Nonlinear mixed models and related approaches in infectious disease modeling: A systematic and critical review.

The level of surveillance and preparedness against epidemics varies across countries, resulting in different responses to outbreaks. When conducting an in-depth analysis of microinfection dynamics, one must account for the substantial heterogeneity across countries. However, many commonly used statistical model specifications lack the flexibility needed for sound and accurate analysis and prediction in such contexts. Nonlinear mixed effects models (NLMMs) constitute a specific statistical tool that can overcome these significant challenges. While compartmental models are well-established in infectious disease modeling and have seen significant advancements, Nonlinear Mixed Models (NLMMs) offer a flexible approach for handling heterogeneous and unbalanced repeated measures data, often with less computational effort than some individual-level compartmental modeling techniques. This study provides an overview of their current use and offers a solid foundation for developing guidelines that may help improve their implementation in real-world situations. Relevant scientific databases in the Research4life Access initiative programs were used to search for papers dealing with key aspects of NLMMs in infectious disease modeling (IDM). From an initial list of 3641 papers, 124 were finally included and used for this systematic and critical review spanning the last two decades, following the PRISMA guidelines. NLMMs have evolved rapidly in the last decade, especially in IDM, with most publications dating from 2017 to 2021 (83.33%). The routine use of normality assumption appeared inappropriate for IDM, leading to a wealth of literature on NLMMs with non-normal errors and random effects under various estimation methods. We noticed that NLMMs have attracted much attention for the latest known epidemics worldwide (COVID-19, Ebola, Dengue and Lassa) with the robustness and reliability of relaxed propositions of the normality assumption. A case study of the application of COVID-19 data helped to highlight NLMMs' performance in modeling infectious diseases. Out of this study, estimation methods, assumptions, and random terms specification in NLMMs are key aspects requiring particular attention for their application in IDM.

Uso da adaptação transcultural nos cursos de pós-graduação em Enfermagem / Use of cross-cultural adaptation in Postgraduate Nursing courses / Uso de la adaptación transcultural en las carreras de grado en Enfermería

Objetivo: analisar a produção científica brasileira, na Pós-Graduação em Enfermagem, que utilizou o método de adaptação transcultural. Método: estudo documental, com busca realizada na Biblioteca Digital de Teses e Dissertações, que resultou em 140 dissertações e 72 teses para análise, oriundas de Programas de Pós-Graduação da região Sudeste, seguida das regiões Nordeste, Sul e Centro-Oeste, sem representação da região Norte. Resultados: os instrumentos adaptados foram, em sua maioria, procedentes do idioma inglês. Prevaleceram as pesquisas na área/campo Assistencial, destacando-se a linha de pesquisa Processo de Cuidar em Saúde e Enfermagem. Identificou-se descompasso entre o que é produzido na área e o que é recomendado internacionalmente. Conclusão: verificou-se aumento na utilização da adaptação transcultural como método de pesquisa, com persistência das assimetrias acadêmicas regionais e sem consenso sobre o referencial metodológico.

Objective: to analyze the Brazilian scientific production in Postgraduate Nursing education using the cross-cultural adaptation method. Method: documentary study with searches carried out in the Digital Library of Theses and Dissertations resulting in 140 Master's theses and 72 Doctoral dissertations for analysis originated from Postgraduate Programs carried out in the Southeast region of Brazil, followed by the Northeast, South and Midwest regions ­ there was no representation of the North region. Results: the adapted instruments were, mostly, originally written in English. Research in the Care area/field prevailed, highlighting the line of research called Health and Nursing Care Process. A gap between what is produced in the area and what is recommended internationally was identified. Conclusion: an increase in the use of cross-cultural adaptation as a research method was noticed, with the persistence of regional academic asymmetries and lack of consensus on the methodological framework.

