques to optimize plasma exhaust in high performance scenarios, innovative lithium-based solutions are being developed to handle the very high heat flux levels that the increased heating power and compact geometry of NSTX-U will produce, and will be seen in future STs. Predictive capabilities accounting for plasma phenomena, like edge harmonic oscillations, ELMs, and blobs, are being tested and improved. In these ways, NSTX-U researchers are advancing the physics understanding of ST plasmas to maximize the benefit that will be gained from further NSTX-U experiments and to increase confidence in projections to future devices.

A theoretical model is presented that for the first time matches experimental measurements of the pedestal width-height Diallo scaling in the low-aspect-ratio high- β tokamak NSTX. Combining linear gyrokinetics with self-consistent pedestal equilibrium variation, kinetic-ballooning, rather than ideal-ballooning plasma instability, is shown to limit achievable confinement in spherical tokamak pedestals. Simulations are used to find the novel Gyrokinetic Critical Pedestal constraint, which determines the steepest pressure profile a pedestal can sustain subject to gyrokinetic instability. Gyrokinetic width-height scaling expressions for NSTX pedestals with varying density and temperature profiles are obtained. These scalings for STs depart significantly from that of conventional aspect ratio tokamaks.

Meiofauna includes an astonishing diversity of organisms, whose census is far from being complete. Most classic ecological studies have focused on hard-bodied Ecdysozoan taxa (notably Copepoda and Nematoda), whose cuticle allows determination at species-level after fixation, rather than soft-bodied, Spiralian taxa, which most often lose any diagnostic feature in fixed samples. Yet, metabarcoding studies have recently revealed a species-richness of soft-bodied taxa comparable, and in cases superior, to that of Copepoda and Nematoda together. However, given objective difficulties inherent to their study, which necessarily has to be performed on living individuals, and their limited utilisation for ecological and applicative research, taxonomic expertise on soft-bodied organisms has declined over the years, and diversity of these phyla in most areas of the world is presently completely unknown. Here we present an expert-based survey of current knowledge on the composition and distribution of soft-bodied meiofaunal taxa in Italy, with special references to the predominantly or exclusively meiobenthic phyla Gastrotricha, Gnathostomulida, Platyhelminthes, Rotifera, Xenacoelomorpha, and macrofaunal taxa with conspicuous meiofaunal representatives (Annelida, Mollusca and Nemertea). A total of 638 described species have been reported from Italian coasts; furthermore, the existence of a large number of undescribed species is mentioned. Knowledge of Annelida, Gastrotricha, and Rotifera appears particularly detailed, placing Italy among the best-known country worldwide. In contrast, knowledge of Platyhelminthes and Xenacoelomorpha appears patchy, and limited to few areas. Sampling effort has been uneven, with most species recorded from the Tyrrhenian Sea, while large sections of the Adriatic and Ionian seas have been poorly explored. Results highlight the role that Marine Biological Stations, notably the Zoological Station “Anton Dohrn” in Naples, have had in promoting the study of soft-bodied taxa in Italy.

Ruditapes decussatus (Linnaeus, 1758) (Veneridae) is an Atlanto-Mediterranean bivalve whose populations have experienced reductions and, in some instances, hybridisation with allochthonous R. philippinarum. Acquisition of additional genetic knowledge concerning the present R. decussatus populations is essential to address adequate conservation plans for this species. For this purpose, we analysed a portion of the mtDNA cytochrome c oxidase subunit I (COI) region in populations from the western Mediterranean, where this species represents a harvested fishery resource. Our analyses revealed an overall lack of genetic structure within the western Mediterranean area, and the occurrence of mtDNA substructuring between the Aegean and Marmara seas and the remaining populations from the whole Mediterranean basin and the South European Atlantic coast. The results obtained for populations from Sardinia, where extensive restocking programmes have not been reported and where R. philippinarum is rare and localised, suggest that intensive harvesting and potential dispersal alone may have been able to shape the genetic variation identified in the local R. decussatus populations.

