Clinical efficacy of olfactory training using aromatic traditional Chinese medicine in managing olfactory dysfunction induced by SARS-CoV-2.

OBJECTIVE: The aim of this study is to assess the clinical efficacy of olfactory training using aromatic traditional Chinese medicine (TCM) for addressing severe acute respiratory syndrome-coronavirus-2 (SARS-CoV-2)-induced olfactory dysfunction, while also exploring the factors that influence the observed efficacy. METHODS: 172 outpatients with SARS-CoV-2-related olfactory dysfunction were randomized into two groups. The experimental group received olfactory training with TCM aromatics (ginger, Pericarpium Citri Reticulatae, Santali Albi Lignum, Styrax), while the control group used non-TCM aromatics (phenyl ethanol-rose, menthol-mint, citronellal-lemon, eugenol-clove) for 24 weeks. Olfactory function was assessed using the Sniffin' Sticks test and TDI (threshold-discrimination-identification) scores at baseline, 1, 3, and 6 months post-treatment. RESULTS: Response rates at 1, 3, and 6 months post-treatment were 3.66%, 25.61%, and 43.90% in the experimental group, and 4.94%, 23.46%, and 43.21% in the control group. The TDI scores of the experimental group and the control group were statistically different before and after treatment. At 3 and 6 months post-treatment, TDI scores increased significantly, with enhanced odor discrimination and identification capabilities in both groups compared to pre-treatment, while the odor detection threshold was not improved compared with that before treatment. At the 3- and 6-month follow-ups, experimental group showed significantly higher self-rated sleep and anxiety scores than controls, indicating notable improvement in both after treatment. CONCLUSION: Olfactory training with aromatic TCM offers an effective treatment for SARS-CoV-2-induced olfactory dysfunction, improving odor discrimination, identification without significant differences compared to conventional aromatics, besides, it may also improve anxiety and sleep quality.

[Clinical features and surgical treatment of right cardiac system tumors].

A total of 25 patients with right cardiac system tumors in the Department of Cardiac Surgery, Beijing Anzhen Hospital from January 2012 to October 2022 were retrospectively included in the study. The preoperative data, and information of surgical treatment and perioperative management on these patients were analyzed and summarized. One patient developed pulmonary embolism and died before surgery, and the other 24 patients (16 males and 8 females) received surgical treatment, with an average age of (44.7±10.2) years (24-74 years). Nine patients were diagnosed with malignant tumors. Among the 24 patients who received surgical treatment, two patients died during the perioperative period, in-situ tumor recurrence was seen in three patients within about 1 year after surgery (two patients died without surgery, and one patient died 3 months after surgery), two patients had distant metastasis, and 17 patients had a good prognosis. Right cardiac system tumors are rare, with a high malignant rate, and the clinical manifestations vary greatly. Active surgical intervention is found to be effective, and the prognosis is closely related to the pathological type and extent of tumor invasion.

Prognostic Value of Acute Gastrointestinal Injury Combined with Disease Severity Scores in Critically Ill Patients.

Background: Critically ill patients are at high risk of multiple organ failure syndrome (MODS) and gastrointestinal (GI) injury and dysfunction, which are associated with increased mortality rates. The acute gastrointestinal injury (AGI) scale has shown promise in assessing GI dysfunction. However, the combined utility of AGI with established disease severity scores remains unclear. This study aimed to investigate the performance of AGI in conjunction with modified nutritional risk in critically ill (mNUTRIC), sequential organ failure assessment (SOFA), and acute physiology and chronic health evaluation II (APACHE II) scores for predicting mortality in critically ill patients. Materials and methods: A retrospective cross-sectional study was conducted in the intensive care unit (ICU) from May 2021 to December 2021. Demographic and clinical data were collected, including AGI grade, mNUTRIC score, SOFA score, APACHE II score, and mortality. Results: Among 93 critically ill patients, AGI was observed in 47.3% of cases, and the in-hospital mortality rate was 30.1%. The area under the curve (AUC) for AGI in predicting in-hospital mortality was 0.67 [95% confidence interval (CI), 0.56, 0.79; p = 0.008], similar to the AUCs of SOFA, APACHE II, and mNUTRIC scores. The combination of AGI with mNUTRIC, APACHE II, or SOFA scores improved the predictive performance compared with AGI alone. Conclusion: The AGI grade, in conjunction with disease severity scores, such as mNUTRIC, SOFA, and APACHE II scores, shows promise in predicting mortality in critically ill patients. Integrating AGI into evaluating critically ill patients can enhance prognostic accuracy. How to cite this article: Hai PD, Tot NH, Thao LT, Khoa Q, Thien DH. Prognostic Value of Acute Gastrointestinal Injury Combined with Disease Severity Scores in Critically Ill Patients. Indian J Crit Care Med 2024;28(6):575-580.

