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This is the PREFACE to the Special Issue "Queueing-inventory: analytical and simulation modeling and classical and retrial queues and inventory". The year 2022 was the 30th anniversary of Queueing-inventory. It was in that connection that the guest editors requested Professor Endre Boros, the Editor-in-Chief of Annals of Operations Research, for permission to guest edit a special issue. This was granted by the Editorial Board of the journal. [ABSTRACT FROM AUTHOR]

Endoscopic ultrasound (EUS)-guided vascular interventions were first reported in 2000 in a study that evaluated the utility of EUS in sclerotherapy of esophageal varices. Currently, gastric variceal therapy and portosystemic pressure gradient (PPG) measurements are the most widely utilized applications. Ectopic variceal obliteration, splenic artery embolization, aneurysm/pseudoaneurysm treatment, portal venous sampling, and portosystemic shunt creation using EUS are some of the other emerging interventions. Since the release of the American Gastroenterological Association (AGA)'s commentary in 2023, which primarily endorses EUS-guided gastric variceal therapy and EUS-PPG measurement, several new studies have been published supporting the use of EUS for various vascular conditions. In this review, we present the recent advances in this field, critically appraising new studies and trials. [ABSTRACT FROM AUTHOR]

This article deals with a repairable k-out-of-n: G system with retrial feature and two maintenance policies. All components in the system have two failure modes, mode a failure and mode b failure. When a component fails, the failed component will be repaired instantly if the repair equipment is idle. Otherwise, it enters into a retrial orbit and tries again after some time until it is repaired. The single repair equipment may be subject to breakdown in a busy period, and in order to improve system reliability, the idle repair equipment will be performed preventive maintenance. The Markov process theory and Laplace transform method are adopted to compute the reliability indexes of the system. Also, four optimization design models are constructed to determine the optimal repair rates of the components with two failure modes, and the minimization problems of the total expected cost function per unit time and the cost-effectiveness ratio are solved. To verify the correctness of the model, numerical analysis is executed to demonstrate the impact of each parameter on system reliability indexes, the optimal solutions of different optimization design models are obtained by using differential evolution algorithm and genetic algorithm. [ABSTRACT FROM AUTHOR]

This paper analyzes the M/M/c queueing system with server working breakdown and impatient customers under the classical truncated retry strategy. The steady-state equilibrium conditions of the system are obtained using the matrixgeometric solution method. Then the steady-state probabilities and the performance indicators of the system in the steadystate case are obtained using the Markov process theory and Gauss-Seidel iterative algorithm. Numerical experiments are conducted to assess the system’s steady-state performance indicators. Finally, we developed an optimization model for the system and derived the optimal parameters from the analysis of the optimization function. [ABSTRACT FROM AUTHOR]

The cloud storage service, known for its flexible and expandable nature, often has difficulties managing operating costs while ensuring dependable service and quick response times. This investigation presents a novel approach to optimizing cost efficiency in cloud storage systems by applying particle swarm optimization of the Markovian retrial queueing model in a generic setup by incorporating the working vacation and users' discouragement behavior. Some users may opt not to enter the system or join the retry pool to wait for their turn if the server is occupied. After returning from working vacation, if there is one user available for service, the server can interrupt the vacation period. The server is subject to breakdown and can be recovered after getting the repair. In the proposed model, the server is prone to catastrophes and can fail at any time, leading to the entire system breaking down, and no users being able to access it during this period. Chapman–Kolmogorov (CK) steady-state equations associated with the quasi-birth-death (QBD) process are constructed to make a mathematical design. The governing equations framed to derive the queue length distributions and various performance indices are solved using the recursive method and difference equation theory. The fuzzified parameters are used to develop the FM/FM/1/WV model, which is analyzed using a parametric nonlinear programming approach. To determine the optimal design parameters, the cost minimization problem has been done using the quasi-Newton method and particle swarm optimization. This model incorporates features such as server failures, retrials, and catastrophes, thereby reflecting the complex nature of cloud storage operations. A suitable illustration of cloud storage is taken for both classical and fuzzified models to facilitate the numerical results of performance indices and optimal decision descriptors. [ABSTRACT FROM AUTHOR]

The operation of many queueing systems is adequately described by the structured multidimensional continuous-time Markov chains. The most well-studied classes of such chains are level-independent Quasi-Birth-and-Death processes, G I / M / 1 type and M / G / 1 type Markov chains, generators of which have the block tri-diagonal, lower- and upper-Hessenberg structure, respectively. All these classes assume that the matrices of transition rates are quasi-Toeplitz. This property greatly simplifies their analysis but makes them inappropriate for the study of many important systems, e.g., retrial queues with a retrial rate depending on the number of customers in orbit, queues with impatient customers, etc. The importance of such systems attracts significant interest to their analysis. However, in the literature, there is a methodological gap relating to the ergodicity condition of the corresponding Markov chains. To fulfill this gap and facilitate the analysis of a wide range of such systems, we show that under non-restrictive assumptions, the following hold true: (i) if the customers can balk or are impatient or non-persistent, then the Markov chain describing the behavior of the system belongs to the class of asymptotically quasi-Toeplitz Markov chains; (ii) this chain is ergodic; (iii) known algorithms can be applied for the calculation of the stationary distribution of the corresponding queueing system. [ABSTRACT FROM AUTHOR]

Background: Malaria transmission is known to be perennial and heterogeneous in Benin. Studies assessing local malaria prevalence, transmission levels and vector characteristics are critical for designing, monitoring and evaluating new vector control interventions in community trials. We conducted a study in the Zakpota sub-district of central Benin to collect baseline data on household characteristics, malaria prevalence, vector characteristics and transmission dynamics in preparation for a randomised controlled trial to evaluate the community impact of VECTRON™ T500, a new broflanilide indoor residual spraying (IRS) product. Methods: A total of 480 children under 5 years of age from the 15 villages of the sub-district were tested for malaria by rapid diagnostic tests (RDTs). Mosquitoes were collected by human landing catches (HLCs), pyrethrum spray catches (PSCs) and Centers for Disease Control and Prevention miniature light traps (CDC-LTs) in selected houses in each village to assess vector density, composition, vector infectivity and prevalence of insecticide resistance markers. Bioassays were performed to detect vector susceptibility to pyrethroids, broflanilide (6 µg/bottle) and clothianidin (90 µg/bottle). Results: A total of 9080 households were enumerated in the 15 study villages. Insecticide-treated net (ITN) usage was > 90%, with 1–2 ITNs owned per household. Houses were constructed mainly with cement (44%) and mud (38%) substrates or a mixture of cement and mud (18%), and 60% of them had open eaves. The overall prevalence of P. falciparum infection was 19% among surveyed children: 20% among females and 18% among males. The haemoglobin rate showed an anaemia (< 11 g/dl) prevalence of 66%. Anopheles coluzzii and An. gambiae sensu stricto (s.s.) were the two vector species present at an overall proportion of 46% versus 54%, respectively. The human biting rate was 2.3 bites per person per night (b/p/n) and biting occurred mostly indoors compared with outdoors (IRR = 0.776; P = 0.001). The overall proportion of outdoor biting was 44% and exceeded indoor biting in three villages. The sporozoite rate was 2% with a combined yearly entomological inoculation rate (EIR) of 16.1 infected bites per person per year (ib/p/y). There was great variability in malaria transmission risk across the villages, with EIR ranging from 0 to 29.3 ib/p/y. The vector population showed a high intensity of resistance to pyrethroids across the study villages but was largely susceptible to broflanilide and clothianidin. Conclusions: This study found high levels of malaria prevalence, vector density and transmission in the Zakpota sub-district despite the wide use of insecticide-treated nets. The vector population was mostly indoor resting and showed a high intensity of pyrethroid resistance but was generally fully susceptible to broflanilide. These findings demonstrated the suitability of the study area for the assessment of VECTRON™ T500 in a community randomised trial. [ABSTRACT FROM AUTHOR]

