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PhyML is a phylogeny software based on the maximum-likelihood principle. Early PhyML versions used a fast algorithm performing nearest neighbor interchanges to improve a reasonable starting tree topology. Since the original publication (Guindon S., Gascuel O. 2003. A simple, fast and accurate algorithm to estimate large phylogenies by maximum likelihood. Syst. Biol. 52:696–704), PhyML has been widely used (>2500 citations in ISI Web of Science) because of its simplicity and a fair compromise between accuracy and speed. In the meantime, research around PhyML has continued, and this article describes the new algorithms and methods implemented in the program. First, we introduce a new algorithm to search the tree space with user-defined intensity using subtree pruning and regrafting topological moves. The parsimony criterion is used here to filter out the least promising topology modifications with respect to the likelihood function. The analysis of a large collection of real nucleotide and amino acid data sets of various sizes demonstrates the good performance of this method. Second, we describe a new test to assess the support of the data for internal branches of a phylogeny. This approach extends the recently proposed approximate likelihood-ratio test and relies on a nonparametric, Shimodaira—Hasegawa—like procedure. A detailed analysis of real alignments sheds light on the links between this new approach and the more classical nonparametric bootstrap method. Overall, our tests show that the last version (3.0) of PhyML is fast, accurate, stable, and ready to use. A Web server and binary files are available from http://www.atgc-montpellier.fr/phyml/.

PhyML is a phylogeny software based on the maximum-likelihood principle. Early PhyML versions used a fast algorithm performing nearest neighbor interchanges to improve a reasonable starting tree topology. Since the original publication (Guindon S., Gascuel O. 2003. A simple, fast and accurate algorithm to estimate large phylogenies by maximum likelihood. Syst. Biol. 52:696–704), PhyML has been widely used (>2500 citations in ISI Web of Science) because of its simplicity and a fair compromise between accuracy and speed. In the meantime, research around PhyML has continued, and this article describes the new algorithms and methods implemented in the program. First, we introduce a new algorithm to search the tree space with user-defined intensity using subtree pruning and regrafting topological moves. The parsimony criterion is used here to filter out the least promising topology modifications with respect to the likelihood function. The analysis of a large collection of real nucleotide and amino acid data sets of various sizes demonstrates the good performance of this method. Second, we describe a new test to assess the support of the data for internal branches of a phylogeny. This approach extends the recently proposed approximate likelihood-ratio test and relies on a nonparametric, Shimodaira–Hasegawa–like procedure. A detailed analysis of real alignments sheds light on the links between this new approach and the more classical nonparametric bootstrap method. Overall, our tests show that the last version (3.0) of PhyML is fast, accurate, stable, and ready to use. A Web server and binary files are available from http://www.atgc-montpellier.fr/phyml/.

Background: Lattice Radiation Therapy (LRT), a spatially fractionated stereotactic radiotherapy (SBRT) technique, has shown promising results in the palliative treatment of large tumors. The focus of our first analysis of 56 lesions ≥7 cm was on the extent of shrinkage following palliative LRT (mean 50%) and assessment of its effect duration (: mean 6 months). Herewith we present an updated analysis of our single-center LRT cohort, with a focus on LRT outcome across diagnoses and applied LRT regimens. Methods: We assessed the clinical outcome following LRT in 66 patients treated for 81 lesions between 01.2022 and 05.2025. LRT protocols included simultaneous integrated boost (sib-) LRT in 49 lesions (5 × 4–5 Gy to the entire mass with sib of 9–13 Gy to lattice vertices). Alternatively mainly in pre-irradiated and/or very large lesions—a single-fraction stereotactic LRT (SBRT-LRT) of 1 × 20 Gy to vertices only was delivered to 26 lesions. In six cases with modest response to single fraction SBRT-LRT, the sib-LRT schedule was added 4–8 weeks later. Results: The median age was 68 years (18–93). Main tumor locations were abdomino-pelvic (n = 34) and thoracic (n = 17). Histopathological diagnoses included carcinoma (n = 34), sarcoma (n = 31), and melanoma (n = 16). 31% of all lesions have been previously irradiated. 73% of cases underwent concurrent or peri-LRT systemic therapy. The mean/median overall survival (OS) time of the cohort was 7.6/4.6 months (0.4–40.2), 11.9/5.8 months in 16/66 alive, and 6.4/4.3 months in deceased patients, respectively. 82% of symptomatic patients reported immediate subjective improvement (PROM), with a lifelong response duration in most cases. Progressive disease (PD: >10% increase in initial volume) was found in 9%, stable disease (SD +/−10% of initial volume) in 19% of scanned lesions, and shrinkage (>10% reduction in initial volume) in 75%, with a mean/median tumor volume reduction of 51/60%. The extent of shrinkage was found to be 11–30%/31–60%/61–100% in 38/24/38% of lesions. Response rates (PD, SD, shrinkage) following the two applied LRT regimens, as well as those related to sarcoma and carcinoma diagnoses, were found to be comparable. Treatment tolerance was excellent (G0-1). Conclusions: Palliative LRT provides rapid subjective relief in ~80% of symptomatic patients. Radiologic shrinkage was stated in 75% of FU-scanned lesions, with a lifelong effect duration in most patients. LRT was found effective across histologies, with a similar extent of shrinkage in carcinoma and sarcoma following 1F SBRT- and 5F sib-LRT regimens, respectively.

