An astonishing regularity in student learning rate.

Leveraging a scientific infrastructure for exploring how students learn, we have developed cognitive and statistical models of skill acquisition and used them to understand fundamental similarities and differences across learners. Our primary question was why do some students learn faster than others? Or, do they? We model data from student performance on groups of tasks that assess the same skill component and that provide follow-up instruction on student errors. Our models estimate, for both students and skills, initial correctness and learning rate, that is, the increase in correctness after each practice opportunity. We applied our models to 1.3 million observations across 27 datasets of student interactions with online practice systems in the context of elementary to college courses in math, science, and language. Despite the availability of up-front verbal instruction, like lectures and readings, students demonstrate modest initial prepractice performance, at about 65% accuracy. Despite being in the same course, students' initial performance varies substantially from about 55% correct for those in the lower half to 75% for those in the upper half. In contrast, and much to our surprise, we found students to be astonishingly similar in estimated learning rate, typically increasing by about 0.1 log odds or 2.5% in accuracy per opportunity. These findings pose a challenge for theories of learning to explain the odd combination of large variation in student initial performance and striking regularity in student learning rate.

Biofragmentation of Polystyrene Microplastics: A Silent Process Performed by Chironomus sancticaroli Larvae.

Polystyrene (PS) is one of the main synthetic polymers produced around the world, and it is present in the composition of a wide variety of single-use objects. When released into the environment, these materials are degraded by environmental factors, resulting in microplastics. We investigated the ability of Chironomus sancticaroli (Diptera, Chironomidae) to promote the fragmentation of PS microspheres (24.5 ± 2.9 µm) and the toxic effects associated with exposure to this polymer. C. sancticaroli larvae were exposed to 3 different concentrations of PS (67.5, 135, and 270 particles g-1 of dry sediment) for 144 h. Significant lethality was observed only at the highest concentration. A significant reduction in PS particle size as well as evidence of deterioration on the surface of the spheres, such as grooves and cracks, was observed. In addition, changes in oxidative stress biomarkers (SOD, CAT, MDA, and GST) were also observed. This is the first study to report the ability of Chironomus sp. to promote the biofragmentation of microplastics. The information obtained demonstrates that the macroinvertebrate community can play a key role in the degradation of plastic particles present in the sediment of freshwater environments and can also be threatened by such particle pollution.

Mechanochemical hydroquinone regeneration promotes gold salt reduction in sub-stoichiometric conditions of the reducing agent.

Bottom-up mechanochemical synthesis (BUMS) has been demonstrated to be an efficient approach for the preparation of metal nanoparticles (NPs), protected by surface agents or anchored on solid supports. However, there are limitations, such as precise size and morphological control, due to a lack of knowledge about the mechanically induced processes of NP formation under milling. In this article, we further investigate the BUMS of AuNPs. Using SiO2 as a solid support, we studied the effect of typical reducing agents, namely NaBH4, L-ascorbic acid, and hydroquinone (HQ), on the conversion of a AuIII source. XANES showed that HQ is the strongest reducing agent under our experimental conditions, leading to the quantitative conversion of gold salt in a few minutes. Interestingly, even when HQ was used in sub-stoichiometric amounts, AuIII could be reduced to ratios higher than 85% after two minutes of milling. Investigations into the byproducts by 1H NMR and GC-FID/MS enabled the identification HQ regeneration and the formation of its derivatives. We mainly focused on benzoquinone (BQ), which is the product of the oxidation of HQ as it reduces the gold salt. We could demonstrate that HQ is regenerated from BQ exclusively under milling and acidic conditions. The regenerated HQ and other HQ-chlorinated molecules could then reduce gold-oxidized species, leading to higher conversions and economy of reactants. Our study highlights the intriguing and complex mechanisms of mechanochemical systems, in addition to fostering the atom and energy economy side of mechanochemical means to produce metal nanoparticles.

Scale-free movement patterns in termites emerge from social interactions and preferential attachments.

As the number or density of interacting individuals in a social group increases, a transition can develop from uncorrelated and disordered behavior of the individuals to a collective coherent pattern. We expand this observation by exploring the fine details of termite movement patterns to demonstrate that the value of the scaling exponent µ of a power law describing the Lévy walk of an individual is modified collectively as the density of animals in the group changes. This effect is absent when termites interact with inert obstacles. We also show that the network of encounters and interactions among specific individuals is selective, resembling a preferential attachment mechanism that is important for social networking. Our data strongly suggest that preferential attachments, a phenomenon not reported previously, and favorite interactions with a limited number of acquaintances are responsible for the generation of Lévy movement patterns in these social insects.

