The dynamical relation between price changes and trading volume: A multidimensional clustering analysis.

This paper introduces a new method to describe and analyse multidimensional time series based on wavelets. The methodology considers the time series as observations of a functional random variable. The paper generalizes previous research on stock market networks by including asset returns and volume trading as the main variables to study the financial market. The methodology is applied to examine the dynamics and structure of the Nasdaq-100 stock market during the pandemic period 2019/12-2021/12 considering both asset returns and volume trading to model the behaviour of different assets that are part of the index, applying an algorithm that offers better performance than others applied in the clustering literature. The study detects four clusters of firms corresponding with companies sharing common economic activities. The structure of the network reveals a nonlinear relationship between the variables, and the study shows that the main macroeconomic events during the period affect each cluster with different intensity. The change in the patterns of returns and risks and the redistribution of wealth in a highly changing environment are emerging phenomena, which must necessarily be carefully analyzed by public policies, in order to avoid the appearance of bubbles and systemic shocks.

Tuning the surface charge of phospholipid bilayers inhibits insulin fibrilization.

The interactions between proteins and materials, in particular lipid bilayers, have been studied extensively for their relevance in diseases and for the formulation of protein-based therapeutics and vaccines. However, the precise rules by which material properties induce favorable or unfavorable structural states in biomolecules are incompletely understood, and as a result, the rational design of materials remains challenging. Here, we investigated the influence of lipid bilayers (in the form of small unilamellar vesicles) on the formation of insulin amyloid fibrils using a fibril-specific assay (thioflavin T), polyacrylamide gel electrophoresis, and circular dichroism spectroscopy. Lipid bilayers composed of equal mixtures of cationic and anionic lipids effectively inhibited fibril formation and stabilized insulin in its native conformation. However, other lipid bilayer compositions failed to inhibit fibril formation or even destabilized insulin, exacerbating fibrilization and/or non-amyloid aggregation. Our findings suggest that electrostatic interactions with lipid bilayers can play a critical role in stabilizing or destabilizing insulin, and preventing the conversion of insulin to its amyloidogenic, disease-associated state.

Faster Surface Ligation Reactions Improve Immobilized Enzyme Structure and Activity.

During integration into materials, the inactivation of enzymes as a result of their interaction with nanometer size denaturing "hotspots" on surfaces represents a critical challenge. This challenge, which has received far less attention than improving the long-term stability of enzymes, may be overcome by limiting the exploration of surfaces by enzymes. One way this may be accomplished is through increasing the rate constant of the surface ligation reaction and thus the probability of immobilization with reactive surface sites (i.e., ligation efficiency). Here, the connection between ligation reaction efficiency and the retention of enzyme structure and activity was investigated by leveraging the extremely fast reaction of strained trans-cyclooctene (sTCOs) and tetrazines (Tet). Remarkably, upon immobilization via Tet-sTCO chemistry, carbonic anhydrase (CA) retained 77% of its solution-phase activity, while immobilization via less efficient reaction chemistries, such as thiol-maleimide and azide-dibenzocyclooctyne, led to activity retention of only 46% and 27%, respectively. Dynamic single-molecule fluorescence tracking methods further revealed that longer surface search distances prior to immobilization (>0.5 µm) dramatically increased the probability of CA unfolding. Notably, the CA distance to immobilization was significantly reduced through the use of Tet-sTCO chemistry, which correlated with the increased retention of structure and activity of immobilized CA compared to the use of slower ligation chemistries. These findings provide an unprecedented insight into the role of ligation reaction efficiency in mediating the exploration of denaturing hotspots on surfaces by enzymes, which, in turn, may have major ramifications in the creation of functional biohybrid materials.

Mixed Phospholipid Vesicles Catalytically Inhibit and Reverse Amyloid Fibril Formation.