In light of the changing climate that jeopardizes future food security, genomic selection is emerging as a valuable tool for breeders to enhance genetic gains and introduce high‐yielding varieties. However, predicting grain yield is challenging due to the genetic and physiological complexities involved and the effect of genetic‐by‐environment interactions on prediction accuracy. We utilized a chained model approach to address these challenges, breaking down the complex prediction task into simpler steps. A diversity panel with a narrow phenological range was phenotyped across three Mediterranean environments for various morpho‐physiological and yield‐related traits. The results indicated that a multi‐environment model outperformed a single‐environment model in prediction accuracy for most traits. However, prediction accuracy for grain yield was not improved. Thus, in an attempt to ameliorate the grain yield prediction accuracy, we integrated a spectral estimation of spike number, being a major wheat yield component, with genomic data. A machine learning approach was used for spike number estimation from canopy hyperspectral reflectance captured by an unmanned aerial vehicle. The spectral‐based estimated spike number was utilized as a secondary trait in a multi‐trait genomic selection, significantly improving grain yield prediction accuracy. Moreover, the ability to predict the spike number based on data from previous seasons implies that it could be applied to new trials at various scales, even in small plot sizes. Overall, we demonstrate here that incorporating a novel spectral‐genomic chain‐model workflow, which utilizes spectral‐based phenotypes as a secondary trait, improves the predictive accuracy of wheat grain yield. [ABSTRACT FROM AUTHOR]

Objective: In this review, the authors update the 2018 position statement of the American Psychiatric Association Council of Research Workgroup on Biomarkers and Novel Treatments on pharmacogenomic (PGx) tools for treatment selection in depression. Methods: The literature was reviewed for new clinical trials and meta-analyses, published from 2017 to 2022, of studies using PGx tools for treatment selection in depression. The blinding and control conditions, as well as primary and secondary outcomes and post hoc analyses, were summarized. Results: Eleven new clinical trials and five meta-analyses were identified; all studies had primary outcome measures related to speed or efficacy of treatment response. Three trials (27%) demonstrated efficacy on the primary outcome measure with statistical significance; the three studies used different PGx tools; one study was open-label and the other two were small single-blind trials. Five trials (45%) did not detect efficacy with statistical significance on either primary or secondary outcome measures. Only one trial (9%) used adverse events as a primary outcome measure. All studies had significant limitations; for example, none adopted a fully blinded study design, only two studies attempted to blind the treating clinician, and none incorporated measures to estimate the effectiveness of the blinds or the influence of lack of blinding on the study results. Conclusions: The addition of these new data do not alter the recommendations of the 2018 report, or the advice of the U.S. Food and Drug Administration, that the evidence does not support the use of currently available combinatorial PGx tools for treatment selection in major depressive disorder. Priority efforts for future studies and the development and testing of effective tools include fully blinded study designs, inclusion of promising genetic variants not currently included in any commercially available tests, and investigation of other uses of pharmacogenomics, such as estimating the likelihood of rare adverse drug effects, rather than increasing the speed or magnitude of drug response. [ABSTRACT FROM AUTHOR]

Background: Over the years, Indian regulations have undergone numerous amendments, including stringent reporting deadlines, relatedness requirements, and compensation obligations for serious adverse event (SAE). A historic change, new drugs and trial rules-2019, was proposed on March 19, 2019. The purpose of the study was to ascertain whether various stakeholders were reporting in accordance with the evolving SAE criteria. Materials and Methods: Data were retrieved after the Ethics Committee’s approval between August 2014 and December 2021. Data gathered before March 19, 2019, were categorized as “BEFORE” data, while the remaining data were categorized as “AFTER.” Utilizing causality, on-site SAE reporting, and the ethics committee review procedure, we evaluated the compliance. The data were evaluated using descriptive statistics, and the Chi-square or Mann–Whitney tests were used to compare the “BEFORE” and “AFTER” groups. Results: A total of 77 SAEs were reported in 26 clinical trials, where most clinical trials were phase III. Endocrine projects made up 9/26 (34.61%). In the cardiology studies, the greatest SAE distribution was 21 SAEs/89 participants(23.59%) with approximately 48% of these being vascular. The “AFTER” group noticed a decrease in the total number and length of SAE subcommittee meetings. In the “AFTER” group, there was a significantly higher median number of agenda items/meetings (8 [4.5–10.75]) (P < 0.0001). The median interval between the onset of SAE and the first reporting date, however, was just 1 day (interquartile range: 1–5 days). In nondeath SAEs, there was no significant difference in the compensation paid. In the “AFTER” group, there were no discrepancies in reporting SAE. Conclusion: There is acceptable adherence to SAE reporting criteria. [ABSTRACT FROM AUTHOR]

As an effective means to improve system reliability, cold standby redundancy design has been applied in many fields. Studies on the reliability of systems with retrial mechanisms mainly focus on the assumption of continuous time, but for some engineering systems whose states cannot be continuously monitored, it is of great theoretical and practical value to establish and analyze the reliability model of the discrete-time cold standby repairable retrial system. In this paper, the lifetime, repair time, and retrial time of each component were described by geometric distribution, and the reliability and optimal design models of a discrete-time cold standby retrial system were developed. Two different models were proposed based on two types of priority rules. According to the discrete-time Markov process theory, the transition probability matrix of the system states was given. The availability, reliability function, mean time to first failure (MTTFF) of the system, and other performance measures were obtained using the iterative algorithm of the difference equation, and the generative function method, algorithms for calculating stationary probability, and transient probability of the system were designed. The particle swarm optimization (PSO) algorithm was used to determine the optimal values of the repair rate and retrial rate corresponding to the minimum value of the cost-benefit ratio. Moreover, numerical analysis was performed to show the influence of each parameter on the system reliability and the cost-benefit ratio. The reliability measures of the systems with and without retrial mechanism were analytically compared. [ABSTRACT FROM AUTHOR]