Photophysics of tz Adenine and tz Guanine fluorescent nucleobases embedded into DNA and RNA.

UV-VIS photoinduced events of tz A and tz G embedded into DNA and RNA are described by combining the Extended Multi-State Second-Order Perturbation Theory (XMS-CASPT2) and electrostatic embedding molecular mechanics methods (QM/MM). Our results point out that the S1 1 (ππ* La ) state is the bright state in both environments. After the photoexcitation to the S1 1 (ππ* La ) state, the electronic population evolves barrierless towards its minimum, from where the excess of energy can be dissipated by fluorescence. As the minimum energy crossing point structure between the ground and first bright states lies in a high-energy region, the direct internal conversion to the ground state is an unviable mechanism. Other spectroscopic properties (for instance, absorption and Stokes shifts) and comparisons with photochemical properties of canonical nucleobases are also provided.

In Search of a Molecular View of Peptide-Lipid Interactions in Membranes.

Lipid bilayer membranes are often represented as a continuous nonpolar slab with a certain thickness bounded by two more polar interfaces. Phenomena such as peptide binding to the membrane surface, folding, insertion, translocation, and diffusion are typically interpreted on the basis of this view. In this Perspective, I argue that this membrane representation as a hydrophobic continuum solvent is not adequate to understand peptide-lipid interactions. Lipids are not small compared to membrane-active peptides: their sizes are similar. Therefore, peptide diffusion needs to be understood in terms of free volume, not classical continuum mechanics; peptide solubility or partitioning in membranes cannot be interpreted in terms of hydrophobic mismatch between membrane thickness and peptide length; peptide folding and translocation, often involving cationic peptides, can only be understood if realizing that lipids adapt to the presence of peptides and the membrane may undergo considerable lipid redistribution in the process. In all of those instances, the detailed molecular interactions between the peptide residues and the lipid components are essential to understand the mechanisms involved.

Risk factors for mortality in 1528 Brazilian childhood-onset systemic lupus erythematosus patients.

OBJECTIVES: To identify associations between mortality in cSLE patients and their characteristics: clinical and laboratory features, disease activity and damage scores, and treatment; to evaluate risk factors associated with mortality in cSLE; and to determine the most frequent causes of death in this group of patients. METHODS: We performed a multicenter retrospective cohort using data from 1,528 cSLE patients followed in 27 pediatric rheumatology tertiary centers in Brazil. Patients' medical records were reviewed according to a standardized protocol, in which information regarding demographic and clinical features, disease activity and damage scores, and treatment were collected and compared between deceased cSLE patients and survivors. Univariate and multivariate analyses by Cox regression model were used to calculate risk factors for mortality, whereas survival rates were analyzed by Kaplan-Meier plots. RESULTS: A total of 63/1,528 (4.1%) patients deceased, 53/63 were female (84.1%), median age at death was 11.9 (9.4-13.1) years and median time interval between cSLE diagnosis and death was 3.2 (0.5-5.3) years. Sepsis was the main cause of death in 27/63 (42.8%) patients, followed by opportunistic infections in 7/63 (11.1%), and alveolar hemorrhage in 6/63 (9.5%) patients. The regression models resulted in neuropsychiatric lupus (NP-SLE) (HR = 2.56, 95% CI = 1.48-4.42) and chronic kidney disease (CKD) (HR = 4.33, 95% CI = 2.33-4.72), as risk factors significantly associated with mortality. Overall patient survival after cSLE diagnosis at 5, 10, and 15 years were 97%, 95.4%, and 93.8%, respectively. CONCLUSIONS: This study confirmed that the recent mortality rate in cSLE in Brazil is low, but still of concern. NP-SLE and CKD were the main risk factors for mortality, indicating that the magnitude of these manifestations was significantly high.

Chronic kidney disease in patients with childhood-onset systemic lupus erythematosus.