Measuring system of adverse weather phenomena. The adverse weather phenomena in nowadays are becoming an extraordinary problem in human life and human activity. Therefore, it seems very important to know the thresholds of adverse weather phenomena. These thresholds can be calculated in different ways, but some experience has shown that for weather elements which departures from normal follow the normal distribution suits to use the Gaussian curve of frequency distribution (temperature and pressure). For such weather elements the normal curve of frequency distribution may be used for classification of thresholds. For weather elements which departures do not depend on such a frequency distribution configuration (precipitation amounts) may be used a decile method. For wind speed thresholds, the Beaufort scale units can be used for calculation. In this paper the threshold scales for four basic weather elemnts are presented. All these scales contain four steps each. They are defined: normal, above normal, much above normal and extraordinary above normal or normal, below normal, much below normal and extraordinary below normal. The examples by observations of Meteorological Observatory in Belgrade are presented.

Convective clouds generate extreme rainfall events and flash floods in small areas with both large spatial and temporal variability. For this reason, the monitoring of the total accumulated precipitation fields at the surface with rain gauges and meteorological radars has both strengths and weakness. Alternatively, a numerical cloud model may be a useful tool to simulate convective precipitation for various analyses and predictions. The main objective of this paper is to show that the cloud-resolving model reproduces well the accumulated convective precipitation obtained from the rain gauge network data in the area with frequent split storms. We perform comparisons between observations and model samples of the areal accumulated convective precipitation for a 15-year period over treated area. Twenty-seven convective events have been selected. Statistical analyses reveal that the model areal accumulated convective precipitation closely match their observed values with a correlation coefficient of 0.80.

A new 1-D forced time-dependent model version with the hail size spectrum which includes only hail sized particles (larger than 0.5 cm in diameter; hereafter called realistic hail spectrum) was tested against its version which treats the hail size spectrum from zero to infinity (hereafter called idealized hail spectrum). Comparisons between simulated cloud top heights by two model versions and the observed values were also performed. Our experiments were done for 45 routine midday soundings. The intermodel comparisons show that the realistic hail spectrum changes systematically the values of hail, rain and cloud ice maxima mixing ratios as well as those for vertical velocity, as compared to the idealized hail spectrum. The values of the model cloud-top heights with the realistic hail spectrum mainly overestimate their idealized values for clouds higher than 9 km. The modeled values of maximum cloud top heights given by the realistic hail spectrum are better correlated with observed values (r = 0.90) than those with the idealized one (r = 0.83). The model version with the new formula simulates some characteristics of the microphysical fields which are in fair agreement with observations.

Gray-Box models (GBM) which combine a priori knowledge of a process – e.g. first principle equations - with a black-box modeling technique are useful when some parameters of the first-principle model – normally time-variant parameters like the specific kinetics of some bioprocesses- cannot be easily determined. In this case the black-box part of the GBM can be used to model the influence of input and state variables on the evolution of those parameters. The most commonly used black-box technique for GBM is Artificial Neural Networks (ANN). However Support Vector Machine (SVM) has shown its usefulness by improving over the performance of different supervised learning methods, either as classification models or as regression models. In this paper, a kind of SVM –the Least-Square Support Vector Machine (LS-SVM)- are used to develop a GBM for a solid-substrate fermentation (SSF) batch process, the growth of the filamentous fungus Gibberella fujikuroi. SSF are well known as low water consumption processes, therefore reducing liquid effluent treatment costs. They can also use agricultural wastes as substrates. Although these advantages lack of adequate models attempts to better exploit SSF processes at an industrial level. The aim of the present work is then to build a GBM to simultaneously estimate the specific growth kinetics and the specific production kinetics. Good results confirm that SVM can be effectively used for developing GBM for SSF processes.

Background. Acute Coronary Syndrome (ACS) is a clinical condition encompassing ST Segment Elevation Myocardial Infarction (STEMI), Non-ST Segment Elevation Myocardial Infarction (NSTEMI), and Unstable Angina (UA) and is characterized by ruptured coronary plaque, ischemic stress, and/or myocardial injury. Emergency department (ED) physicians are on the front lines of ACS management. The role of new antiplatelet agents ticagrelor and prasugrel in acute ED management of ACS has not yet been defined. Objective. To critically review clinical trials using ticagrelor and prasugrel in the treatment of ACS and inform practitioners of their potential utility in treating ACS in the ED. Results. Trials on the efficacy of ticagrelor and prasugrel achieve statistical significance in decreasing composite endpoints in select patient populations. Conclusion. The use of ticagrelor and prasugrel as first line ED treatment of ACS is not well established. Current evidence supports the use of several agents with the final decision based on treatment protocols conjointly developed between cardiology and emergency medicine (EM). Further clinical trials involving head-to-head trials or comparisons of drug-based strategies are required to show superiority in reducing cardiac endpoints with regard to ED initiation of treatment.