Non-Tuberculous mycobacteria (NTM) are opportunistic environmental bacteria. Globally, NTM incidence is increasing and modeling suggests that, without new interventions, numbers will continue to rise. Effective treatments for NTM infections remain suboptimal. Standard therapy for Mycobacterium avium complex, the most commonly isolated NTM, requires a 3-drug regime taken for approximately 18 months, with rates of culture conversion reported between 45 and 70%, and high rates of relapse or reinfection at up to 60%. New therapeutic options for NTM treatment are urgently required. A survey of ongoing clinical trials for new NTM therapy listed on ClinicalTrials.Gov using the terms 'Mycobacterium avium', 'Mycobacterium abscessus', 'Mycobacterium intracellulare', 'Non tuberculous Mycobacteria' and 'Nontuberculous Mycobacteria' and a selection criterion of interventional studies using antibiotics demonstrates that most trials involve dose and combination therapy of the guideline based therapy or including one or more of; Amikacin, Clofazimine, Azithromycin and the anti-TB drugs Bedaquiline and Linezolid. The propensity of NTMs to form biofilms, their unique cell wall and expression of both acquired and intrinsic resistance, are all hampering the development of new anti-NTM therapy. Increased investment in developing targeted treatments, specifically for NTM infections is urgently required. [ABSTRACT FROM AUTHOR]

Introduction: Models of attachment and information processing suggest that the attention infants allocate to social information might occur in a schemadriven processing manner according to their attachment pattern. A major source of social information for infants consists of facial expressions of emotion. We tested for differences in attention to facial expressions and emotional discrimination between infants classified as securely attached (B), insecureavoidant (A), and insecure-resistant (C). Methods: Sixty-one 14-month-old infants participated in the Strange Situation Procedure and an experimental task of Visual Habituation and Visual Paired-Comparison Task (VPC). In the Habituation phase, a Low-Arousal Happy face (habituation face) was presented followed by a VPC task of 6 trials composed of two contrasting emotional faces always involving the same actress: the one used in habituation (trial old face) and a new one (trial new face) portraying changes in valence (Low-Arousal Angry face), arousal (High-Arousal Happy face), or valence + arousal (High-Arousal Angry face). Measures of fixation time (FT) and number of fixations (FC) were obtained for the habituation face, the trial old face, the trial new face, and the difference between the trial old face and the trial new face using an eye-tracking system. Results: We found a higher FT and FC for the trial new face when compared with the trial old face, regardless of the emotional condition (valence, arousal, valence + arousal contrasts), suggesting that 14-month-old infants were able to discriminate different emotional faces. However, this effect differed according to attachment pattern: resistant-attached infants (C) had significantly higher FT and FC for the new face than patterns B and A, indicating they may remain hypervigilant toward emotional change. On the contrary, avoidant infants (A) revealed significantly longer looking times to the trial old face, suggesting overall avoidance of novel expressions and thus less sensitivity to emotional change. Discussion: Overall, these findings corroborate that attachment is associated with infants' social information processing. [ABSTRACT FROM AUTHOR]

Purpose: Low frequency EPR can noninvasively detect endogenous free radical melanin in melanocytic skin lesions and could potentially discriminate between benign atypical nevi and malignant melanoma lesions. We recently succeeded in demonstrating the ability of clinical EPR to noninvasively detect the endogenous melanin free radical in skin lesions of patients. However, the signal-to-noise ratio (SNR) was extremely low warranting further research to boost the sensitivity of detection. In the present study, we assessed the performance of a clinical EPR system with the capability to perform multi-harmonic (MH) analysis for the detection of melanin. Procedures: The sensitivity of MH-EPR was compared with a classical continuous wave (CW)-EPR (1st harmonic) detection in vitro in melanin phantoms, in vivo in melanoma models with cells implanted in the skin, in lymph nodes and having colonized the lungs, and finally on phantoms placed at the surface of human skin. Results: In vitro, we observed an increase in SNR by a factor of 10 in flat melanin phantoms when using MH analysis compared to CW combined with an increase in modulation amplitude. In B16 melanomas having grown in the skin of hairless mice, we observed a boost in sensitivity in vivo similar to that observed in vitro with the capability to detect melanoma cells at an earlier stage of development. MH-EPR was also able to detect non-invasively the melanin signal coming from melanoma cells present in lymph nodes as well as in lungs. We also observed a boost of sensitivity using phantoms of melanin placed at the surface of human skin. Conclusions: Overall, our results are paving the way for new clinical trials that will use MH clinical EPR for the characterization of pigmented skin lesions. [ABSTRACT FROM AUTHOR]

Post-acquittal retrials for substantially the same offence are possible in jurisdictions that have provided statutory modifications to the common law double jeopardy principle. The pleas in bar of prosecution, autrefois acquit (previously acquitted) and autrefois convict (previously convicted), are predicated on a final verdict of acquittal or conviction by a court of competent criminal jurisdiction for substantially the same offence. Differentiating similarities between the increasing volume of overlapping offences is the most litigated aspect of the double jeopardy principle. Seminal common law jurisdictions have adopted variations of the same elements approach that examines whether two or more offences arising out of the same prohibited conduct are the same based on an assessment of whether there is an element in one offence not in the comparable offence. Through doctrinal analysis of superior court jurisprudence in the Unites States, England and Wales, Canada, Australia and New Zealand, this article evaluates judicial formulations for determining the sameness of offences in comparative perspective. While the analysis is intrinsic to each jurisdiction, judicial formulations may nonetheless shed light on similar issues coming before courts of criminal justice in cognate jurisdictions. [ABSTRACT FROM AUTHOR]

An M/M/1 retrial queue with working vacation and interruption in Bernoulli schedule under Ncontrol pattern is investigated in this article. To describe the system, we employ a QBD analogy. The model’s stability condition is deduced. The stationary probability distribution is generated by utilizing the matrix-analytic technique. The performance measures and special cases are designed. The model’s firmness is demonstrated numerically. [ABSTRACT FROM AUTHOR]

In this study, the dissipation problem of nonlinear pulse in mono mode optical fibers which is governed by the Fokas system (FS) is considered. The solutions of this system have an important role in comprehending the different wave structures in physical settings. Therefore, a new version of the trial equation method (NVTEM) is employed to present the new exact wave solutions of the FS. The advantage of the NVTEM is to use different root possibilities of a polynomial which shape the solutions of the related model. Primarily this system is converted to a nonlinear ordinary differential equation (NODE) via the traveling wave transform to apply the proposed method. Various exact wave solutions to the FS are obtained such as rational function, exponential function, hyperbolic function, and Jacobi elliptic function solutions. Thus, we have revealed solutions featly which are unlike the wave solutions previously found by other analytical methods. The present results depict the formation and development of such waves and their interactions. The exhibition of the solutions is given by 3D plots together with the corresponding 2D plots. The outcomes have shown that the proposed technique is abundant in achieving different wave solutions of many nonlinear differential equations in the field of optics. [ABSTRACT FROM AUTHOR]