Objetivo: analizar la producción científica brasileña, en el Postgrado en Enfermería, que utilizó el método de adaptación transcultural. Método: estudio documental, la búsqueda se realizó en la Biblioteca Digital de Tesis y Disertaciones, se obtuvieron 140 tesis de maestría y 72 tesis de doctorado para análisis, provenientes de Programas de Posgrado de la región Sudeste, seguida de las regiones Nordeste, Sur y Centro-Oeste, no se encontraron documentos de la región Norte. Resultados: los instrumentos adaptados fueron, en su mayoría, del idioma inglés. Predominaron las investigaciones en el área/campo Asistencial, se destacó la línea de investigación Proceso de Atención en Salud y Enfermería. Se identificó que lo que se produce en el área no coincide con lo que se recomienda a nivel internacional. Conclusión: se comprobó que aumentó el uso de la adaptación transcultural como método de investigación, que persisten las disparidades académicas regionales y que no hay consenso sobre el marco metodológico.

Efficacy of Social Norm Interventions on Addictive Behaviours-A Systematic Review and Meta-Analysis of Randomised Controlled Trials.

Mental health-related behaviours including addictive behaviours contribute significantly to the global burden of disease. Social norm interventions appear to be a cost-effective means of reducing addictive behaviour. We conducted a systematic review and meta-analysis of the efficacy of social norm interventions for addictive behaviours. We searched the databases Medline and PsycInfo from inception to April 2024 as well as reference lists of eligible studies and related systematic reviews for randomised controlled trials (RCTs) comparing the efficacy of social norm interventions for addictive behaviours to control conditions. Out of the 11,515 potentially eligible RCTs, 52 trials with a total of 31,764 adult participants met inclusion criteria, with 45 trials targeting alcohol consumption, three trials targeting Marijuana use, two trials targeting other substance abuse and two trials targeting gambling. Overall, 37 trials were included in the random-effects meta-analysis. The comparison of social norm interventions to control conditions at posttreatment showed a small but statistically significant effect (g = -0.12; 95% CI = -0.22 to -0.02; p < 0.01). Risk of bias was rated low in 37 RCTs, 14 RCTs were rated as having some risk of bias concerns and one RCT was rated as having high risk of bias. Social norm interventions can be an effective intervention method for reducing substance abuse and gambling. Yet, data is largely derived from studies targeting alcohol consumption and current trials suffer from methodological and practical limitations. The small effect sizes need to be appraised in the context of cost-effectiveness of these interventions.

Pangenome comparison via ED strings.

Introduction: An elastic-degenerate (ED) string is a sequence of sets of strings. It can also be seen as a directed acyclic graph whose edges are labeled by strings. The notion of ED strings was introduced as a simple alternative to variation and sequence graphs for representing a pangenome, that is, a collection of genomic sequences to be analyzed jointly or to be used as a reference. Methods: In this study, we define notions of matching statistics of two ED strings as similarity measures between pangenomes and, consequently infer a corresponding distance measure. We then show that both measures can be computed efficiently, in both theory and practice, by employing the intersection graph of two ED strings. Results: We also implemented our methods as a software tool for pangenome comparison and evaluated their efficiency and effectiveness using both synthetic and real datasets. Discussion: As for efficiency, we compare the runtime of the intersection graph method against the classic product automaton construction showing that the intersection graph is faster by up to one order of magnitude. For showing effectiveness, we used real SARS-CoV-2 datasets and our matching statistics similarity measure to reproduce a well-established clade classification of SARS-CoV-2, thus demonstrating that the classification obtained by our method is in accordance with the existing one.

Cross-species comparison of airway epithelium transcriptomics.

Studies of lung transcriptomics across species are essential for understanding the complex biology and disease mechanisms of this vital organ. Single-cell RNA sequencing (scRNA-seq) has emerged as a key tool for understanding cell dynamics across various species. However, comprehensive cross-species comparisons are limited. Therefore, the aims of this study was to investigate the transcriptomic similarities and differences in lung cells across four species-humans, monkeys, mice, and rats-in healthy and asthma conditions using scRNA-seq. The results revealed significant transcriptomic similarities between monkeys and humans and significant cross-species conservation of cell-specific marker genes, transcription factors (TFs), and biological pathways. Additionally, we explored sex differences, identifying distinct sex-specific expression patterns that may influence disease susceptibility. These insights refine our understanding of the mechanism underlying airway cell biology across species and have important implications for studying lung diseases, particularly the mechanisms of mucus clearance in asthma.