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A supercell convective storm is simulated by using a cloud-resolving model. Numerical experiments have been performed in 3D by using the same domain size, with a different spatial and temporal resolution of the model. High-resolution cloud model has been shown to represent convective processing quite well. Running the model in a high-resolution mode gives a more realistic view of the life cycle of convective storm, internal structure, and storm behavior. The storm structure and evolutionary properties are evaluated by comparing the modeled radar reflectivity to the observed radar reflectivity. The comparative analysis between physical parameters shows good agreement among both model runs and compares well with observations, especially using a fine spatial resolution. The lack of measurements of these species in the convective outflow region does not allow us to evaluate the model results with observations. A three-dimensional simulation using higher grid resolution mode exhibits interesting features which include a double vortex circulation, cell splitting, and secondary cell formation.

Polyethylene microplastics (PE-MPs), a whitish thermoplastic polymer with numerous applications, is one of the materials most widely used in the industrial sector, whereas tetrabromobisphenol A (TBBPA) is a brominated flame retardant. The aim of this study was to analyze the effects of PE-MPs and TBBPA on Rhinella arenarum tadpoles at the laboratory scale. Tadpoles were chronically exposed (30 days) to four treatments: PE-MPs (60 mg L−1), TBBPA (10 µg L−1), their mixture (PE-MPs + TBBPA), and dechlorinated water as negative control (CO). Biomarkers of enzymatic activity (acetylcholinesterase, AChE; carboxylesterase, CbE; glutathione reductase, GR; and glutathione-S-transferase, GST), hepatic physiological alteration (alkaline phosphatase; ALP activity, and cholesterol; CHOL level), and endocrine disruption through thyroid hormone (T4) levels were assessed. In addition, intestine and liver were histomorphologically evaluated. AChE activity in tadpoles was significantly inhibited after exposure to PE-MPs and TBBPA with respect to CO. In addition, CbE, GR, and ALP activities showed higher values in the mixture of PE-MPs+ TBBPA treatment than in CO, whereas CHOL level was higher in TBBPA and PE-MPs+ TBBPA treatments than in CO. GST activity did not show significant differences between treatments and CO. T4 levels increased significantly in all treatments with respect to CO. The intestinal structure of tadpoles exposed to PE-MPs and PE-MPs+ TBBPA showed signs of mechanical damage. The intestinal wall of tadpoles under PE-MPs, TBBPA and PE-MPs+ TBBPA treatments was thicker than that of CO individuals. The analysis of liver histology demonstrated the hepatotoxicity caused by PE-MPs+ TBBPA. This study provides quantitative evidence of the harmful effects of PE-MPs, TBBPA and their mixture on enzymatic and hormonal activities, and histological evidence of intestinal wall hypertrophy and liver damage of R. arenarum tadpoles.

Reproductive aspects of Dendropsophus sanborni (Anura, Hylidae) in northeastern Argentina. The aim of this investigation was to characterize reproductive aspects of Dendropsophus sanborni (Schmidt, 1944) (Anura, Hylidae) in the northwest of Corrientes province, in northeastern Argentina. The reproductive cycles of males and females, the existence of sexual dimorphism and the male’s vocalization period were analyzed. Samplings were made from September 2011 to August 2012. Dendropsophus sanborni showed a prolonged reproductive pattern because reproductive activity was observed during most part of the year. Calling males were recorded all months except in July. The spermatogenic cycle can be characterized as potentially continuous. In males, snout-vent length was significantly correlated with mean testicular volume. The species showed sexual dimorphism in body mass, with females larger than males. Post-ovulatory females were found from March to June and most females had oocytes at different stages of maturity, with abundant post-vitellogenic oocytes from August to December.