The paper deals with Markovian multiserver retrial queuing system with exponential abandonments, two types of arrivals: Fresh calls and Handover calls and waiting places in the service area. This model can be used for analysing a cellular mobile network, where the service area is divided into cells. In this paper, the number of customers in the system and in the orbit form a level-dependent quasi-birth-and-death process, whose stationary distribution is expressed in terms of a sequence of rate matrices. First, we derive the Taylor series expansion for nonzero elements of the rate matrices. Then, by the expansion results, we obtain an asymptotic upper bound for the stationary distribution of both the number of busy channels and the number of customers in the orbit. Furthermore, we present some numerical results to examine the performance of the system. [ABSTRACT FROM AUTHOR]

In this article, we consider a make-to-stock queueing system with retrial customers. Upon their arrival, customers make a decision to either join the system or not based on a reward–cost function. If customers join the retrial queue, they become repeat customers. Each repeat customer repeats their demand after an exponential amount of time until they have been successfully served. We explore the equilibrium strategies of customers in both the almost observable and unobservable cases. Furthermore, we also analyze the expected costs of the entire system based on the customers' behavior in these two cases. Additionally, we determine the optimal inventory levels in both cases through numerical experiments. [ABSTRACT FROM AUTHOR]

This mini-review summarizes the clinical outcomes and antifungal susceptibility results, where available, for three new antifungals, including fosmanogepix, ibrexafungerp, and rezafungin, against Candida isolates cultured from patients in clinical trials. When reported, most of the data were generated by the Clinical and Laboratory Standards Institute (CLSI) broth microdilution method or by both the CLSI and European Committee on Antimicrobial Susceptibility Testing (EUCAST) methodologies. For fosmanogepix, we summarize the in vitro data for C. auris isolates from 9 patients and for Candida spp. cultured from 20 patients in two clinical trials. Ibrexafungerp has also been evaluated in several clinical trials. From conference proceedings, a total of 176 Candida isolates were evaluated in the FURI and CARES studies, including 18 C. auris isolates (CARES study). However, MIC data are not available for all clinical isolates. Results from the ReSTORE rezafungin phase 3 clinical study also included in vitro results against Candida spp., but no patients with C. auris infections were included. In conclusion, this mini-review summarizes insights regarding clinical outcomes and the in vitro activity of three new antifungals against Candida spp. cultured from patients in clinical trials. [ABSTRACT FROM AUTHOR]

Following a request from the European Commission, the Panel on Additives and Products or Substances used in Animal Feed (FEEDAP) was asked to deliver a scientific opinion on the efficacy of ROVABIO® ADVANCE (liquid and solid) which contains endo‐1,4‐beta‐xylanase and endo‐1,3(4)‐beta‐glucanase produced with Talaromyces versatilis IMI 378536 and DSM 26702 as a zootechnical feed additive for weaned piglets at the recommended use level of 1800 U xylanase and 1250 U glucanase per kg feed. In a previous assessment, three long‐term trials in weaned piglets were submitted. Two of them were considered to support the efficacy of the additive while a third trial was not further considered due to the large number of veterinary treatments applied. A new trial was provided to support the efficacy of the additive, but it did not show a significant improvement of the performance parameters at the minimum recommended use level. Due to the lack of sufficient data, the FEEDAP Panel is not in the position to conclude on the efficacy of the additive for the target species. [ABSTRACT FROM AUTHOR]

We examined a retrial make-to-stock system based on a double-ended queue. When the queue length was negative, the inventory system contained only products, and customers were waiting in the retrial queue when the queue length was positive. We developed a model to study the expected cost of the entire system with strategic customers in the observable case and the fully observable case. We also obtained the optimal inventory levels under these two levels of information based on numerical experiments. [ABSTRACT FROM AUTHOR]

Background: Immune checkpoint inhibitor (ICI)-based therapy such as atezolizumab plus bevacizumab or durvalumab plus tremelimumab became mainstream first-line systemic treatment in advanced hepatocellular carcinoma (HCC) patients since remarkably superior efficacy of ICI-based therapy compared to tyrosine kinase inhibitors (TKIs) was reported in two recent randomized controlled trials (RCTs) (IMbrave150, HIMALAYA). However, the optimal second-line therapy after treatment failure of first-line ICI-based therapy remains unknown as no RCT has examined this issue. Summary: Therefore, at present, most clinicians are empirically treating patients with TKIs or retrial of ICI or locoregional treatment (LRT) modality such as transarterial therapy, radiofrequency ablation, and radiation therapy in this clinical setting without solid evidence. In this review, we will discuss current optimal strategies for second-line treatment after the failure of first-line ICI-based therapy by reviewing published studies and ongoing prospective trials. Key Messages: Clinicians should consider carefully whether to treat the patients with TKI, other ICI-based therapy, or LRT in this situation by considering several factors including liver function reserve, performance status, adverse events of previous therapy, and presence of lesion that can consider LRT such as oligoprogression and vascular invasion. In the meantime, we await the results of ongoing prospective trials to elucidate the best management options. [ABSTRACT FROM AUTHOR]

Object detection has become a popular tool of deep learning in the era of digital manufacturing. In this study, the most powerful and efficient object detection algorithm, i.e., You Only Look Once (YOLO) algorithm, was used to detect anomalies in deposited beads of wire-arc additive manufacturing (WAAM) using melt pool images. This study used the latest version of YOLO algorithm to train and validate the custom image dataset of the melt pool obtained by conducting experiments using a robotic-controlled WAAM. The mean average precision (mAP) for the "Regular bead" class and the "Irregular bead" class reached 99% at an Intersection over Union (IoU) threshold of 0.5, for both training and validation. When the model was tested for new or unseen datasets by conducting four new experimental trials, the mAP value for the "Regular bead" class reached 98.47% and for the "Irregular bead" class reached 96.68% at an average processing time of 0.014 s/frame. The object detection algorithm YOLO has shown an excellent processing time of 15 ms per frame, which shows its potential for real-time application in the manufacturing industry. [ABSTRACT FROM AUTHOR]

Background: The discovery of the epidermal growth factor receptor (EGFR) mutation, especially in adenocarcinoma, has led to a major change in the treatment of non-small-cell lung cancer (NSCLC). This study investigated the relationship between the EGFR mutation status and the carcinoembryonic antigen (CEA) levels at the time of diagnosis. Materials and Methods: A total of 102 patients with EGFR mutation and tested CEA levels were recruited for this study. Of the patients, 24 were EGFR mutants (23.5%), while 78 patients (76.5%) did not harbor any EGFR mutations. Results: The CEA levels did not differ across groups. Additionally, the CEA levels were analyzed between female and male patients separately due to EGFR mutations; no difference was observed. When the CEA levels were categorized as positive or negative based on different cut-off values, such as 5 and 10 ng/ml, no statistical difference was found between groups. Conclusion: In this study, no relationship between EGFR mutation and pre-treatment CEA levels was observed. Despite positive trials having shown a predictive value of CEA levels for EGFR mutation, more clinical trials are needed to elucidate the racial, clinical, and pathological differences of the study populations. Most studies have been located in the Far East, but new trials in Caucasian, African, and Hispanic populations are still lacking. [ABSTRACT FROM AUTHOR]