While many approaches to reduce fibrillation of amyloid-ß (Aß) have been aimed at slowing fibril formation, the degradation of fibrils remains challenging. We provide insight into fibril degradation as well as the inhibition of fiber formation by lipid vesicles composed of 1,2-dioleoyl-sn-glycero-3-phosphocholine and 1,2-dioleoyl-sn-glycero-3-phospho-(1'-rac-glycerol). In the presence of vesicles with the optimal lipid composition, fibril formation was inhibited up to 76%. Additionally, by tuning the lipid composition, mature fibril content decreased up to 74% and the ß-sheet content of Aß was significantly reduced. The reduction in fibril and ß-sheet content was consistent with a decrease in fibril diameter and could be attributed to the chaperone-like activity of the mixed vesicles. While demonstrating this remarkable activity, our findings present new evidence that lipid composition has a significant effect on the strength of the interaction between lipid bilayers and Aß peptides/fibrils. This understanding has intriguing therapeutic implications in treating protein misfolding diseases.

Polyelectrolyte Multilayers Enhance the Dry Storage and pH Stability of Physically Entrapped Enzymes.

Polyelectrolyte multilayers (PEMs) are attractive materials for immobilizing enzymes due to their unique ionic environment, which can prevent unfolding. Here, we demonstrated that the stability to dry storage and elevated pH were significantly enhanced when negatively charged nitroreductase (NfsB) was embedded in a PEM by depositing alternating layers of the enzyme and polycation (PC) onto porous silica particles. The PC strength (i.e., pKa) and the surface charge of the film were varied to probe the effects that internal and surface chemistry had on the pH stability of the entrapped NfsB. All films showed enhanced activity retention at elevated pH (>6), and inactivation at reduced pH (<6) similar to NfsB in solution, indicating that the primary stabilizing effect of immobilization was achieved through ionic interactions between NfsB and the PC and not through changes to the surface charge of the NfsB. Additionally, films that were stored dry at 4 °C for 1 month retained full activity, while those stored at room temperature lost 30% activity. Remarkably, at 50 °C, above the NfsB melting temperature, 40% activity was retained after 1 month of dry storage. Our results suggest that internal film properties are significantly more important than surface charge, which had minor effects on activity. Specifically, immobilization with the weak PC, poly(l-lysine), increased the optimal pH and the activity of immobilized NfsB (which we attribute to greater permeability), relative to immobilization with the strong PC, poly(diallyldimethylammonium chloride). However, NfsB was leached from the PLL film to a greater extent. Overall, these observations demonstrate that internal ionic cross-linking is key to the stabilizing effects of PEMs and that the pH response can be tuned by controlling the number of cross-links (e.g., by changing the strength of the PC). However, this may be at the cost of reduced loading, illustrating the necessity of simultaneously optimizing enzyme loading, internal ionic cross-linking, and substrate transport.

Surface-Templated Nanobubbles Protect Proteins from Surface-Mediated Denaturation.

In this Letter, we report that surface-bound nanobubbles reduce protein denaturation on methylated glass by irreversible protein shell formation. Single-molecule total internal reflection fluorescence (SM-TIRF) microscopy was combined with intramolecular Förster resonance energy transfer (FRET) to study the conformational dynamics of nitroreductase (NfsB) on nanobubble-laden methylated glass surfaces, using reflection brightfield microscopy to register nanobubble locations with NfsB adsorption. First, NfsB adsorbed irreversibly to nanobubbles with no apparent desorption after 5 h. Moreover, virtually all (96%) of the NfsB molecules that interacted with nanobubbles remained folded, whereas less than 50% of NfsB molecules remained folded in the absence of nanobubbles on unmodified silica or methylated glass surfaces. This trend was confirmed by ensemble-average fluorometer TIRF experiments. We hypothesize that nanobubbles reduce protein damage by passivating strongly denaturing topographical surface defects. Thus, nanobubble stabilization on surfaces may have important implications for antifouling surfaces and improving therapeutic protein storage.

Twinning Rates in Uruguay Between 1999 and 2015: Association with Socioeconomic and Demographic Factors.