Hepatic cells are major sites of dengue virus (DENV) replication and liver injury constitutes a characteristic of severe forms of dengue. The role of hepatic cells in dengue pathogenesis is not well established, but since hepatocytes are the major source of plasma proteins, changes in protein secretion by these cells during infection might contribute to disease progression. Previously, we showed that DENV infection alters the secretion pattern of hepatic HepG2 cells, with α-enolase appearing as one of the major proteins secreted in higher levels by infected cells. ELISA analysis demonstrated that DENV infection modulates α-enolase secretion in HepG2 cells in a dose-dependent manner, but has no effect on its gene expression and on the intracellular content of the protein as assessed by PCR and western blot analyses, respectively. Two-dimensional western blots showed that both intracellular and secreted forms of α-enolase appear as five spots, revealing α-enolase isoforms with similar molecular weights but distinct isoeletric points. Remarkably, quantification of each spot content revealed that DENV infection shifts the isoform distribution pattern of secreted α-enolase towards the basic isoforms, whereas the intracellular protein remains unaltered, suggesting that post-translational modifications might be involved in α-enolase secretion by infected cells. These findings provide new insights into the mechanisms underlying α-enolase secretion by hepatic cells and its relationship with the role of liver in dengue pathogenesis. In addition, preliminary results obtained with plasma samples from DENV-infected patients suggest an association between plasma levels of α-enolase and disease severity. Since α-enolase binds plasminogen and modulates its activation, it is plausible to speculate the association of the increase in α-enolase secretion by infected hepatic cells with the haemostatic dysfunction observed in dengue patients including the promotion of fibrinolysis and vascular permeability alterations.

Objective: Recent studies have revealed a heterogeneous prevalence and presentation of PTSD across countries. It is crucial to assess the methodological and item-level measurement factors that contribute to variations in mental disorder rates across cultures. This study aimed to investigate the traumatic experiences of hospital workers by employing item analysis of the Impact of Event Scale-Revised (IES-R)., Methods: Data were collected from 1,000 employees of a large hospital during the COVID-19 pandemic and were further subjected to item response theory (IRT) analysis with respect to the discrimination (a) and difficulty (b) parameters of the item pool., Results: Our results demonstrated that the IES-R items had a good discriminative ability (a) and covered a range of distress severity (b) associated with traumatic experiences. The IES-R was found to be a reliable and informative instrument for assessing individuals with moderate to severe trauma-related distress across the spectrum of traumatic symptoms. In particular, items #10 ("jumpy or easily startled") and #6 (" thought about it when didn't mean to"), reflecting the PTSD domains of hyperarousal and intrusion, excelled in discriminating between different levels of traumatic distress. Conversely, items related to avoidance and sleep disturbance showed diminished discriminative ability., Conclusions: The item analysis of the IES-R may be used to assess trauma symptoms in the context of a traumatic exposure, thereby identifying the most discriminative and informative items of the PTSD measure in our context. Our findings may refine the IES-R and facilitate the development of a more effective scale with optimized item parameters., Competing Interests: The authors report no conflicts of interest.

Importance: Vascular injuries require urgent repair to minimize loss of limb and life. Standard revascularization relies on autologous vein or synthetic grafts, but alternative options are needed when adequate vein is not feasible and when clinical conditions preclude safe use of synthetic materials., Objective: To evaluate the performance of the acellular tissue engineered vessel (ATEV) in the repair of arterial injuries., Design, Setting, and Participants: Two open-label, single-arm, nonrandomized clinical trials, including 1 prospective civilian study (CLN-PRO-V005 [V005]) and 1 retrospective observational study in a war zone (CLN-PRO-V017 [V017]), were conducted from September 2018 to January 2024 (follow-up ongoing) at 19 level 1 trauma centers in the US and Israel and 5 frontline hospitals in Ukraine. Patients had vascular injury, no autologous vein available for emergent revascularization, and risk factors for wound infection. Data were analyzed from September 2023 to January 2024., Intervention: The ATEV is a bioengineered vascular conduit grown from human vascular cells, available off the shelf, and implantable without immunosuppression., Main Outcomes and Measures: Primary patency at day 30 was the primary outcome. Secondary outcomes included limb salvage, graft infection, and patient survival. A systematic literature review identified synthetic graft benchmarks in the treatment of arterial trauma for the same end points., Results: The V005 and V017 studies evaluated 69 and 17 patients, respectively, and included 51 in V005 and 16 in V017 with noniatrogenic arterial injuries of the extremities. The majority were male (V005, 38 [74.5%]; V017, 16 [100%]), the mean (SD) ages were similar (V005, 33.5 [13.6] years; V017, 34.2 [9.0] years), and the mean (SD) Injury Severity Scores were similar (V005, 20.8 [10.5]; V017, 20.1 [18.9]). Penetrating injuries dominated (V005, 29 patients [56.9%]; V017, 14 patients [87.5%]). At day 30 for the V005 and V017 trials, respectively, ATEV primary patency was 84.3% (95% CI, 72.0%-91.8%) and 93.8% (95% CI, 71.7%-98.9%); secondary patency was 90.2% (95% CI, 79.0%-95.7%) and 93.8% (95% CI, 71.7%-98.9%); amputation rate was 9.8% (95% CI, 4.3%-21.0%) and 0% (95% CI, 0.0%-19.4%); ATEV infection rate was 2.0% (95% CI, 0.4%-10.3%) and 0% (95% CI, 0.0%-19.4%); and death rate was 5.9% (95% CI, 2.0%-15.9%) and 0% (95% CI, 0.0%-19.4%) (no deaths attributed to the ATEV). Day 30 synthetic graft benchmarks were as follows: secondary patency, 78.9%; amputation, 24.3%; infection, 8.4%; and death, 3.4%., Conclusions and Relevance: Results of 2 single-arm trials in civilian and real-world military settings suggest that the ATEV provides benefits in terms of patency, limb salvage, and infection resistance. Comparing ATEV outcomes with synthetic graft benchmarks demonstrates improved outcomes in the treatment of acute vascular injuries of the extremities., Trial Registration: ClinicalTrials.gov Identifiers: NCT03005418, NCT05873959.