BACKGROUND: Lupus nephritis (LN) is a frequent manifestation of childhood-onset systemic lupus erythematosus (cSLE) with a potential risk for kidney failure and poor outcomes. This study aimed to evaluate stages III, IV, and V of chronic kidney disease (CKD) and investigate risk factors for CKD in cSLE patients. METHODS: We performed a nationwide observational cohort study in 27 pediatric rheumatology centers, including medical charts of 1528 cSLE patients. Data were collected at cSLE diagnosis, during follow-up, and at last visit or death, between September 2016 and May 2019. RESULTS: Of 1077 patients with LN, 59 (5.4%) presented with CKD, 36/59 (61%) needed dialysis, and 7/59 (11.8%) were submitted for kidney transplantation. After Bonferroni's correction for multiple comparisons (p < 0.0013), determinants associated with CKD were higher age at last visit, urinary biomarker abnormalities, neuropsychiatric involvement, higher scores of disease activity at last visit and damage index, and more frequent use of methylprednisolone, cyclosporine, cyclophosphamide, and rituximab. In the regression model analysis, arterial hypertension (HR = 15.42, 95% CI = 6.12-38.83, p ≤ 0.001) and biopsy-proven proliferative nephritis (HR = 2.83, 95%CI = 1.70-4.72, p ≤ 0.001) increased the risk of CKD, while children using antimalarials had 71.0% lower CKD risk ((1.00-0.29) × 100%) than children not using them. The Kaplan-Meier comparison showed lower survival in cSLE patients with biopsy-proven proliferative nephritis (p = 0.02) and CKD (p ≤ 0.001). CONCLUSIONS: A small number of patients manifested CKD; however, frequencies of dialysis and kidney transplantation were relevant. This study reveals that patients with cSLE with hypertension, proliferative nephritis, and absence of use of antimalarials exhibited higher hazard rates of progression to CKD. A higher resolution version of the Graphical abstract is available as Supplementary information.

Extract from Opuntia ficus-indica cladode delays the Aedes aegypti larval development by inducing an axenic midgut environment.

This study evaluated the effects of acute exposure of Aedes aegypti third instar (L3 ) larvae to the saline extract of Opuntia ficus-indica cladodes on the biological cycle and fertility of the emerging adults. For this, larvae were treated for 24 h with the extract at » LC50 (lethal concentration to kill 50% of larvae), ½ LC50 or LC50 ; the development and reproduction of the emerged adults were evaluated after a recovery period of 9 days. The resistance of proteins in the extract to hydrolysis by L3 digestive enzymes and histomorphological alterations in the larval midgut were also investigated. The extract contained lectin, flavonoids, cinnamic derivatives, terpenes, steroids, and reducing sugars. It showed a LC50 of 3.71% for 48 h. The data indicated mean survival times similar in control and extract treatments. It was observed development delay in extract-treated groups, with a lower number of adults than in control. However, the females that emerged laid similar number of eggs in control and treatments. Histological evaluation revealed absence of bacterial and fungal microorganisms in the food content in midguts from larvae treated with cladode extract. Electrophoresis revealed that three polypeptides in the extract resisted to hydrolysis by L3 digestive proteases for 90 min. The lectin activity was not altered even after 24-h incubation with the enzymes. In conclusion, the extract from O. ficus-indica can delay the development of Ae. aegypti larvae, which may be linked to induction of an axenic environment at larval midgut and permanence of lectin activity even after proteolysis.

Clinical considerations in the surgical management of peri-implantitis lesions in the esthetic zone.

OBJECTIVE: The treatment of peri-implantitis is commonly associated to soft tissue changes as part of disease resolution. These changes may alter harmony in the esthetic area, and thus may negatively affect patient satisfaction. This technical note presents the key features that may lead to an unsatisfactory esthetic outcome when managing peri-implantitis in the anterior zone. CLINICAL SIGNIFICANCE: It is essential to consider four pivotal elements in securing therapeutic success through the resolution of inflammation while maintaining esthetics: (1) patient-related factors, including patient willingness to treat and the smile line; (2) implant-related factors that influence implant position; (3) site-related factors related to defect configuration; and (4) prosthetic-related factors referred to the prosthetic emergence profile and the type of prosthesis. A comprehensive examination must be carried out preoperatively to assess the impact of the surgical treatment upon the esthetic outcomes. CONCLUSION: The clinician must be aware of the key features that condition the esthetic outcome when managing peri-implantitis.