Twinning is rare among humans, but there is much variability among populations. Several studies show that certain demographic and socioeconomic factors, such as maternal age, mother's educational level and income, influence twinning rate. There is no background of analytical studies of twins in Uruguay. To the best of our knowledge, this is the first study that has focused on describing and analyzing Uruguayan twinning rates over a period of 17 years (1999-2015). The birth data were collected from the website of Uruguay's Ministry of Public Health. Economic data were obtained from Uruguay's Instituto Nacional de Estadísti's website for the period 2001-2013, since these variables are defined specifically for that period of time. The statistical software R (The R Project for Statistical Computing) was used. The twinning rate varied from 8.51 to 13 in the studied period. Montevideo has the highest median and the smallest variability in comparison with the other departments. In Uruguay (1999-2015), the highest twinning rate (28.94%) was observed in women aged 45 and older. The analysis also showed a relationship between twin birth rates and the mother's educational level. In three regions of the country (West, Center and East), twin births show a random pattern but in the other two (North and Metropolitan), there is an increasing trend in the number of twins over time. In conclusion, this study recognizes social, economic and demographic factors that influence in the rate of twin births in Uruguay.

Risk Stratification in Patients with Complicated Parapneumonic Effusions and Empyema Using the RAPID Score.

PURPOSE: Complicated parapneumonic effusions and empyema are a leading cause of morbidity in the United States with over 1 million admissions annually and a mortality rate that remains high in spite of recent advances in diagnosis and treatment. The identification of high risk patients is crucial for improved management and the provision of cost-effective care. The RAPID score is a scoring system comprised of the following variables: renal function, age, purulence, infection source, and dietary factors and has been shown to predict outcomes in patients with pleural space infections. METHODS: In a single center retrospective study, we evaluated 98 patients with complicated parapneumonic effusions and empyema who had tube thoracostomy (with or without Intrapleural fibrinolytic therapy) and assessed treatment success rates, mortality, length of hospital stay, and direct hospitalization costs stratified by three RAPID score categories: low-risk (0-2), medium risk (3-4), and high-risk (5-7) groups. RESULTS: Treatment success rate was 71%, and the 90 day mortality rate was 12%. There was a positive-graded association between the low, medium and high RAPID score categories and mortality, (5.3%, 8.3% and 22.6%, respectively), length of hospital stay (10, 21, 19 days, respectively), and direct hospitalization costs ($19,909, $36,317 and $43,384, respectively). CONCLUSION: Our findings suggest that the RAPID score is a robust tool which could be used to identify patients with complicated parapneumonic effusions and empyema who may be at an increased risk of mortality, prolonged hospitalization, and who may incur a higher cost of treatment. Randomized controlled trials identifying the most effective initial treatment modality for medium- and high-risk patients are needed.

Stabilization of Immobilized Enzymes via the Chaperone-Like Activity of Mixed Lipid Bilayers.

Biomimetic lipid bilayers represent intriguing materials for enzyme immobilization, which is critical for many biotechnological applications. Here, through the creation of mixed lipid bilayers, the retention of immobilized enzyme structures and catalytic activity are dramatically enhanced. The enhancement in the retention of enzyme structures, which correlated with an increase in enzyme activity, is observed using dynamic single-molecule (SM) fluorescence methods. The results of SM analysis specifically show that lipid bilayers composed of mixtures of 1,2-dioleoyl- sn-glycero-3-phosphocholine (DOPC) and 1,2-dioleoyl- sn-glycero-3-phospho-(1'- rac-glycerol) (DOPG) stabilize the folded state of nitroreductase (NfsB), increasing the rate of refolding relative to unfolding of enzyme molecules on the bilayer surface. Remarkably, for optimal compositions with 15-50% DOPG, over 95% of NfsB remains folded while the activity of the enzyme is increased as much as 2 times over that in solution. Within this range of DOPG, the strength of the interaction of folded and unfolded NfsB with the bilayer surface was also significantly altered, which was evident by the change in the diffusion of folded and unfolded NfsB in the bilayer. Ultimately, these findings provide direct evidence for the chaperone-like activity of mixed DOPG/DOPC lipid bilayers, which can be controlled by tuning the fraction of DOPG in the bilayer.

An Educational Intervention Optimizes the Use of Arterial Blood Gas Determinations Across ICUs From Different Specialties: A Quality-Improvement Study.