This work focuses over the performability analysis of a multi-server retrial queueing model with phase-type inter-retrial times in cellular networks. It is considered that the pattern of the new call arrival and handoff call arrival follows marked Markovian arrival process. The service times of both types of calls are phase-type (PH) distributed with different parameters, and inter-failure & inter-repair times of channels are exponentially distributed. For the prioritization of handoff calls, G channels are kept in reserve for handoff calls. When all the available channels, say S , are busy at the arrival epoch of a handoff call, the handoff call will be dropped. Whereas a new call will be blocked and will have an option to join the orbit of infinite capacity or leave the system without getting the connection, if at least S − G channels are busy. A new call in the orbit, termed as retrial call, retries to get the connection after a random interval which follows PH distribution. This model is analyzed as a level-dependent-quasi-birth-death process by applying an efficient method. Through numerical illustrations, the behavior of performance measures depending on the various relevant intensities is discussed. [ABSTRACT FROM AUTHOR]

This paper studies an M/M/1 retrial queue with negative customers, passive breakdown, and delayed repairs. Assume that the breakdown behavior of the server during idle periods is different from that during busy periods. Passive breakdowns may occur when the server is idle, due to the lack of monitoring of the server during idle periods. When the passive breakdown occurs, the server does not get repaired immediately and enters a delayed repair phase. Negative customers arrive during the busy period, which will cause the server to break down and remove the serving customers. Under steady-state conditions, we obtain explicit expressions of the probability generating functions for the steady-state distribution, together with some important performance measures for the system. In addition, we present some numerical examples to illustrate the effects of some system parameters on important performance measures and the cost function. Finally, based on the reward-cost structure, we discuss Nash equilibrium and socially optimal strategy and numerically analyze the influence of system parameters on optimal strategies and optimal social benefits. [ABSTRACT FROM AUTHOR]

A multi-server retrial queuing model is under study. Arrivals occur according to the Markov arrival process (MAP). Aiming to increase the probability of immediate access of arriving requests to service, control by the admission of retrying requests, which did not succeed to start service immediately after arrival, is supposed. A control strategy is determined by the set of the integer thresholds defined for each value of the underlying Markov chain of the MAP. Any retrying request is accepted for service if the number of busy servers is less than the threshold corresponding to the current state of the underlying Markov chain. Retrying requests are impatient and can depart from the system without receiving service. Dynamics of the system is described by the three-dimensional Markov chain. Its generator is obtained, steady-state probabilities are computed and formulas for computation of certain performance measures are given. Numerical examples are presented including illustration of a possibility to use the obtained results for managerial goals. [ABSTRACT FROM AUTHOR]

Introduction: Models of attachment and information processing suggest that the attention infants allocate to social information might occur in a schemadriven processing manner according to their attachment pattern. A major source of social information for infants consists of facial expressions of emotion. We tested for differences in attention to facial expressions and emotional discrimination between infants classified as securely attached (B), insecureavoidant (A), and insecure-resistant (C). Methods: Sixty-one 14-month-old infants participated in the Strange Situation Procedure and an experimental task of Visual Habituation and Visual Paired- Comparison Task (VPC). In the Habituation phase, a Low-Arousal Happy face (habituation face) was presented followed by a VPC task of 6 trials composed of two contrasting emotional faces always involving the same actress: the one used in habituation (trial old face) and a new one (trial new face) portraying changes in valence (Low-Arousal Angry face), arousal (High-Arousal Happy face), or valence + arousal (High-Arousal Angry face). Measures of fixation time (FT) and number of fixations (FC) were obtained for the habituation face, the trial old face, the trial new face, and the difference between the trial old face and the trial new face using an eye-tracking system. Results: We found a higher FT and FC for the trial new face when compared with the trial old face, regardless of the emotional condition (valence, arousal, valence + arousal contrasts), suggesting that 14-month-old infants were able to discriminate different emotional faces. However, this effect differed according to attachment pattern: resistant-attached infants (C) had significantly higher FT and FC for the new face than patterns B and A, indicating they may remain hypervigilant toward emotional change. On the contrary, avoidant infants (A) revealed significantly longer looking times to the trial old face, suggesting overall avoidance of novel expressions and thus less sensitivity to emotional change. Discussion: Overall, these findings corroborate that attachment is associated with infants' social information processing. [ABSTRACT FROM AUTHOR]

Cold static storage preservation of donor hearts for periods longer than 4 hours increases the risk of primary graft dysfunction (PGD). The aim of the study was to determine if hypothermic oxygenated perfusion (HOPE) could safely prolong the preservation time of donor hearts. We conducted a nonrandomized, single arm, multicenter investigation of the effect of HOPE using the XVIVO Heart Preservation System on donor hearts with a projected preservation time of 6 to 8 hours on 30-day recipient survival and allograft function post-transplant. Each center completed 1 or 2 short preservation time followed by long preservation time cases. PGD was classified as occurring in the first 24 hours after transplantation or secondary graft dysfunction (SGD) occurring at any time with a clearly defined cause. Trial survival was compared with a comparator group based on data from the International Society of Heart and Lung Transplantation (ISHLT) Registry. We performed heart transplants using 7 short and 29 long preservation time donor hearts placed on the HOPE system. The mean preservation time for the long preservation time cases was 414 minutes, the longest being 8 hours and 47 minutes. There was 100% survival at 30 days. One long preservation time recipient developed PGD, and 1 developed SGD. One short preservation time patient developed SGD. Thirty day survival was superior to the ISHLT comparator group despite substantially longer preservation times in the trial patients. HOPE provides effective preservation out to preservation times of nearly 9 hours allowing retrieval from remote geographic locations. [ABSTRACT FROM AUTHOR]

Non‐inferiority trials compare new experimental therapies to standard ones (active control). In these experiments, historical information on the control treatment is often available. This makes Bayesian methodology appealing since it allows a natural way to exploit information from past studies. In the present paper, we suggest the use of previous data for constructing the prior distribution of the control effect parameter. Specifically, we consider a dynamic power prior that possibly allows to discount the level of borrowing in the presence of heterogeneity between past and current control data. The discount parameter of the prior is based on the Hellinger distance between the posterior distributions of the control parameter based, respectively, on historical and current data. We develop the methodology for comparing normal means and we handle the unknown variance assumption using MCMC. We also provide a simulation study to analyze the proposed test in terms of frequentist size and power, as it is usually requested by regulatory agencies. Finally, we investigate comparisons with some existing methods and we illustrate an application to a real case study. [ABSTRACT FROM AUTHOR]