A Comparative Study Between Coblation-Assisted Tonsillectomy and Conventional Dissection and Snare Tonsillectomy.

Background Tonsillitis is a vastly prevalent disease, accounting for the majority of outpatient visits. The dissection and snare method has been the predominant approach for tonsillectomy for centuries. Coblation-assisted tonsillectomy offers advantages such as faster healing, shorter surgery duration, minimal blood loss, and fewer postoperative complications. Therefore, a study was conducted to evaluate the distinctions and compare the efficacy of traditional dissection and coblation-assisted tonsillectomy. Materials and methods Patients were divided into two groups: Group I was operated on using the conventional method, and Group II was operated on using the coblation method. Both groups were then assessed for intraoperative time, intraoperative bleeding, postoperative pain, and postoperative complications. Results Coblation-assisted tonsillectomy patients had a significantly shorter mean duration for the procedure and significantly lower blood loss in comparison to the conventional method. There were no statistically significant variations in the incidence of postoperative complications. Coblation-assisted tonsillectomy patients experienced considerably higher pain scores on various postoperative days. Conclusion Coblation-assisted tonsillectomy had the added advantage of reduced intraoperative blood loss, shorter surgical time, and faster recovery postoperatively. Coblation-assisted tonsillectomy can be considered an effective alternative to conventional methods. However, it's important to consider factors such as cost-effectiveness and surgeon experience. Further research involving larger sample sizes and longer follow-up periods could yield more insightful knowledge of the outcomes of these two tonsillectomy techniques.

Multidimensional Care Poverty Among East Asian and Nordic Older Adults.

Background and Objectives: This study uses the care poverty framework, focusing on both individuals and structures. In this context, structures are represented by 2 welfare states: Taiwan, an East Asian welfare system and Finland, a Nordic welfare state. This study explores multidimensional care poverty rates and examines 3 realms of individual factors (health status, sociodemographic factors, and care support availability) among older adults in these long-term care (LTC) models. Research Design and Methods: We analyzed data from the 2019 Taiwan Longitudinal Study on Ageing Survey and the 2020 Daily Life and Care in Old Age Survey in Finland to compare the rates and factors of care poverty in these 2 culturally and structurally different countries. Results: Our analysis revealed different rates of care poverty in personal, practical, and socioemotional care needs in the 2 countries. Under a familistic welfare regime, Taiwanese older adults had higher personal care poverty rates than their Finnish counterparts. Those living alone faced more personal and practical care poverty. Conversely, Finnish older adults, under the Nordic welfare model, experienced more practical and socioemotional care poverty. Those with high care needs and disadvantaged social status and support were more likely to experience personal and practical care poverty. Socioemotional care poverty varied with the availability of support and health status in both countries. Discussion and Implications: The study highlights the impact of 2 LTC policies and cultures on older adults' multidimensional care poverty, identifying disadvantaged older adults under different welfare-transforming LTC models. Taiwan's budget-constrained LTC policies and high family reliance contrast with Finland's inadequate attention to the practical and socioemotional needs of its aging population. This study suggests that holistic LTC policies are needed in both countries to improve the well-being of older adults with limited support and health issues.

Optimizing emergency department efficiency: a comparative analysis of process mining and simulation models to mitigate overcrowding and waiting times.