In addition to the usual slope and location parameters included in a regular two-parameter logistic model (2PL), the logistic positive exponent (LPE) model incorporates an item parameter that leads to asymmetric item characteristic curves, which have recently been shown to be useful in some contexts. Although this model has been used in some empirical studies, an identifiability analysis (i.e., checking the (un)identified status of a model and searching for identifiablity restrictions to make an unidentified model identified) has not yet been established. In this paper, we formalize the unidentified status of a large class of fixed-effects item response theory models that includes the LPE model and related versions of it. In addition, we conduct an identifiability analysis of a particular version of the LPE model that is based on the fixed-effects one-parameter logistic model (1PL), which we call the 1PL-LPE model. The main result indicates that the 1PL-LPE model is not identifiable. Ways to make the 1PL-LPE useful in practice and how different strategies for identifiability analyses may affect other versions of the model are also discussed., (© 2024 British Psychological Society.)

Introduction/objectives: Rheumatoid arthritis (RA) is a chronic autoimmune disease characterized by ongoing inflammation and degradation of synovial joints. The oral JAK inhibitor, upadacitinib, is approved for RA. We conducted an integrated safety analysis of upadacitinib 15 mg once daily (QD) in patients from Latin America (LATAM) versus the rest of the world (RoW)., Methods: Treatment-emergent adverse events (AEs) and laboratory data from six phase 3, randomized controlled trials, adjusted for upadacitinib 15 mg QD use in RA, were analyzed., Results: Overall, 3209 patients received upadacitinib 15 mg QD for 7024 patient-years (PY). LATAM patients (n = 725) had a mean upadacitinib exposure of 1518 PY. Baseline characteristics were generally similar between LATAM and RoW populations. AE rates (including serious/opportunistic infections, tuberculosis, and herpes zoster) and deaths were comparable between populations. LATAM patients had lower serious AE rates per 100 PY (9.4 vs 14.0 E/100 PY) and discontinuation-related AEs (3.9 vs 6.0 E/100 PY) versus RoW. Rates of cardiovascular events were low (≤ 0.5 E/100 PY) and similar between populations. Malignancies, excluding non-melanoma skin cancer, were less common in the LATAM population versus RoW (0.2 vs 1.0 E/100 PY). Laboratory abnormalities were similar between populations, with decreases in hemoglobin, lymphocyte, and neutrophil counts, and elevations in liver enzymes and creatine phosphokinase. Mean change from baseline in low- and high-density lipoprotein cholesterol was generally comparable between LATAM and RoW populations., Conclusion: Upadacitinib 15 mg QD demonstrated a consistent safety profile across LATAM and RoW patient populations, with no new safety risks observed., Trial Registration Numbers: SELECT-EARLY, NCT02706873; SELECT-NEXT, NCT02675426; SELECT-COMPARE, NCT02629159; SELECT-MONOTHERAPY, NCT02706951; SELECT-BEYOND, NCT02706847; SELECT-CHOICE, NCT03086343., (© 2023. The Author(s).)