Coevolution of Patch Selection in Stochastic Environments.

AbstractSpecies interact in landscapes where environmental conditions vary in time and space. This variability impacts how species select habitat patches. Under equilibrium conditions, evolution of this patch selection can result in ideal free distributions where per capita growth rates are zero in occupied patches and negative in unoccupied patches. These ideal free distributions, however, do not explain why species occupy sink patches, why competitors have overlapping spatial ranges, or why predators avoid highly productive patches. To understand these patterns, we solve for coevolutionarily stable strategies (coESSs) of patch selection for multispecies stochastic Lotka-Volterra models accounting for spatial and temporal heterogeneity. In occupied patches at the coESS, we show that the differences between the local contributions to the mean and the variance of the long-term population growth rate are equalized. Applying this characterization to models of antagonistic interactions reveals that environmental stochasticity can partially exorcize the ghost of competition past, select for new forms of enemy-free and victimless space, and generate hydra effects over evolutionary timescales. Viewing our results through the economic lens of modern portfolio theory highlights why the coESS for patch selection is often a bet-hedging strategy coupling stochastic sink populations. Our results highlight how environmental stochasticity can reverse or amplify evolutionary outcomes as a result of species interactions or spatial heterogeneity.

Electrostatic and Covalent Assemblies of Anionic Hydrogel-Coated Gold Nanoshells for Detection of Dry Eye Biomarkers in Human Tears.

Although dry eye is highly prevalent, many challenges exist in diagnosing the symptom and related diseases. For this reason, anionic hydrogel-coated gold nanoshells (AuNSs) were used in the development of a label-free biosensor for detection of high isoelectric point tear biomarkers associated with dry eye. A custom, aldehyde-functionalized oligo(ethylene glycol)acrylate (Al-OEGA) was included in the hydrogel coating to enhance protein recognition through the formation of dynamic covalent (DC) imine bonds with solvent-accessible lysine residues present on the surface of select tear proteins. Our results demonstrated that hydrogel-coated AuNSs, composed of monomers that form ionic and DC bonds with select tear proteins, greatly enhance protein recognition due to changes in the maximum localized surface plasmon resonance wavelength exhibited by AuNSs in noncompetitive and competitive environments. Validation of the developed biosensor in commercially available pooled human tears revealed the potential for clinical translation to establish a method for dry eye diagnosis.

A general theory of coexistence and extinction for stochastic ecological communities.

We analyze a general theory for coexistence and extinction of ecological communities that are influenced by stochastic temporal environmental fluctuations. The results apply to discrete time (stochastic difference equations), continuous time (stochastic differential equations), compact and non-compact state spaces and degenerate or non-degenerate noise. In addition, we can also include in the dynamics auxiliary variables that model environmental fluctuations, population structure, eco-environmental feedbacks or other internal or external factors. We are able to significantly generalize the recent discrete time results by Benaim and Schreiber (J Math Biol 79:393-431, 2019) to non-compact state spaces, and we provide stronger persistence and extinction results. The continuous time results by Hening and Nguyen (Ann Appl Probab 28(3):1893-1942, 2018a) are strengthened to include degenerate noise and auxiliary variables. Using the general theory, we work out several examples. In discrete time, we classify the dynamics when there are one or two species, and look at the Ricker model, Log-normally distributed offspring models, lottery models, discrete Lotka-Volterra models as well as models of perennial and annual organisms. For the continuous time setting we explore models with a resource variable, stochastic replicator models, and three dimensional Lotka-Volterra models.

Endoscopic sinus surgery improves Eustachian tube function in patients with chronic rhinosinusitis: a multicenter prospective study.