OBJECTIVE: Overcrowding and extended waiting times in emergency departments are a pervasive issue, leading to patient dissatisfaction. This study aims to compare the efficacy of two process mining and simulation models in identifying bottlenecks and optimizing patient flow in the emergency department of Al-Zahra Hospital in Isfahan. The ultimate goal is to reduce patient waiting times and alleviate population density, ultimately enhancing the overall patient experience. METHODS: This study employed a descriptive, applied, cross-sectional, and retrospective design. The study population consisted of 39,264 individuals referred to Al-Zahra Hospital, with a sample size of at least 1,275 participants, selected using systematic random sampling at a confidence level of 99%. Data were collected through a questionnaire and the Hospital Information System (HIS). Statistical analysis was conducted using Excel software, with a focus on time-averaged data. Two methods of simulation and process mining were utilized to analyze the data. First, the model was run 1000 times using ARENA software, with simulation techniques. In the second step, the emergency process model was discovered using process mining techniques through Access software, and statistical analysis was performed on the event log. The relationships between the data were identified, and the discovered model was analyzed using the Fuzzy Miner algorithm and Disco tool. Finally, the results of the two models were compared, and proposed scenarios to reduce patient waiting times were examined using simulation techniques. RESULTS: The analysis of the current emergency process at Al-Zahra Hospital revealed that the major bottlenecks in the process are related to waiting times, inefficient implementation of doctor's orders, delays in recording patient test results, and congestion at the discharge station. Notably, the process mining exercise corroborated the findings from the simulation, providing a comprehensive understanding of the inefficiencies in the emergency process. Next, 34 potential solutions were proposed to reduce waiting times and alleviate these bottlenecks. These solutions were simulated using Arena software, allowing for a comprehensive evaluation of their effectiveness. The results were then compared to identify the most promising strategies for improving the emergency process. CONCLUSION: In conclusion, the results of this research demonstrate the effectiveness of using simulation techniques and process mining in making informed, data-driven decisions that align with available resources and conditions. By leveraging these tools, unnecessary waste and additional expenses can be significantly reduced. The comparative analysis of the 34 proposed scenarios revealed that two solutions stood out as the most effective in improving the emergency process. Scenario 19, which involves dedicating two personnel to jointly referring patients to the ward, and scenario 34, which creates a dedicated discharge hall, have the potential to create a more favorable situation.

Efficacy and Safety of Intravenous Diltiazem Versus Metoprolol in the Management of Atrial Fibrillation with Rapid Ventricular Response in the Emergency Department: A Comprehensive Umbrella Review of Systematic Reviews and Meta-analyses.

Atrial fibrillation (AF) is the most common cardiac arrhythmia in the United States, affecting 2.7-6.1 million people. AF can cause symptoms, but when it triggers a rapid ventricular response (RVR), most patients suffer from decompensation. Therefore, we performed an umbrella review of systematic reviews and meta-analyses comparing intravenous (IV) metoprolol and diltiazem to identify discrepancies, fill in knowledge gaps, and develop standardized decision-making guidelines for physicians to manage AF with RVR. A comprehensive search was conducted in PubMed, the Cochrane Library, and Scopus to identify studies for this umbrella review. The overall certainty of the evidence was assessed using the Grading of Recommendations Assessment, Development, and Evaluation method, while the quality of the included reviews was evaluated using AMSTAR 2, the Cochrane Collaboration tool, and the Newcastle-Ottawa scale. This study comprehensively analyzed four meta-analyses covering 11 randomized controlled trials and 19 observational studies. The analysis showed that IV diltiazem treatment was significantly more successful in rate control for AF with rapid ventricular response (RVR) than IV metoprolol (risk ratio [RR], 1.30; 95% confidence interval [CI], 1.09-1.56; I 2 = 0%; P = .003). IV diltiazem also led to a significantly greater reduction in ventricular rate (mean difference, -14.55; 95% CI, -16.93 to -12.16; I 2 = 72%; P < .00001), particularly at 10 min. The analysis also revealed a significantly increased risk of hypotension associated with treatment with IV diltiazem (RR, 1.43; 95% CI, 1.14-1.79; I 2 = 0%; P = .002). In conclusion, IV diltiazem therapy achieved better rate control and ventricular rate decrease than metoprolol therapy in AF with RVR. Future clinical trials should compare calcium channel blockers and ß-blockers for heart rate control efficacy and safety, considering adverse events.

Comparison of Nucleotide MALDI-TOF MS with Xpert MTB/RIF for Rifampicin Susceptibility Identification and Associated Risk Factors of Rifampicin Resistance Among Drug Resistant Mycobacterium tuberculosis.