Following a request from the European Commission, the Panel on Additives and Products or Substances used in Animal Feed (FEEDAP) was asked to deliver a scientific opinion on the efficacy of a feed additive consisting of carvacrol (Nimicoat®) as a zootechnical feed additive for weaned piglets at the recommended use level of 250 mg/kg complete feed. In a previous assessment, three efficacy trials and one tolerance–efficacy trial were assessed. Only one of the efficacy trials was considered to support the efficacy at the recommended use level. The applicant provided amendments to two previously submitted studies and a new trial. The amendments to the previously submitted studies did not change the conclusions from the previous assessment. The new efficacy study showed a significant improvement of the zootechnical parameters. Two studies showed positive and significant effects on the performance of the weaned piglets when the additive was administered at 250 mg/kg feed. Due to the lack of sufficient data, the FEEDAP Panel is not in the position to conclude on the efficacy of the additive for the target species. [ABSTRACT FROM AUTHOR]

This article explores a M/M/m unreliable retrial queue with reneging and diverse outgoing services. Incoming calls that arrive and discover all servers occupied join the orbit. The buffering incomings from the orbit retry their request after a while or leave the system without receiving service. When the orbit becomes empty, the idle server provides outgoing services. It is assumed that there are two categories of outgoing services. Due to unexpected circumstances, the server may breakdown. When a server undergoes breakdown, immediate repair process begins. Post-server breakdown, incoming calls go into orbit and retry service randomly, whereas the two variants of outgoing calls leave the system. The study utilizes a quasi-birth-death (QBD) process to analyse the stationary system size distribution. The steady state probabilities and the rate matrix are obtained through the matrix geometric method (MGM). Various performance metrics are evaluated for the proposed model. The study examines the impact of various system-based parameters on efficiency metrics with the help of numerical results. [ABSTRACT FROM AUTHOR]

Background: Adolescence is a period of heightened vulnerability to developing mental health problems, and rates of mental health disorder in this age group have increased in the last decade. Preventing mental health problems developing before they become entrenched, particularly in adolescents who are at high risk, is an important research and clinical target. Here, we report the protocol for the trial of the 'Building Resilience through Socioemotional Training' (ReSET) intervention. ReSET is a new, preventative intervention that incorporates individual-based emotional training techniques and group-based social and communication skills training. We take a transdiagnostic approach, focusing on emotion processing and social mechanisms implicated in the onset and maintenance of various forms of psychopathology. Methods: A cluster randomised allocation design is adopted with randomisation at the school year level. Five-hundred and forty adolescents (aged 12–14) will be randomised to either receive the intervention or not (passive control). The intervention is comprised of weekly sessions over an 8-week period, supplemented by two individual sessions. The primary outcomes, psychopathology symptoms and mental wellbeing, will be assessed pre- and post-intervention, and at a 1-year follow-up. Secondary outcomes are task-based assessments of emotion processing, social network data based on peer nominations, and subjective ratings of social relationships. These measures will be taken at baseline, post-intervention and 1-year follow-up. A subgroup of participants and stakeholders will be invited to take part in focus groups to assess the acceptability of the intervention. Discussion: This project adopts a theory-based approach to the development of a new intervention designed to target the close connections between young people's emotions and their interpersonal relationships. By embedding the intervention within a school setting and using a cluster-randomised design, we aim to develop and test a feasible, scalable intervention to prevent the onset of psychopathology in adolescence. Trial registration: ISRCTN88585916. Trial registration date: 20/04/2023. [ABSTRACT FROM AUTHOR]

The past decade has seen substantial innovation in clinical trials, including new trial formats, endpoints, and others. Also there have been regulatory changes, increasing competitive pressures and other external factors which impact clinical trials. In parallel, trial timelines have increased and success rates remain stubbornly low. This has led many observers to question whether clinical trials have become overly complex and if this complexity is always needed. Here we present a large-scale analysis of protocols and other data from over 16,000 trials. Using a machine learning algorithm, we automatically assessed key features of these trials, such as number of endpoints, number of inclusion–exclusion criteria and others. Using a regression analysis we combined these features into a new metric, the Trial Complexity Score, which correlates with overall clinical trial duration. Looking at this score across different clinical phases and therapeutic areas we see substantial increases over time, suggesting that clinical trials are indeed becoming more complex. We discuss drivers of increasing trial complexity, necessary or helpful ('good') complexity versus unnecessary ('bad') complexity, and we explore mechanisms of how sponsors of clinical trials can reduce trial complexity where appropriate. [ABSTRACT FROM AUTHOR]

Fewer than half of patients treated with hemodialysis survive 5 years. Multiple therapeutics are used to address the complications of advanced chronic kidney disease but most have not been found to improve clinical outcomes. Clinical trials of treatment innovations for chronic kidney diseases and dialysis care have been suboptimal in number and quality. Recent trials are changing this trend. Practice and policy change when new evidence emerges remains frequently impeded by resource and organizational constraints and accordingly, clinical practice guidelines are updated years or decades after definitive evidence is produced. Ultimately, practice change in health systems is slow, leading to impaired uptake of effective medical interventions and lower value healthcare, although innovations in rapid guideline production are emerging. What can be done to ensure that conclusive evidence is taken up in practice, policy and healthcare funding? We use the example of the recently published hard endpoint study "Comparison of high-dose HDF with high-flux HD" (CONVINCE) (hemodiafiltration versus hemodialysis), to explain how a new trial can impact on medical knowledge and change in practices. We (i) assess how the trial can be placed in the context of the totality of the evidence, (ii) define whether or not further trials of convective dialysis therapies are still needed and (iii) examine whether the evidence for convective therapies is now ready to inform practice, policy and funding change. When looking at CONVINCE in the context of the totality of evidence, we show that it addresses dialysis quality improvement priorities and is consistent with other trials evaluating convective dialysis therapies, and that the evidence for convective dialysis therapies is now definitive. Once updated evidence for cost-effectiveness in specific healthcare settings and patient-reported outcomes become available, we should therefore determine whether or not clinical practice guidelines should recommend uptake of convective dialysis therapies routinely, and move on to evaluating other treatments. [ABSTRACT FROM AUTHOR]

As artificial intelligence (AI) has been highly advancing in the last decade, machine learning (ML)-enabled medical devices are increasingly used in healthcare. In this study, we collected publicly available information on AI/ML-enabled medical devices approved by the FDA in the United States, as of the latest update on 19 October 2023. We performed comprehensive analysis of a total of 691 FDA-approved artificial intelligence and machine learning (AI/ML)-enabled medical devices and offer an in-depth analysis of clearance pathways, approval timeline, regulation type, medical specialty, decision type, recall history, etc. We found a significant surge in approvals since 2018, with clear dominance of the radiology specialty in the application of machine learning tools, attributed to the abundant data from routine clinical data. The study also reveals a reliance on the 510(k)-clearance pathway, emphasizing its basis on substantial equivalence and often bypassing the need for new clinical trials. Also, it notes an underrepresentation of pediatric-focused devices and trials, suggesting an opportunity for expansion in this demographic. Moreover, the geographical limitation of clinical trials, primarily within the United States, points to a need for more globally inclusive trials to encompass diverse patient demographics. This analysis not only maps the current landscape of AI/ML-enabled medical devices but also pinpoints trends, potential gaps, and areas for future exploration, clinical trial practices, and regulatory approaches. In conclusion, our analysis sheds light on the current state of FDA-approved AI/ML-enabled medical devices and prevailing trends, contributing to a wider comprehension. [ABSTRACT FROM AUTHOR]