Study of the Counter Cation Effects on the Supramolecular Structure and Electronic Properties of a Dianionic Oxamate-Based {NiII2} Helicate.

Herein, we describe the synthesis, crystal structure, and electronic properties of {[K2(dmso)(H2O)5][Ni2(H2mpba)3]·dmso·2H2O}n (1) and [Ni(H2O)6][Ni2(H2mpba)3]·3CH3OH·4H2O (2) [dmso = dimethyl sulfoxide; CH3OH = methanol; and H4mpba = 1,3-phenylenebis(oxamic acid)] bearing the [Ni2(H2mpba)3]2- helicate, hereafter referred to as {NiII2}. SHAPE software calculations indicate that the coordination geometry of all the NiII atoms in 1 and 2 is a distorted octahedron (Oh) whereas the coordination environments for K1 and K2 atoms in 1 are Snub disphenoid J84 (D2d) and distorted octahedron (Oh), respectively. The {NiII2} helicate in 1 is connected by K+ counter cations yielding a 2D coordination network with sql topology. In contrast to 1, the electroneutrality of the triple-stranded [Ni2(H2mpba)3] 2- dinuclear motif in 2 is achieved by a [Ni(H2O)6]2+ complex cation, where the three neighboring {NiII2} units interact in a supramolecular fashion through four R22(10) homosynthons yielding a 2D array. Voltammetric measurements reveal that both compounds are redox active (with the NiII/NiI pair being mediated by OH- ions) but with differences in formal potentials that reflect changes in the energy levels of molecular orbitals. The NiII ions from the helicate and the counter-ion (complex cation) in 2 can be reversibly reduced, resulting in the highest faradaic current intensities. The redox reactions in 1 also occur in an alkaline medium but at higher formal potentials. The connection of the helicate with the K+ counter cation has an impact on the energy levels of the molecular orbitals; this experimental behavior was further supported by X-ray absorption near-edge spectroscopy (XANES) experiments and computational calculations.

Social context modulates scale-free movements in a social insect.

Most animals move intermittently, pausing or slowing down for short moments and short moves, and darting away towards a new location where to hover again. This pattern occurs at a range of spatial and temporal scales (thence, resembling 'scale-free'), from the quick inspection of local areas to the sum of all movements performed from birth to death. While this pattern has been extensively described, its proximate drivers remain open to debate. A current hypothesis states that underlying proximate generative mechanisms of intermittent movement of animals are linked to external stimuli, e.g., interactions with the abiotic environment, resources, and other individuals. Here we investigated a prediction from this hypothesis, using termites as a biological model. We verified whether the social background in which a termite is inserted will modify the parameters of its intermittent scale-free spatial displacement. This relates to the hypothesis because it inspects how do external stimuli coming from intraspecifics can affect this type of movement. We tracked the trajectories of a focal termite confined along its nestmates in experimental clueless arenas, every 0.5 s along about six hours. Arenas varied in group size and comprised 22 distinct caste compositions, yielding 75 trackings (> 400 h) and more than two million Cartesian coordinates. Most of these trajectories (96% or 72/75) were classified as intermittent scale free (Lévy-like), indicating prevalence of this type of movement over non-Lévy-like ones (P=1.62×10-15). Moreover, intermittent scale-free movements performed by the focal termite (i) did arise outside the foraging-searching framework, and (ii) were modified by the social context while remaining within the limits of Lévy-walk realms. That is, some limits seem to exist along with the necessary plasticity to provide room for natural selection. Moreover, by arising outside the foraging framework, Lévy-like movements are shown to have broader relevance. Studies on processes that depend on social context and movement (e.g., collective behaviour, the spread of diseases) may, hence, profit from such concepts.

Unusual complications at the recipient site following periodontal plastic surgery procedures: a systematic review.