Purpose: Nucleotide-based matrix-assisted laser desorption ionization time-of-flight mass spectrometry (nucleotide MALDI-TOF MS) is an emerging molecular technology used for the diagnosis of tuberculosis (TB) caused by Mycobacterium tuberculosis (MTB)and its drug resistance. This study aimed to compare the ability of nucleotide MALDI-TOF MS to detect rifampicin (RIF) resistance in drug-resistant TB (DR-TB) patients with Xpert MTB/RIF and to analyze the disparate results individually. Additionally, potential factors associated with rifampicin resistance among DR-TB patients in Qingdao were investigated. Patients and Methods: A retrospective study was conducted at Qingdao Chest Hospital, and patients with DR-TB were enrolled. Corresponding frozen isolates were recovered and subjected to nucleotide MALDI-TOF MS, Xpert MTB/RIF, and phenotypic drug susceptibility testing (pDST). Sanger sequencing was performed for the discordant results of nucleotide MALDI-TOF MS and Xpert MTB/RIF. Univariate and multivariate logistic regression analyses were used to identify potential factors associated with rifampicin resistance among patients with DR-TB. Results: A total of 125 patients with DR-TB (18.8%, 125/668) were enrolled in this study from May 1 to July 31, 2023. Rifampicin-resistant (DR-TB/RR, 29) and rifampicin-sensitive (DR-TB/RS, 96) groups were divided according to the pDST results. Nucleotide MALDI-TOF MS performed better than Xpert MTB/RIF in terms of sensitivity, specificity, accuracy, and agreement with pDST. Only six cases had inconsistent results, and the sequencing results of five cases were identical to nucleotide MALDI-TOF MS. Furthermore, chest pain (aOR=12.84, 95% CI, 2.29-91.97, p=0.005), isoniazid sensitivity (aOR=0.14, 0.02-0.59, p=0.013), and ethambutol sensitivity (aOR=0.02, 0.00-0.10, p=0.000) were potential factors associated with rifampicin resistance among DR-TB patients in Qingdao. Conclusion: The overall concordance between nucleotide MALDI-TOF MS and Xpert MTB/RIF was 95.2%, with the former performing better in determining rifampicin susceptibility among DR-TB cases in Qingdao. Chest pain, isoniazid, and ethambutol resistance might be factors associated with RIF resistance among patients with DR-TB in Qingdao.

Midlife health in Britain and the United States: a comparison of two nationally representative cohorts.

BACKGROUND: Older adults in the USA have worse health and wider socioeconomic inequalities in health compared with those in Britain. Less is known about how health in the two countries compares in mid-life, a time of emerging health decline, including inequalities in health. METHODS: We compare measures of current regular smoking status, obesity, self-rated health, cholesterol, blood pressure and glycated haemoglobin using population-weighted modified Poisson regression in the 1970 British Cohort Study (BCS70) in Britain (N = 9665) and the National Longitudinal Study of Adolescent to Adult Health (Add Health) in the USA (N = 12 300), when cohort members were aged 34-46 and 33-43, respectively. We test whether associations vary by early- and mid-life socioeconomic position. RESULTS: US adults had higher levels of obesity, high blood pressure and high cholesterol. Prevalence of poor self-rated health and current regular smoking was worse in Britain. We found smaller socioeconomic inequalities in mid-life health in Britain compared with the USA. For some outcomes (e.g. smoking), the most socioeconomically advantaged group in the USA was healthier than the equivalent group in Britain. For other outcomes (hypertension and cholesterol), the most advantaged US group fared equal to or worse than the most disadvantaged groups in Britain. CONCLUSIONS: US adults have worse cardiometabolic health than British counterparts, even in early mid-life. The smaller socioeconomic inequalities and better overall health in Britain may reflect differences in access to health care, welfare systems or other environmental risk factors.

Robotic female artificial urinary sphincter implantation vs. male artificial urinary sphincter implantation for non-neurogenic stress urinary incontinence.