The problem of testing the equality of coefficients of variation of independent normal populations is considered. For comparing two coefficients, we consider the signed-likelihood ratio test (SLRT) and propose a modified version of the SLRT, and a generalized test. Monte Carlo studies on the type I error rates of the tests indicate that the modified SLRT and the generalized test work satisfactorily even for very small samples, and they are comparable in terms of power. Generalized confidence intervals for the ratio of (or difference between) two coefficients of variation are also developed. A modified LRT for testing the equality of several coefficients of variation is also proposed and compared with an asymptotic test and a simulation-based small sample test. The proposed modified LRTs seem to be very satisfactory even for samples of size three. The methods are illustrated using two examples.

Despite the relevant role of models of nucleotide substitution in phylogenetics, choosing among different models remains a problem. Several statistical methods for selecting the model that best fits the data at hand have been proposed, but their absolute and relative performance has not yet been characterized. In this study, we compare under various conditions the performance of different hierarchical and dynamic likelihood ratio tests, and of Akaike and Bayesian information methods, for selecting best-fit models of nucleotide substitution. We specifically examine the role of the topology used to estimate the likelihood of the different models and the importance of the order in which hypotheses are tested. We do this by simulating DNA sequences under a known model of nucleotide substitution and recording how often this true model is recovered by the different methods. Our results suggest that model selection is reasonably accurate and indicate that some likelihood ratio test methods perform overall better than the Akaike or Bayesian information criteria. The tree used to estimate the likelihood scores does not influence model selection unless it is a randomly chosen tree. The order in which hypotheses are tested, and the complexity of the initial model in the sequence of tests, influence model selection in some cases. Model fitting in phylogenetics has been suggested for many years, yet many authors still arbitrarily choose their models, often using the default models implemented in standard computer programs for phylogenetic estimation. We show here that a best-fit model can be readily identified. Consequently, given the relevance of models, model fitting should be routine in any phylogenetic analysis that uses models of evolution.

Introduction Vocal cord dysfunction (VCD) is a complex disorder characterized by episodic adduction of the vocal folds during inspiration and expiration, which can lead to dyspnea, wheezing, cough, and acute‐onset respiratory distress. Currently, there is a lack of standardized criteria among treating physicians across multiple disciplines, including otolaryngologists, pulmonologists, allergists, and speech and language pathologists, for diagnosis and treatment of VCD, although laryngeal‐respiratory retraining therapy (LRT) has emerged as the preferred treatment modality. Objective In the present study, we examined the efficacy of LRT in patients presenting with a clinical diagnosis of VCD in the presence and absence of laryngeal adduction on laryngoscopy. Results Overall, 74.1% of the cohort showed a response to LRT, of which 62.1% were partial and 12.1% were significant responses. When comparing between patients with and without laryngeal adduction on laryngoscopy, there were no significant differences in the number of sessions of LRT undertaken, mean time to response, and overall response rate between the groups. Conclusion Our findings suggest that LRT should be utilized for all patients presenting with symptoms of VCD, even in the absence of laryngeal adduction on laryngoscopy. In this retrospective study, we found that abnormal or normal laryngoscopy findings did not predict patient‐reported outcomes in response to speech therapy among a cohort of patients with vocal cord dysfunction (VCD). This finding is significant because it provides further evidence for the utility of speech therapy even in patients with only a clinical presumption of VCD with objectively normal laryngoscopy findings. To date, the literature regarding outcomes for VCD is still lacking, and thus we believe that this manuscript would be interesting and relevant for your audience.