OBJECTIVE: To identify and describe unusual soft tissue complications of periodontal plastic surgery procedures at the recipient site after periodontal grafts. MATERIALS AND METHODS: Two independent reviewers performed a comprehensive search in MEDLINE, Cochrane, periodontics journals, reference lists, and grey literature for articles dated up to July 2021. Publications related to surgical interventions only around the teeth with an unusual complication at the recipient site were selected. No restrictions were made in the number of cases, follow-up period, or language. The Cochrane Collaboration's tool for assessing risk of bias, the Newcastle-Ottawa Scale (NOS), and two validated case report/series checklists were used to critically appraise the studies. RESULTS: A total of 1434 articles were examined, of which 28 met the inclusion criteria: one RCT, two cohort studies, and twenty-five case reports/series. The periodontal plastic surgery procedures described in these articles were conducted to treat lack of attached gingiva and gingival recessions. The following unusual complications were found: bone exostosis, epithelial inclusion, root resorption, abscess, overgrowth, "liver clot" formation, and oroantral communication. CONCLUSION: Bone exostosis and epithelial inclusions were the most prevalent unusual complications following treatment with subepithelial connective tissue graft, free gingival graft, and acellular dermal matrix allograft. Due to the nature of the reports, the clinical recommendations for diagnosis and treatment cannot be homogenized. Clinical studies reporting complications are required to develop management protocols (PROSPERO CRD42021230875). CLINICAL RELEVANCE: Clinicians need to know the main complications that can occur in mucogingival surgeries as well as their clinical management to provide a successful and predictable treatment.

A Systematic Literature Review on Distributed Machine Learning in Edge Computing.

Distributed edge intelligence is a disruptive research area that enables the execution of machine learning and deep learning (ML/DL) algorithms close to where data are generated. Since edge devices are more limited and heterogeneous than typical cloud devices, many hindrances have to be overcome to fully extract the potential benefits of such an approach (such as data-in-motion analytics). In this paper, we investigate the challenges of running ML/DL on edge devices in a distributed way, paying special attention to how techniques are adapted or designed to execute on these restricted devices. The techniques under discussion pervade the processes of caching, training, inference, and offloading on edge devices. We also explore the benefits and drawbacks of these strategies.

Diagnostic Classification of Cases of Canine Leishmaniasis Using Machine Learning.

Proposal techniques that reduce financial costs in the diagnosis and treatment of animal diseases are welcome. This work uses some machine learning techniques to classify whether or not cases of canine visceral leishmaniasis are present by physical examinations. For validation of the method, four machine learning models were chosen: K-nearest neighbor, Naïve Bayes, support vector machine and logistic regression models. The tests were performed on three hundred and forty dogs, using eighteen characteristics of the animal and the ELISA (enzyme-linked immunosorbent assay) serological test as validation. Logistic regression achieved the best metrics: Accuracy of 75%, sensitivity of 84%, specificity of 67%, a positive likelihood ratio of 2.53 and a negative likelihood ratio of 0.23, showing a positive relationship in the evaluation between the true positives and rejecting the cases of false negatives.

Accuracy of different laboratory scanners for scanning of implant-supported full arch fixed prosthesis.

OBJECTIVE: This study evaluated the accuracy of different laboratory scanners (LS) for scanning of implant-supported full arch fixed prosthesis with different implant angulations. MATERIALS AND METHODS: Two maxillary models that are designed to receive an all-on-four implant retained prosthesis were fabricated then scanned using five different LS. The models were divided into two groups according to the angulation of the posterior implant (Group 1; 30° and group 2; 45°). Each group was then subdivided into five subgroups according to the type of LS, subgroup T; Medit T710, subgroup I; IneosX5, subgroup E; 3ShapeE4, subgroup A; Autoscan DS-Mix, and subgroup M; Ceramill Map600. An industrial 3D scanner was used as reference scanner, then each model was scanned with 5 LS 10 times. Trueness and precision were analyzed using Geomagic 3D analysis software. RESULTS: Both scanner type and implant angle had a significant effect on the trueness (p < 0.001). Significant interaction was found between the scanner type and implant angle (p < 0.001). For scanner type tukeys post hoc test revealed highest trueness with the 3Shape E4 (21.3 ± 2.1) and the medit T710 (22.6 ± 2.1) and least trueness with the shining 3D autoscan ds-mix (33.8 ± 3.0). Significantly better trueness was observed with the 30° than the 45° angle. Regarding precision, two-way ANOVA revealed significant effect of the scanner type only (p < 0.001). There were no significant differences between the 3Shape E4, medit T710, Ineos X5, and the Ceramill map600. However, all showed significantly higher precision values when compared to shining 3D autoscan ds-mix. CONCLUSIONS: All tested scanners showed results within the clinically acceptable range with 3ShapeE4 and Medit T710 showing the highest accuracy. CLINICAL SIGNIFICANCE: Tested scanners can be used for scanning of All-on-four implant supported prosthesis.