PURPOSE: Previous studies suggested better functional outcomes and longer device survival for female artificial urinary sphincter (AUS) implantation compared to male AUS implantation. We hypothesized that the adoption of robotic approaches for female implantation might have influenced these comparisons. This study aimed to compare the outcomes of robotic female AUS and male AUS implantation for non-neurogenic stress urinary incontinence (SUI). METHODS: We retrospectively reviewed charts of male patients who had AUS implantation and female patients who underwent robotic AUS implantation for non-neurogenic SUI between 2010 and 2022 at a single center. Prior AUS implantations were exclusion criteria. The primary endpoint was continence status at 3 months, categorized as complete resolution of SUI (0 pad), improved SUI (1pad), or unchanged SUI (>1pad). RESULTS: After excluding 79 patients, 171 were included: 70 women and 101 men. Operative time was shorter in males (126.9 vs. 165.5 min; p < 0.0001). Postoperative complication rates were similar (17.3% vs. 22.9%; p = 0.38). Continence status at 3 months and last follow-up favored females. The ICIQ-SF decrease at 3 months was greater in females (-7.2 vs. -4.6; p < 0.001). The 5-year estimated explantation-free survival was similar (78.6% vs. 73.7%; p = 0.94) as was the revision-free survival (67.4% vs. 61.7%; p = 0.89). Multivariate analysis showed that female gender was associated with better continence at last follow-up (OR = 4.3; p = 0.03). CONCLUSION: Robotic female AUS implantation is associated with better functional outcomes than male AUS implantation, with similar morbidity and survival rates.

Reproducibility of spatial penalty-based methodologies for intravoxel incoherent motion analysis with diffusion MRI.

Objective was to assess the precision and reproducibility of spatial penalty-based intravoxel incoherent motion (IVIM) methods in comparison to the conventional bi-exponential (BE) model-based IVIM methods. IVIM-MRI (11 b-values; 0-800 s/mm2) of forty patients (N = 40; Age = 17.7 ± 5.9 years; Male:Female = 30:10) with biopsy-proven osteosarcoma were acquired on a 1.5 Tesla scanner at 3 time-points: (i) baseline, (ii) after 1-cycle and (iii) after 3-cycles of neoadjuvant chemotherapy. Diffusion coefficient (D), Perfusion coefficient (D*) and Perfusion fraction (f) were estimated at three time-points in whole tumor and healthy muscle tissue using five methodologies (1) BE with three-parameter-fitting (BE), (2) Segmented-BE with two-parameter-fitting (BESeg-2), (3) Segmented-BE with one-parameter-fitting (BESeg-1), (4) BE with adaptive Total-Variation-penalty (BE + TV) and (5) BE with adaptive Huber-penalty (BE + HPF). Within-subject coefficient-of-variation (wCV) and between-subject coefficient-of-variation (bCV) of IVIM parameters were measured in healthy and tumor tissue. For precision and reproducibility, intra-scan comparison of wCV and bCV among five IVIM methods were performed using Friedman test followed by Wilcoxon-signed-ranks (WSR) post-hoc test. Experimental results demonstrated that BE + TV and BE + HPF showed significantly (p < 10-3) lower wCV and bCV for D (wCV: 24-32%; bCV: 22-31%) than BE method (wCV: 38-49%; bCV: 36-46%) across three time-points in healthy muscle and tumor. BE + TV and BE + HPF also demonstrated significantly (p < 10-3) lower wCV and bCV for estimating D* (wCV: 89-108%; bCV: 83-102%) and f (wCV: 55-60%; bCV: 56-60%) than BE, BESeg-2 and BESeg-1 methods (D*-wCV: 102-122%; D*-bCV: 98-114% and f-wCV: 96-130%; f-bCV: 94-125%) in both tumor and healthy tissue across three time-points. Spatial penalty based IVIM analysis methods BE + TV and BE + HPF demonstrated lower variability and improved precision and reproducibility in the current clinical settings.

Jointly benchmarking small and structural variant calls with vcfdist.

In this work, we extend vcfdist to be the first variant call benchmarking tool to jointly evaluate phased single-nucleotide polymorphisms (SNPs), small insertions/deletions (INDELs), and structural variants (SVs) for the whole genome. First, we find that a joint evaluation of small and structural variants uniformly reduces measured errors for SNPs (- 28.9%), INDELs (- 19.3%), and SVs (- 52.4%) across three datasets. vcfdist also corrects a common flaw in phasing evaluations, reducing measured flip errors by over 50%. Lastly, we show that vcfdist is more accurate than previously published works and on par with the newest approaches while providing improved result interpretability.