BACKGROUND: Patients with chronic rhinosinusitis (CRS) often have Eustachian tube dysfunction (ETD) symptoms. This study aimed to prospectively investigate the effect of endoscopic sinus surgery (ESS) on improvement of Eustachian tube function in CRS patients with ETD from a Chinese population and determine factors associated with improvement. METHODS: A prospective study was performed in CRS patients with ETD who underwent ESS from 3 tertiary medical centers in south China. The Eustachian tube Dysfunction Questionnaire 7 (ETDQ-7), Sinonasal Outcome Test 22 (SNOT-22), tympanograms, endoscopic findings and Valsalva maneuver were recorded and analyzed preoperatively and postoperatively at 8-12 weeks. RESULTS: A total of 70 CRS patients with ETD were included in this study. The ETDQ-7 score and the ability of positive Valsalva maneuver in CRS patients were significantly improved postoperatively at 8-12 weeks. The number of patients with type A tympanogram was increased postoperatively. Reduced Eustachian tube mucosal inflammation was also observed postoperatively. In addition, ESS appeared to reverse slight tympanic membrane atelectasis after 8-12 weeks. Moreover, improvement in tympanogram was presented in more than half of CRS patients with concomitant otitis media with effusion postoperatively at 8-12 weeks. Univariate and multivariate analysis revealed failure of normalization of ETDQ-7 postoperatively was associated with concomitant allergic rhinitis and higher preoperative SNOT-22 score. CONCLUSIONS: This study confirms Eustachian tube function is often improved after ESS in CRS patients with ETD. Concomitant allergic rhinitis and higher preoperative SNOT-22 score are associated with failure of normalization of ETD symptoms.

Molecular identification and characterisation of a novel chicken leukocyte immunoglobulin-like receptor A5.

1. Leukocyte immunoglobulin-like receptor A5 (LILRA5) is a key molecule that regulates the immune system. However, the LILRA5 gene has not been characterised in avian species, including chickens. The present study aimed to identify and functionally characterise LILRA5 identified from two genetically disparate chicken lines, viz., Marek's disease (MD)-resistant (R) line 6.3 and MD-susceptible (S) line 7.2. 2. Multiple sequence alignment and phylogenetic analyses confirmed that the identity and similarity homologies of amino acids of LILRA5 in chicken lines 6.3 and 7.2 ranged between 93% and 93.7%, whereas those between chicken and mammals ranged between 20.9% and 43.7% and 21.1% to 43.9%, respectively. The newly cloned LILRA5 from chicken lines 6.3 and 7.2 revealed high conservation and a close relationship with other known mammalian LILRA5 proteins. 3. The results indicated that LILRA5 from chicken lines 6.3 and 7.2 was associated with phosphorylation of Src kinases and protein tyrosine phosphatase non-receptor type 11 (SHP2), which play a regulatory role in immune functions. Moreover, the results demonstrated that LILRA5 in these lines was associated with the activation of major histocompatibility complex (MHC) class I and ß2-microglobulin and induced the expression of the transporter associated with antigen processing. In addition, LILRA5 in both chicken lines activated and induced Janus kinase (JAK)-signal transducer and the activator of transcription (STAT), nuclear factor kappa B (NF-κB), phosphoinositide-3-kinase (PI3K)/protein kinase B (AKT) and the extracellular signal-regulated kinase (ERK)1/2 signalling pathways; toll-like receptors; and Th1-, Th2-, and Th17- cytokines. 4. The data suggested that LILRA5 has innate immune receptors essential for macrophage immune response and provide novel insights into the regulation of immunity and immunopathology.

The competitive exclusion principle in stochastic environments.

In its simplest form, the competitive exclusion principle states that a number of species competing for a smaller number of resources cannot coexist. However, it has been observed empirically that in some settings it is possible to have coexistence. One example is Hutchinson's 'paradox of the plankton'. This is an instance where a large number of phytoplankton species coexist while competing for a very limited number of resources. Both experimental and theoretical studies have shown that temporal fluctuations of the environment can facilitate coexistence for competing species. Hutchinson conjectured that one can get coexistence because nonequilibrium conditions would make it possible for different species to be favored by the environment at different times. In this paper we show in various settings how a variable (stochastic) environment enables a set of competing species limited by a smaller number of resources or other density dependent factors to coexist. If the environmental fluctuations are modeled by white noise, and the per-capita growth rates of the competitors depend linearly on the resources, we prove that there is competitive exclusion. However, if either the dependence between the growth rates and the resources is not linear or the white noise term is nonlinear we show that coexistence on fewer resources than species is possible. Even more surprisingly, if the temporal environmental variation comes from switching the environment at random times between a finite number of possible states, it is possible for all species to coexist even if the growth rates depend linearly on the resources. We show in an example (a variant of which first appeared in Benaim and Lobry '16) that, contrary to Hutchinson's explanation, one can switch between two environments in which the same species is favored and still get coexistence.