Modern otology faces challenges in treating tympanic membrane (TM) perforations. Instead of surgical intervention, alternative treatments using biomaterials are emerging. Recently, we developed a robust collagen membrane using semipermeable barrier-assisted electrophoretic deposition (SBA-EPD). In this study, a collagen graft shaped like a sponge through SBA-EPD was used to treat acute and chronic TM perforations in a chinchilla model. A total of 24 ears from 12 adult male chinchillas were used in the study. They were organized into four groups. The first two groups had acute TM perforations and the last two had chronic TM perforations. We used the first and third groups as controls, meaning they did not receive the implant treatment. The second and fourth groups, however, were treated with the collagen graft implant. Otoscopic assessments were conducted on days 14 and 35, with histological evaluations and TM vibrational studies performed on day 35. The groups treated with the collagen graft showed fewer inflammatory changes, improved structural recovery, and nearly normal TM vibrational properties compared to the controls. The porous collagen scaffold successfully enhanced TM regeneration, showing high biocompatibility and biodegradation potential. These findings could pave the way for clinical trials and present a new approach for treating TM perforations. [ABSTRACT FROM AUTHOR]

Background: Requiring authors to base their research on a systematic review of the existing literature prevents the generation of redundant scientific studies, thereby avoiding the deprivation of effective therapies for trial participants and the waste of research funds. Scientific medical journals could require this in their author guidelines. While this applies to all areas of research, it is also relevant to physiotherapy and rehabilitation research, which predominantly involve interventional trials in patients. Objective: The aim of this study was to determine the extent to which the use of systematic reviews to justify a new trial is already being requested by physiotherapy-related scientific medical journals (PTJs). In addition, a comparison was made between PTJs and scientific medical journals with the highest impact factor in the Science Citation Index Extended (SCIE). Methods: This meta-research study is based on a systematic examination of the author guidelines of 149 PTJs. The journals were identified and included based on the number of publications with physiotherapy as a keyword in the databases PEDro, and Medline (Pubmed). The included author guidelines were analysed for the extent to which they specified that a new trial should be justified by a systematic review of the literature. Additionally, they were compared with 14 scientific medical journals with the highest impact factor in the SCIE (LJs). Results: In their author guidelines, none of the included PTJs required or recommended the use of a systematic review to justify a new trial. Among LJs, four journals (28.57%), all associated with the Lancet group, required the study justification through a systematic review of the literature. Conclusion: Neither PTJs nor LJs require or recommend the use of a systematic review to justify a new trial in their author guidelines. This potentially leaves room for unethical scientific practices and should be critically considered in future research. [ABSTRACT FROM AUTHOR]

Background: The new European Medicines Agency (EMA) Clinical Trials Information System (CTIS), based on the Clinical Trials Regulation (CTR EU 536/2014), came into full effect on 31 January 2022 and was intended to provide an easier, more streamlined approach to the registration of clinical trials taking place in Europe. Using the experience gained on the new regulatory framework from three multi-national European clinical research studies of outbreak-prone infectious diseases, this article describes the advantages and shortcomings of the new clinical trial submission procedure. Methods: We report the time to approval, size of the application dossier, and number of requests for information (RFIs) for each study. We also explore the experience of each study within the regulatory framework and its use of CTIS to document the real-world, practical consequences of the system on individual studies. The study assesses the experience of three multi-country studies conducted in Europe working within the EU and non-EU regulatory environments. Results: While the time to regulatory and ethical approval has improved since the implementation of the new regulation, the timelines for approvals are still unacceptably slow, particularly for studies being conducted in the context of an evolving outbreak. Within the new regulatory approval procedure, there is evidence of conflicting application requirements, increased document burden, barriers to submitting important modifications, and debilitating technical hurdles. Conclusions: CTIS promised to lower the administrative bar, but unfortunately this has not been achieved. There are challenges that need to be urgently confronted and addressed for international research collaborators to effectively manage health crises in the future. While the value of multi-national outbreak research is clear, the limitations and delays imposed by the system, which raise challenging ethical questions about the regulation, are prejudicial to all clinical research, especially publicly funded academic studies. This report is relevant to both regulators and clinical researchers. It is hoped that these findings can help improve pan-European clinical trials, especially for the purpose of epidemic preparedness and response. Trial registration: This paper references experiences gained during management of three pan-European trials: EU-SolidAct's Bari-SolidAct (CT No. 2022-500385-99-00 - 15 March 2022) and AXL-SolidAct (CT No. 2022-500363-12-00 - 19 April 2022), and MOSAIC (CT No. 2022-501132-42-00 - 22 June 2022). [ABSTRACT FROM AUTHOR]

How many times can a defendant be retried? For those facing hung jury retrials, it's as many times as the government pleases. Double jeopardy prohibitions do not apply when juries fail to reach a verdict. There is, theoretically, a built-in procedural solution to stop the government from endlessly retrying defendants. Rule 29 of the Federal Rules of Criminal Procedure allows judges to acquit defendants when "the evidence is insufficient to sustain a conviction." Considering that a hung jury indicates the jurors could not agree on the sufficiency of the evidence, defendants facing hung jury retrials are prime candidates for this Rule's application. Yet Rule 29 has not been applied to prevent hung jury retrials. Instead, the Supreme Court has given a government-biased standard for deciding whether there is insufficient evidence to convict, stating that a judge must consider the evidence in the "light most favorable" to the government. This standard, which can force judges to nonsensically conduct the same analysis in perpetuity when juries repeatedly indicate that evidence is insufficient to convict, is not a functional standard. This Note proposes a new post-hung jury Rule 29 standard. Rather than viewing the evidence in the light most favorable to the government, a judge should view the evidence in the light it was actually viewed by the hung jury, with no bias toward the government. Doing so allows a judge to consider a jury's inability to reach a verdict as proof that the evidence is insufficient, preventing the government from unduly retrying cases where multiple juries have failed to convict. Moreover, a Rule 29 acquittal cannot be appealed, meaning this new standard can be applied today even without the approval of appellate courts. [ABSTRACT FROM AUTHOR]