Background: The clinical outcome of inoperable sarcoma patients treated with LATTICE (LRT) is limited and therefore the objective of our study was to report treatment response, overall survival (OS), local-recurrence free survival (LRFS) and toxicity. Methods: This retrospective observational study includes 15 histologically proven inoperable non-extremity sarcoma patients with no treatment options or no response to systemic therapy, treated at our institution between 2020 and 2024. The patients were treated with a combination of LRT and normo- or hypo-fractionated external beam radiotherapy. Treatment response was evaluated by RECIST1.1 criteria, toxicity by CTCAE 5.0 and OS and LRFS by Kaplan–Meier curves. Results: The median follow-up (F-UP) since the beginning of the treatment was 10 months (range 4–32). Nine patients were male and six female. Their mean age was 60 years. The median gross tumor volume (GTV) was 1058 cm3 (range 142–6103 cm3). The median number of spheres was 9 (4–30). All patients with symptoms reported symptoms’ relief. Based on RECIST1.1 criteria, 10 patients (67%) had stable local disease at 1–2 months F-UP on computed tomography (CT). Surgical resection was feasible in five patients. Three of them are alive without disease and two died due to metastatic progression. From 10 (67%) non operated patients, 5 patients died (50%) due to disease. The remaining five patients (50%) are alive, three with stable disease at 21, 22, and 32 months of F-UP and two with disease progression who are currently receiving palliative chemotherapy treatment. Reported G2 toxicity was as follows: gastrointestinal (2), asthenia (1). Two patients had G3 toxicity: esophagitis (1) and inguinal dermatitis (1). No acute or chronic G4–G5 toxicity was observed. Conclusions: LRT is a feasible and well-tolerated radiation technique for inoperable bulky soft-tissue sarcomas. Further studies are needed to establish protocols to determine which patients could benefit from palliative or preoperative treatment.

We simultaneously collected 85 pairs of 24-h PM1.0 and PM 2.5 samples from a new urban area in Hanoi, Vietnam, and analyzed their chemical compositions with particle-induced X-ray emission (PIXE) and ion chromatography (IC) to obtain input data for source apportionment via positive matrix factorization (PMF). Sulfate, ammonium, and black carbon (BC) composed the majority of the mass in both size fractions, and the PMF models clearly differentiated the contribution of long-range transport (LRT) aerosols, which accounted for more than two-thirds of the measured PM-bound sulfate and ammonium concentrations, from those of the six in situ sources, viz., resuspended road dust, primary vehicular emissions, coal fly ash, biomass burning emissions, construction dust, and sea salt. Whereas LRT aerosols, coal fly ash, and primary particulate vehicular emissions mainly occurred in the PM 1.0 , resuspended road dust and biomass-burning fly ash tended to appear in the PM 1.0–2.5 ; hence, we can characterize the anthropogenic emissions in this area by examining the profile of the PM 1.0 rather than the PM 2.5 . Additionally, air masses with inland trajectories originating in northern China and countries northwest and southwest of Vietnam contained more ammonium, sulfate, and BC than those that passed over the East Sea. Finally, the LRT aerosols exhibited high acidity in the PM 1.0 but neutrality in the PM 2.5 .

Background: Patients bearing large-volume, bulky primary or relapsed tumors, are usually referred to palliative low-dose radiotherapy with very poor results. Lattice Radiation Therapy (LRT) is able to produce a high number of high-dose foci or vortexes (multiple SBRT treatments), separated by low-dose zones (valleys). Treatment planning on vortex placing, valley definition, and dose administered depends on individual decisions of the treating team. The aim of our study is to assess for the first time the possibility of a dense fractionated LRT within the target volume. Methods: A total of 22 treatments in 20 patients were performed in the frame of a prospective observational study of fractionated LRT ongoing in our institution. According to our aim of achieving dense LRT, no GTV contraction was considered to create the LRTV (GTV is equal to LRTV). The vortexes were segmented as 1 cm diameter at a 1.5 cm vortex-to-vortex distance. Dose prescription to the vortexes per fraction was 12 Gy. Results: The vortex/LRTV ratio was 7.38 ± 2.13% (3.4–10.40%, median 7.60%). Mean dose to the vortex volume was 11.90 ± 0.09 Gy (11.70–12.10 Gy, median 11.90 Gy). Mean dose administered to the valley volume was 8.29 ± 0.70 (7.05–9.51 Gy, median 8.29 Gy). Valley/vortex (peak) dose ratio (VPDR) was 69.40 ± 6.02% (59.00–79.80%, median 69.70%). The mean peripheral tumor dose was 5.11 ± 0.8710 Gy (3.16–6.78 Gy, median 5.18 Gy). Conclusions: Our dense LRT schedule fulfilled most of the recommended guidelines for LRT, increasing the high dose points without risking the dose to the surrounding tissues. Further analysis of feasibility and safety are needed to secure the clinical relevance of our proposed protocol.

The interquartile range is a statistical measure well suited to describe the variability of the data at hand, both at the population level and for sample data. The interquartile range is particularly useful when the distribution of the data is asymmetric or irregularly shaped. Here, the use of the interquartile range is investigated when the main aim is to compare the variability of two distributions using two independent random samples, without the need to make any distributional assumptions. Several techniques are compared through numerical studies and real data examples, with a particular attention given to the use of sample quantiles based on the Harrel-Davis estimator or the quantile regression.