[Impact of left ventricle remodeling on perioperative risk and short-term prognosis in patients with heart failure and reduced ejection fraction undergoing coronary artery bypass grafting].

Objective: To explore the impact of left ventricle remodeling on perioperative risk and short-term survival in patients with heart failure and reduced ejection fraction (HFrEF) undergoing coronary artery bypass grafting (CABG). Methods: A total of 78 coronary artery disease (CAD) patients (54 males, 24 females) with symptoms and signs of heart failure and a left ventricular ejection fraction (LVEF)<40% were consecutively enrolled from January 2014 to December 2018 in Beijing Anzhen Hospital. The average age was (59±8) years old. Transthoracic echocardiography was performed to measure LVEF and left ventricle end-systolic volume index (LVESVI) during hospitalization, and the average LVESVI was (92±18) ml/m(2). According to the mean value of LVESVI, the patients were divided into 2 groups: mild left ventricle remodeling group (group M, n=46, LVESVI<92 ml/m(2)) and severe left ventricle remodeling group (group S, n=32, LVESVI≥92 ml/m(2)). The follow-up period was (30±12) months. Operative mortality, perioperative complications and long-term survival were compared between the two groups. Results: Perioperative mortality was 5.1% (4/78), which was significantly higher in group S than that of group M (9.4% vs 2.2%, P=0.03). The proportion of patients with intra-aortic balloon pump (IABP) was higher in group S than that of group M during the perioperative period (62.5% vs 36.9%, P<0.01). Compared with patients in group M, those with severe left ventricle remodeling were more susceptible to atrial fibrillation after surgery (25.0% vs 6.5%, P=0.02). The mean follow-up time was (30±12) months. There was no difference in major adverse cardiac event (MACE)-free survival in 12 month, 24 month and 36 month between the two groups (100% vs 100%, 87.9% vs 92.1%, 80.3% vs 78.3%, P=0.68). Conclusion: Left ventricular remodeling increases the perioperative mortality and complications of patients with ischemic HFrEF undergoing CABG, but it has no impact on short-term survival.

[Clinical analysis of 12 cases of acute myeloid leukemia complicated with synchronous primary solid tumor].

Objective: To explore the clinical characteristics of acute myeloid leukemia (AML) complicated with simultaneous multiple primary cancer (SMPC). Methods: The data of 12 AML patients with SMPC hospitalized in the Affiliated Cancer Hospital of Zhengzhou University, the First Affiliated Hospital of Nanyang Medical College, the Xinhua District Hospital of Pingdingshan City and the First People's Hospital of Pingdingshan City from March 2014 to July 2019 were analyzed retrospectively, and their clinical features, treatment and prognosis were summarized. Results: Among the 12 patients, there were 6 males and 6 females, with a median age of 58 years (39-70 years). AML classification: according to French-American-British (FAB) classification, the 12 AML patients were classified as M0 1, M1 1, M2a 5, M2b 1, M3 2, M5 2; according to National Comprehensive Cancer Network (NCCN) prognosis stratified, low risk group 1 case, medium risk group 4 cases, high risk group 7 cases; classification of solid tumors: 3 cases of lung cancer, 1 case of breast cancer, 2 cases of gastric cancer, 3 cases of esophageal cancer, 1 case of rectal neuroendocrine tumor, 1 case of invasive hydatidiform mole and 1 case of sigmoid colon cancer. The median time interval for the diagnosis of two primary malignant tumors was 4 (from 2.6 to 5.6) months. Results of gene mutation detection: AML prognostic gene detection results: a total of 12 kinds of gene abnormalities including ASXL1, JAK2, TET2, U2AF1, ABCB1, FLT3-ITD, RUNX1, SETBPIT, TET2 (single nucleotide polymorphism, SNP), p53, IKZF1 and IDH2 were detected, and solid tumor related genes were detected: a total of 4 kinds of gene abnormalities including Her-2, EGFR, K-RAS and MSI were detected. Survival: among the 12 patients, 1 case was lost during follow-up, 2 cases were still in treatment, 3 cases ended treatment and the condition was stable, 6 cases died. The median overall survival of 12 patients was 12.5 (from 3.8 to 48.0) months. Conclusions: It is not clear whether there is a certain correlation between the simultaneous occurrence of AML and solid tumors. Patients with AML and synchronous solid tumors are not unusual. Both tumors should be treated aggressively at the same time.