Searching for trials is a key task in systematic reviews and a focus of automation. Previous approaches required knowing examples of relevant trials in advance, and most methods are focused on published trial articles. To complement existing tools, we compared methods for finding relevant trial registrations given a International Prospective Register of Systematic Reviews (PROSPERO) entry and where no relevant trials have been screened for inclusion in advance. We compared SciBERT‐based (extension of Bidirectional Encoder Representations from Transformers) PICO extraction, MetaMap, and term‐based representations using an imperfect dataset mined from 3632 PROSPERO entries connected to a subset of 65,662 trial registrations and 65,834 trial articles known to be included in systematic reviews. Performance was measured by the median rank and recall by rank of trials that were eventually included in the published systematic reviews. When ranking trial registrations relative to PROSPERO entries, 296 trial registrations needed to be screened to identify half of the relevant trials, and the best performing approach used a basic term‐based representation. When ranking trial articles relative to PROSPERO entries, 162 trial articles needed to be screened to identify half of the relevant trials, and the best‐performing approach used a term‐based representation. The results show that MetaMap and term‐based representations outperformed approaches that included PICO extraction for this use case. The results suggest that when starting with a PROSPERO entry and where no trials have been screened for inclusion, automated methods can reduce workload, but additional processes are still needed to efficiently identify trial registrations or trial articles that meet the inclusion criteria of a systematic review. [ABSTRACT FROM AUTHOR]

Leukodystrophies are a heterogeneous group of rare genetic disorders primarily affecting the white matter of the central nervous system. These conditions can present a diagnostic challenge, requiring a comprehensive approach that combines clinical evaluation, neuroimaging, metabolic testing, and genetic testing. While MRI is the main tool for diagnosis, advances in molecular diagnostics, particularly whole-exome sequencing, have significantly improved the diagnostic yield. Timely and accurate diagnosis is crucial to guide symptomatic treatment and assess eligibility to participate in clinical trials. Despite no specific cure being available for most leukodystrophies, gene therapy is emerging as a potential treatment avenue, rapidly advancing the therapeutic prospects in leukodystrophies. This review will explore diagnostic and therapeutic strategies for leukodystrophies, with particular emphasis on new trials. [ABSTRACT FROM AUTHOR]

Resistant hypertension (RH) is linked to an increased risk of cardiovascular and renal complications. Treatment options include non-pharmacological interventions, such as lifestyle modifications, and the use of specific antihypertensive drug combinations, including diuretics. Renal denervation is another option for treatment-resistant hypertension. New compounds targeting different pathways involved in RH—including inhibitors of aminopeptidase A, endothelin antagonists and selective aldosterone synthase inhibitors—have been tested in clinical trials in this condition. The centrally acting drug firibastat, targeting the brain renin–angiotensin system, failed to demonstrate significant effectiveness in reducing blood pressure (BP) in patients with difficult-to-treat and RH in the Firibistat in Resistant Hypertension (FRESH) trial. Aprocitentan, a dual endothelin A and B receptor antagonist, showed a moderate but statistically significant decrease in BP in patients with RH in the Parallel-Group, Phase 3 Study with Aprocitentan in Subjects with Resistant Hypertension (PRECISION) trial. However, concerns remain about potential adverse events, such as fluid retention. The use of baxdrostat, a selective aldosterone synthase inhibitor, showed promising results in reducing BP in patients with treatment-resistant hypertension in the Baxdrostat in Resistant Hypertension (BrigHTN) trial. However, a subsequent trial, HALO, failed to meet its primary endpoint. The unexpected results may be influenced by factors such as patient adherence and white-coat hypertension. Despite the disappointing results from HALO, the potential benefits of inhibiting aldosterone synthesis remain to be fully understood. In conclusion, managing RH remains challenging, and new compounds like firibastat, aprocitentan and baxdrostat have shown varied effectiveness. Further research is needed to improve our understanding and treatment of this condition. [ABSTRACT FROM AUTHOR]

The results of the exams that are carried out in the clinical laboratory should constitute an essential part in the evaluation of people included in clinical trials for the introduction of new medications. In this article the most important aspects of work in the laboratory are described, during the development of a trial where new technologies are used. Clinical trials not only improve health indicators of the population, but also, demand the best diagnosis standards and evaluation of the treatment, through new technologies, where clinical laboratory is included. [ABSTRACT FROM AUTHOR]

• AI and other predictive models are becoming increasingly common in criminal law. • Some decisions made by judges show high levels of predictability. • All predictions on petitions for new criminal trials in Sweden in 2021 were accurate. • Other types of legal decisions e.g. legal precedent are probably less predictable. Predictability of legal decisions is usually considered a prerequisite for the rule of law, following the maxim 'like cases should be treated alike'. Yet, this presupposes that the case outcome can be predicted based on the merits of the case, rather than other factors. The purpose of this study was to test whether and to what extent legal decisions on petitions for new criminal trials can be predicted on the basis of other fairly superficial criteria that one could access without even reading the case file, e.g. which Court decided, whether the applicant had legal representation etc. To this end, all petitions for new criminal trials submitted to the Swedish Supreme Court and the six Courts of Appeal in the time period 2010–2020 (n = 3915) were reviewed. This data formed the basis of a regression model which was then used to predict decisions regarding petitions in 2021. On the basis of access to legal representation and crime type, the regression model predicted accurately 100 % of the decisions made in 2021. This raises questions about the evidentiary basis for the decisions and also the role of judges in situations where their decisions are fully predictable. [ABSTRACT FROM AUTHOR]

We study the effect of "nudges" on taxpayers who have varying tax-compliance histories in Papua New Guinea. We present the results from two population-wide randomized controlled trials conducted in a setting that is characterized by low compliance rates and a lack of effective enforcement. We test the effect of text messages, flyers, and emails that remind taxpayers of declaration due dates and provide information about the public benefits of paying taxes. We find that the treatments increased the number of tax declarations filed without increasing the amount of tax paid because the taxpayers who responded to the nudges reported a tax liability of zero. This result is consistent across tax types, communication channels, and time periods. We also find that the treatments had no effect on previously nonfiling taxpayers. Collectively, our results illustrate that taxpayers who face the lowest cost of compliance are the most likely to respond to a nudge. [ABSTRACT FROM AUTHOR]

The retrial phenomenon occurs inherently in a wide range of queueing systems. The majority of retrial queueing models do not account for vacation. However, in practice, retrial queueing systems undergo vacations for maintenance or other reasons. In this study, we provide an in-depth analysis of the many possible retrial queueing systems when Bernoulli vacations are in effect. Moreover, this study outlines the key principles and reviews the relevant literature. The framework of a retrial queue with Bernoulli vacation has numerous applications in computer networking systems, manufacturing and production mechanisms, inventory systems, including network service, mail service and file transfer service, etc. Several retrial queueing systems have been investigated, notably M/M/1, M/M/C, M/G/1, M[X]/G/1, and Geo/G/1. Many other important situations, such as server interruption, feedback, G-queue, impatient customers, priority customers, etc., have been explored in relation to retrial queues with Bernoulli vacation and the results of these investigations are also highlighted. The foremost objective of this study is to help researchers, administrators and technical workers who want to use queuing theory to simulate congestion and need to know where to find details on the right models. Finally, some open problems and potential future lines of survey are also covered. [ABSTRACT FROM AUTHOR]