Deep Sequencing and Phenotyping in an Australian Tuberous Sclerosis Complex "No Mutations Identified" Cohort.

Tuberous sclerosis complex (TSC) is a variable multisystem disorder. The "no mutations identified" (NMI) group are reportedly phenotypically milder than those with an identified molecular cause, and often have mosaic or intronic variants not detected by standard sequencing methods. METHODS: We describe the phenotypes in an Australian TSC NMI group (n = 18) and a molecular testing strategy implementable in a diagnostic laboratory. Massively parallel sequencing (MPS) of the whole genomic regions of TSC1 and TSC2 was performed using DNA extracted from multiple tissue samples per participant. RESULTS: Our study showed that the phenotype in TSC NMI individuals can be similar to those with heterozygous, particularly TSC1, variants. Although neurodevelopmental outcomes can be less severe, the number of organ systems involved was similar to the non-mosaic groups. A diagnostic yield of 72% (13/18) was achieved, with the majority (10/13) being mosaic variants and the remainder heterozygous variants missed on previous testing. CONCLUSION: Testing DNA from multiple tissue samples allowed for validation of otherwise discarded low-level mosaic variants and detection of mosaic variants by MPS without excessive cost or the need for specialised techniques. Implementing this approach in a diagnostic setting is viable and allows optimal clinical care of patients with NMI TSC.

Comparison of Ultrasound-guided Transverse Carpal Ligament Release via Different Approaches in Carpal Tunnel Syndrome: A Prospective, Randomized, Controlled Trial.

BACKGROUND: Ultrasound-guided transverse carpal ligament (TCL) needle release has been demonstrated to be an effective treatment for carpal tunnel syndrome (CTS). However, no existing evidence has investigated the comparative efficacy of different release approaches. OBJECTIVE: To compare the efficacy of ultrasound-guided TCL needle release via different approaches for patients with mild to moderate CTS over a 12-month follow-up. STUDY DESIGN: A prospective, randomized, controlled trial. SETTING: Outpatient clinic at a university hospital. METHODS: Sixty-four patients with mild to moderate CTS (> 3 months' duration) were randomly assigned to either the long-axis group (one session of ultrasound-guided corticosteroid injection plus long-axis TCL needle release) or the short-axis group (one session of ultrasound-guided corticosteroid injection plus short-axis TCL needle release) in a one-to-one ratio. The primary outcomes were the symptom severity scale (SSS) and functional severity scale (FSS) scores of the Boston Carpal Tunnel Questionnaire (BCTQ). The secondary outcomes were electrophysiological studies, including distal motor latency (DML) and sensory nerve conduction velocity (SNCV), cross-sectional area (CSA) of the median nerve (MN), and patient-reported successful clinical response. Assessments were performed before treatment and at one, 3, 6, and 12 months after treatment. RESULTS: A total of 60 patients (30 per group) completed the trial. Compared to the baseline, both groups exhibited improvement in SSS, FSS, SNCV, DML, and CSA at all follow-up time points, with statistical differences for SSS, FSS, and SNCV at 3, 6, and 12 months (P < 0.05), DML at 6 and 12 months (P < 0.05), and CSA at each follow-up time point (P < 0.05). Compared to the short-axis group, the long-axis group exhibited more improvement in SSS and FSS at all follow-up time points, with statistical differences at 3, 6, and 12 months (P < 0.05), and in SNCV and DML at 6 and 12 months (P < 0.05). Although the long-axis patients exhibited more improvement in their wrists' CSAs, the intergroup differences were nonsignificant at all follow-up time points (P > 0.05). Four patients in the short-axis group experienced recurrent symptoms and underwent surgery at 12 months, whereas no recurrence was observed in the long-axis group. LIMITATIONS: A relevant future trial with a longer follow-up period than this one used is still necessary. CONCLUSIONS: Ultrasound-guided TCL needle release via the long-axis approach appears to be more effective than the short-axis approach for treating mild to moderate CTS.