Asymptotic harvesting of populations in random environments.

We consider the harvesting of a population in a stochastic environment whose dynamics in the absence of harvesting is described by a one dimensional diffusion. Using ergodic optimal control, we find the optimal harvesting strategy which maximizes the asymptotic yield of harvested individuals. To our knowledge, ergodic optimal control has not been used before to study harvesting strategies. However, it is a natural framework because the optimal harvesting strategy will never be such that the population is harvested to extinction-instead the harvested population converges to a unique invariant probability measure. When the yield function is the identity, we show that the optimal strategy has a bang-bang property: there exists a threshold [Formula: see text] such that whenever the population is under the threshold the harvesting rate must be zero, whereas when the population is above the threshold the harvesting rate must be at the upper limit. We provide upper and lower bounds on the maximal asymptotic yield, and explore via numerical simulations how the harvesting threshold and the maximal asymptotic yield change with the growth rate, maximal harvesting rate, or the competition rate. We also show that, if the yield function is [Formula: see text] and strictly concave, then the optimal harvesting strategy is continuous, whereas when the yield function is convex the optimal strategy is of bang-bang type. This shows that one cannot always expect bang-bang type optimal controls.

[Short-term outcomes of sequential radial artery grafting in patients with coronary artery disease].

Objective: To explore the short-term outcomes of patients with coronary artery disease (CAD) who underwent coronary artery bypass graft (CABG) with sequential radial artery graft. Methods: Clinical data of patients with CAD who underwent CABG with sequential radial artery graft from August to December 2018 in Beijing Anzhen Hospital was retrospectively analyzed. Computer tomography angiography was employed to evaluate the patency of grafts and the incidence of adverse cardiovascular events was followed up 3 months after surgery. Results: A total of thirty patients were included, with an average age of (60.2±7.3) years old, among whom 83.3% were male, and 93.3% had three-vessel disease detected by coronary angiography. All patients had left internal mammary artery (LIMA) anastomosed to the left anterior descending (LAD) and sequential radial artery graft. Among sequential radial artery grafts, the most frequent anastomosis of sequential radial artery graft was aortic artery (AO)-first diagonal branch (D1)-first obtuse marginal branch (OM1) (13 patients, 43.3%), followed by AO-OM1-second obtuse marginal branch (OM2) (9 patients, 30.0%), and 18 patients also underwent saphenous vein graft. None of 30 patients experienced adverse cardiovascular events during postoperative period in hospital. Three-months follow-up outcomes showed that LIMA-LAD in 1 patient (3.3%) occluded, 3 patients had occluded anastomosis of sequential radial artery graft, 1 patient (3.3%) had heart failure, and 1 patient (3.3%) had recurrent angina. Conclusion: The radial artery could be used as the second arterial graft for CAD patients undergoing CABG with a sequential anastomosis technique, and these patients need regular anti-arterial spasm drug treatment after CABG.

Masking by vaccines in pediatric drug safety signal detection in the EudraVigilance database.

PURPOSE: Postmarketing drug safety surveillance relies upon measures of disproportionate reporting in spontaneous reporting systems. It has been hypothesized that products or events reported frequently may "mask" signals. METHODS: We analyzed the masking effect of vaccines in pediatrics in the EudraVigilance database by conducting disproportionality analysis in the full database (containing vaccine exposures) and in a restricted set (excluding vaccine exposures). We measured performance of the reporting odds ratio (ROR) in both data sets using a pediatric-specific drug reference set and in the absence of a reference set. We assessed masking effects across age groups and conducted a classification tree (CART) analysis. RESULTS: Removal of vaccines decreased the ROR values both in negative and positive controls. Exceptions were drug-event combinations including outcomes frequent in vaccine reports. When restricted to positive control associations, removal of vaccine-related events resulted in increased ROR values for events commonly reported following vaccination. For events rarely associated with vaccination, ROR values decreased for all age groups, especially infants. Analysis in the absence of a reference set showed decrease in ROR following vaccine removal and CART revealed that change in ROR with vaccine removal depended upon age and proportion of reports including a vaccine. CONCLUSIONS: Removal of vaccines for signal detection in a pediatric population has an impact on ROR, dependent upon the reporting frequency of the event of interest in combination with vaccines. We recommend stratification by age and removal of vaccine exposures if the investigated adverse drug reactions include those typically reported in association with vaccines for the age strata.