Bioactive Compounds from Pale Ale Beer Powder Attenuate Experimental Colitis in BALB/c Mice.

Phenolic compounds (PCs) present in foods are associated with a decreased risk of developing inflammatory diseases. The aim of this study was to extract and characterize PCs from craft beer powder and evaluate their potential benefits in an experimental model of inflammatory bowel disease (IBD). PCs were extracted and quantified from pure beer samples. BALB/c mice received either the beer phenolic extract (BPE) or beer powder fortified with phenolic extract (BPFPE) of PCs daily for 20 days by gavage. Colon samples were collected for histopathological and immunohistochemical analyses. Dextran sodium sulfate (DSS)-induced mice lost more weight, had reduced colon length, and developed more inflammatory changes compared with DSS-induced mice treated with either BPE or BPFPE. In addition, in DSS-induced mice, the densities of CD4- and CD11b-positive cells, apoptotic rates, and activation of NF-κB and p-ERK1/2 MAPK intracellular signaling pathways were higher in those treated with BPE and BPFPE than in those not treated. Pretreatment with the phenolic extract and BPFPE remarkably attenuated DSS-induced colitis. The protective effect of PCs supports further investigation and development of therapies for human IBD.

Generalizability, transferability, and the practice-to-practice gap.

Emphasizing the predictive success and practical utility of psychological science is an admirable goal but it will require a substantive shift in how we design research. Applied research often assumes that findings are transferable to all practices, insensitive to variation between implementations. We describe efforts to quantify and close this practice-to-practice gap in education research.

Early use of nitazoxanide in mild COVID-19 disease: randomised, placebo-controlled trial.

BACKGROUND: Nitazoxanide is widely available and exerts broad-spectrum antiviral activity in vitro. However, there is no evidence of its impact on severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. METHODS: In a multicentre, randomised, double-blind, placebo-controlled trial, adult patients presenting up to 3 days after onset of coronavirus disease 2019 (COVID-19) symptoms (dry cough, fever and/or fatigue) were enrolled. After confirmation of SARS-CoV-2 infection using reverse transcriptase PCR on a nasopharyngeal swab, patients were randomised 1:1 to receive either nitazoxanide (500 mg) or placebo, three times daily, for 5 days. The primary outcome was complete resolution of symptoms. Secondary outcomes were viral load, laboratory tests, serum biomarkers of inflammation and hospitalisation rate. Adverse events were also assessed. RESULTS: From June 8 to August 20, 2020, 1575 patients were screened. Of these, 392 (198 placebo, 194 nitazoxanide) were analysed. Median (interquartile range) time from symptom onset to first dose of study drug was 5 (4-5) days. At the 5-day study visit, symptom resolution did not differ between the nitazoxanide and placebo arms. Swabs collected were negative for SARS-CoV-2 in 29.9% of patients in the nitazoxanide arm versus 18.2% in the placebo arm (p=0.009). Viral load was reduced after nitazoxanide compared to placebo (p=0.006). The percentage viral load reduction from onset to end of therapy was higher with nitazoxanide (55%) than placebo (45%) (p=0.013). Other secondary outcomes were not significantly different. No serious adverse events were observed. CONCLUSIONS: In patients with mild COVID-19, symptom resolution did not differ between nitazoxanide and placebo groups after 5 days of therapy. However, early nitazoxanide therapy was safe and reduced viral load significantly.

The Antibiotic Peptide Daptomycin Functions by Reorganizing the Membrane.

The mechanism of the antimicrobial peptide daptomycin is reviewed and discussed. Daptomycin is a last-resort antibiotic in current use against drug-resistant bacterial infections. Many models have been proposed for its function, most based on the observation that it increases membrane permeability and causes leakage of contents, such as ions and small molecules from bacterial cells and lipid vesicles. However, daptomycin is actually not efficient at permeabilizing or translocating across membranes, contrary to many well-known antimicrobial peptides. There is strong evidence that daptomycin binds preferentially to membranes in active division regions of bacterial cells and that it causes large membrane reorganization in terms of the distribution of lipids and proteins, both in cells and in model membranes. Those observations support the alternative hypothesis for the mechanism of daptomycin that its primary effect is in inducing membrane reorganization and that other events, such as increased membrane leakage and depolarization, are secondary consequences, not essential to its function.