The Tweedledum and Tweedledee of dynamic decisions: Discriminating between diffusion decision and accumulator models.

Theories of dynamic decision-making are typically built on evidence accumulation, which is modeled using racing accumulators or diffusion models that track a shifting balance of support over time. However, these two types of models are only two special cases of a more general evidence accumulation process where options correspond to directions in an accumulation space. Using this generalized evidence accumulation approach as a starting point, I identify four ways to discriminate between absolute-evidence and relative-evidence models. First, an experimenter can look at the information that decision-makers considered to identify whether there is a filtering of near-zero evidence samples, which is characteristic of a relative-evidence decision rule (e.g., diffusion decision model). Second, an experimenter can disentangle different components of drift rates by manipulating the discriminability of the two response options relative to the stimulus to delineate the balance of evidence from the total amount of evidence. Third, a modeler can use machine learning to classify a set of data according to its generative model. Finally, machine learning can also be used to directly estimate the geometric relationships between choice options. I illustrate these different approaches by applying them to data from an orientation-discrimination task, showing converging conclusions across all four methods in favor of accumulator-based representations of evidence during choice. These tools can clearly delineate absolute-evidence and relative-evidence models, and should be useful for comparing many other types of decision theories.

PMCA to demonstrate prions inactivation method efficacy on reusable medical devices: a relevant alternative to animal bioassays.

Validation of prion inactivation processes for medical devices relies on in vivo experimental protocols. However, bioassays are costly, long (one to two years) and ethically disputable. Additionally, results obtained with one prion strain, for example 263K (hamster-adapted strain originating from sheep scrapie), cannot be easily extrapolated to relevant human prion strains, further questioning the utility of bioassays. Over the past two decades, cell-free prion amplification assays have emerged as potential alternatives to bioassays. Rather than measuring prion infectivity, they quantify prion seeding activity, i.e. the capacity to convert the normal prion protein into the disease-associated isoform. The results obtained by an optimized cell-free assay termed miniaturized-bead protein misfolding cyclic amplification (mb-PMCA), with four processes using three different prion strains, 263K and two human prions derived from variant and sporadic Creutzfeldt-Jakob diseases, were compared to published bioassays using the same three strains and processes, when available. Tests performed on reference processes (steam, sodium hydroxide, sodium hypochlorite) and low temperature H2O2 sterilization process (STERRAD NXTM Advanced cycle), showed perfect alignment between mb-PMCA and available bioassays. STERRAD NXTM Advanced cycle was efficacious on all three prion strains. These data confirm that PMCA and in particular mb-PMCA is a relevant alternative to animal bioassays for assessment of prion inactivation processes and the interest of some low temperature H2O2 sterilization cycles.

The network analysis of anxiety, depression and academic burnout symptom relationships throughout early, middle, and late adolescence.

BACKGROUND: Previous research has explored the associations between anxiety, depression, and academic burnout primarily from a variable-level perspective. However, there is limited understanding of which symptoms might play a significant role in anxiety, depression, and academic burnout among adolescents at different stages. METHODS: This study included 7,286 adolescents aged 10 to 18. Questionnaires assessed participants' anxiety, depression, and academic burnout. Network analysis was conducted on the overall sample and segmented by early, middle, and late adolescence to explore relationships between symptoms and variations in symptom expression across these stages, aiming to propose effective interventions targeting anxiety, depression, and academic burnout symptoms in early, middle, and late adolescence. RESULTS: The study found that "feeling that studying is meaningless" emerged as a core symptom in the overall sample. Additionally, "acting or speaking slowly" emerged as a core symptom in early adolescence, while "the thought of dying or hurting" and "feeling bad about yourself, letting your family down" were prominent in middle adolescence, and "easily annoyed or irritable" and "feeling tired" may be prioritized in late adolescence. The varying central symptoms across different adolescent stages suggest the need for targeted interventions. CONCLUSION: These findings underscore the importance of interventions tailored to specific symptoms to meet the unique needs of adolescents at different developmental stages.