Persistence in Stochastic Lotka-Volterra Food Chains with Intraspecific Competition.

This paper is devoted to the analysis of a simple Lotka-Volterra food chain evolving in a stochastic environment. It can be seen as the companion paper of Hening and Nguyen (J Math Biol 76:697-754, 2018b) where we have characterized the persistence and extinction of such a food chain under the assumption that there is no intraspecific competition among predators. In the current paper, we focus on the case when all the species experience intracompetition. The food chain we analyze consists of one prey and [Formula: see text] predators. The jth predator eats the [Formula: see text]st species and is eaten by the [Formula: see text]st predator; this way each species only interacts with at most two other species-the ones that are immediately above or below it in the trophic chain. We show that one can classify, based on the invasion rates of the predators (which we can determine from the interaction coefficients of the system via an algorithm), which species go extinct and which converge to their unique invariant probability measure. We obtain stronger results than in the case with no intraspecific competition because in this setting we can make use of the general results of Hening and Nguyen (Ann Appl Probab 28:1893-1942, 2018a). Unlike most of the results available in the literature, we provide an in-depth analysis for both non-degenerate and degenerate noise. We exhibit our general results by analyzing trophic cascades in a plant-herbivore-predator system and providing persistence/extinction criteria for food chains of length [Formula: see text].

Stochastic Lotka-Volterra food chains.

We study the persistence and extinction of species in a simple food chain that is modelled by a Lotka-Volterra system with environmental stochasticity. There exist sharp results for deterministic Lotka-Volterra systems in the literature but few for their stochastic counterparts. The food chain we analyze consists of one prey and [Formula: see text] predators. The jth predator eats the [Formula: see text]th species and is eaten by the [Formula: see text]th predator; this way each species only interacts with at most two other species-the ones that are immediately above or below it in the trophic chain. We show that one can classify, based on an explicit quantity depending on the interaction coefficients of the system, which species go extinct and which converge to their unique invariant probability measure. Our work can be seen as a natural extension of the deterministic results of Gard and Hallam '79 to a stochastic setting. As one consequence we show that environmental stochasticity makes species more likely to go extinct. However, if the environmental fluctuations are small, persistence in the deterministic setting is preserved in the stochastic system. Our analysis also shows that the addition of a new apex predator makes, as expected, the different species more prone to extinction. Another novelty of our analysis is the fact that we can describe the behavior of the system when the noise is degenerate. This is relevant because of the possibility of strong correlations between the effects of the environment on the different species.

Stochastic population growth in spatially heterogeneous environments: the density-dependent case.

This work is devoted to studying the dynamics of a structured population that is subject to the combined effects of environmental stochasticity, competition for resources, spatio-temporal heterogeneity and dispersal. The population is spread throughout n patches whose population abundances are modeled as the solutions of a system of nonlinear stochastic differential equations living on [Formula: see text]. We prove that r, the stochastic growth rate of the total population in the absence of competition, determines the long-term behaviour of the population. The parameter r can be expressed as the Lyapunov exponent of an associated linearized system of stochastic differential equations. Detailed analysis shows that if [Formula: see text], the population abundances converge polynomially fast to a unique invariant probability measure on [Formula: see text], while when [Formula: see text], the population abundances of the patches converge almost surely to 0 exponentially fast. This generalizes and extends the results of Evans et al. (J Math Biol 66(3):423-476, 2013) and proves one of their conjectures. Compared to recent developments, our model incorporates very general density-dependent growth rates and competition terms. Furthermore, we prove that persistence is robust to small, possibly density dependent, perturbations of the growth rates, dispersal matrix and covariance matrix of the environmental noise. We also show that the stochastic growth rate depends continuously on the coefficients. Our work allows the environmental noise driving our system to be degenerate. This is relevant from a biological point of view since, for example, the environments of the different patches can be perfectly correlated. We show how one can adapt the nondegenerate results to the degenerate setting. As an example we fully analyze the two-patch case, [Formula: see text], and show that the stochastic growth rate is a decreasing function of the dispersion rate. In particular, coupling two sink patches can never yield persistence, in contrast to the results from the non-degenerate setting treated by Evans et al. which show that sometimes coupling by dispersal can make the system persistent.

ClonEvol: clonal ordering and visualization in cancer sequencing.

BACKGROUND: Reconstruction of clonal evolution is critical for understanding tumor progression and implementing personalized therapies. This is often done by clustering somatic variants based on their cellular prevalence estimated via bulk tumor sequencing of multiple samples. The clusters, consisting of the clonal marker variants, are then ordered based on their estimated cellular prevalence to reconstruct clonal evolution trees, a process referred to as 'clonal ordering'. However, cellular prevalence estimate is confounded by statistical variability and errors in sequencing/data analysis, and therefore inhibits accurate reconstruction of the clonal evolution. This problem is further complicated by intra- and inter-tumor heterogeneity. Furthermore, the field lacks a comprehensive visualization tool to facilitate the interpretation of complex clonal relationships. To address these challenges we developed ClonEvol, a unified software tool for clonal ordering, visualization, and interpretation. MATERIALS AND METHODS: ClonEvol uses a bootstrap resampling technique to estimate the cellular fraction of the clones and probabilistically models the clonal ordering constraints to account for statistical variability. The bootstrapping allows identification of the sample founding- and sub-clones, thus enabling interpretation of clonal seeding. ClonEvol automates the generation of multiple widely used visualizations for reconstructing and interpreting clonal evolution. RESULTS: ClonEvol outperformed three of the state of the art tools (LICHeE, Canopy and PhyloWGS) for clonal evolution inference, showing more robust error tolerance and producing more accurate trees in a simulation. Building upon multiple recent publications that utilized ClonEvol to study metastasis and drug resistance in solid cancers, here we show that ClonEvol rediscovered relapsed subclones in two published acute myeloid leukemia patients. Furthermore, we demonstrated that through noninvasive monitoring ClonEvol recapitulated the emerging subclones throughout metastatic progression observed in the tumors of a published breast cancer patient. CONCLUSIONS: ClonEvol has broad applicability for longitudinal monitoring of clonal populations in tumor biopsies, or noninvasively, to guide precision medicine. AVAILABILITY: ClonEvol is written in R and is available at https://github.com/ChrisMaherLab/ClonEvol.

Outcomes of endoscopic ethmoidectomy performed on a day-case basis: a prospective bi-centric study.

Evaluation of endoscopic ethmoidectomy performed as a day-case in terms of security, quality, and satisfaction of the patient. This prospective observatory bi-centric study over 1 year included 74 patients undergoing an ethmoidectomy respecting the eligibility criteria of ambulatory care. We recorded patients' demographic data, operative details, satisfaction, postoperative course, and follow-up results. Nasal symptoms were evaluated by SNOT-22 on preoperative appointment and postoperatively at D30. No non-absorbable nasal packing was used, eventually in the case of preoperative-bleeding absorbable gelatine packing. The postoperative follow-up took place at D1 by phone call and at D10 and D30 to assess complications, Visual Analogue Scale, and state of ethmoidal corridors by endoscopic exam. Patients benefited of bilateral ethmoidectomy in 82.4 % cases associated with septoplasty in 42 %. The majority (95 %) was discharged on the same day. Only one patient had bleeding at D0 and was kept in standard hospitalization, such as three other patients for medical or organizational reasons not related to surgery. At D1, 23 % described postoperative light bleeding but needed no revisit and pain was estimated at 1.3 (VAS). No readmission was observed, and no major complication was noted. SNOT-22 decreased successfully by 56 %, statistically related to postoperative treatment of corticosteroids and in the case of Samter triad. 97 % of patients were satisfied of the ambulatory care. These results suggest that within an experienced and dedicated day-case medical and paramedical team, ethmoidectomy can be safely performed on a day-case basis with high quality of taking care and satisfaction of patients.