BACKGROUND: Overuse of arterial blood gas (ABG) determinations leads to increased costs, inefficient use of staff work hours, and patient discomfort and blood loss. We developed guidelines to optimize ABG use in the ICU. METHODS: ABG use guidelines were implemented in all adult ICUs in our institution: three medical, two trauma-surgery, one cardiovascular, and one neurosurgical ICU. Although relying on pulse oximetry, we encouraged the use of ABG determination after an acute respiratory event or for a rational clinical concern and discouraged obtaining ABG measurements for routine surveillance, after planned changes of positive end-expiratory pressure or Fio2 on the mechanical ventilator, for spontaneous breathing trials, or when a disorder was not suspected. ABG measurements and global ICU metrics were collected before (year 2014) and after (year 2015) the intervention. RESULTS: We saw a reduction of 821.5 ± 257.4 ABG determinations per month (41.5%), or approximately one ABG determination per patient per mechanical ventilation (MV) day for each month (43.1%), after introducing the guidelines (P < .001). This represented 49 L of saved blood, a reduction of $39,432 in the costs of ICU care, and 1,643 staff work hours freed for other tasks. Appropriately indicated tests rose to 83.4% from a baseline 67.5% (P = .002). Less than 5% of inappropriately indicated ABG determinations changed patient management in the postintervention period. There were no significant differences in MV days, severity of illness, or ICU mortality between the two periods. CONCLUSIONS: The large scale implementation of guidelines for ABG use reduced the number of inappropriately ordered ABG determinations over seven different multidisciplinary ICUs, without negatively impacting patient care.

Follicular Lymphoma Diagnosed With Medical Thoracoscopy.

Non-Hodgkin lymphomas may present with a recurrent pleural effusion, usually with involvement of other thoracic or extrathoracic sites. Lymphomas typically presenting with pleural disease include primary effusion lymphoma and pyothorax-associated lymphoma. We describe an unusual case of recurrent pleural effusion secondary to follicular lymphoma with no other known extrathoracic involvement at the time of diagnosis.

A 66-Year-Old Man With a Past History of Relapsing Polychondritis Presented With Right Upper Lobe Consolidation, Nodular Airway Lesions, and a Corticosteroid-Responsive Chronic Cough.

A 66-year-old male nonsmoker from Arizona was referred to our practice for evaluation of chronic cough. He had a history of biopsy-proven relapsing polychondritis manifesting as right auricular and nasal pain and swelling 9 months prior to presentation. The onset of his cough coincided with the diagnosis of relapsing polychondritis, and he was prescribed prednisone 90 mg/d, which promptly relieved his rheumatologic and respiratory symptoms. A chest radiograph, obtained prior to the initiation of therapy, was normal. Any attempts at decreasing the dose of the glucocorticoid to < 30 mg/d resulted in recurrence of the cough but not of the auricular or nasal symptoms. A second chest radiograph done 6 months before presentation, while the patient was receiving prednisone 20 mg/d, was normal as well. In anticipation of our evaluation, he stopped all glucocorticoids for 7 days. He was not receiving any other medications, and he had no history of an atopic diathesis.

Pulmonary function and flow-volume loop patterns in patients with tracheobronchomalacia.

BACKGROUND: Patterns of pulmonary function tests (PFTs) and flow-volume loops among patients with clinically important tracheobronchomalacia (TBM) are not well described. Small studies suggest 4 main flow-volume loop morphologies: low maximum forced expiratory flow, biphasic expiratory curve, flow oscillations, and notching. We studied common PFT and flow-volume loop patterns among the largest prospective series of patients to date, undergoing clinical evaluation for symptomatic moderate to severe TBM. METHODS: We conducted a retrospective analysis of prospectively collected data from patients who were referred to our Chest Disease Center from January 2002 to December 2008, with respiratory symptoms that were attributed primarily to TBM. The PFT results of 90 subjects with symptomatic moderate to severe TBM were evaluated. RESULTS: By PFTs, 40 (44.4%) subjects had an obstructive ventilatory defect, 16 (17.8%) had a definite or highly likely restrictive ventilatory defect, 15 (16.7%) had a mixed defect, and 19 (21.1%) were within normal limits. Among 76 subjects with available flow-volume loops, the most frequent finding was low maximum forced expiratory flow, in 62 (81.6%) subjects, followed by biphasic morphology (15, 19.7%), notched expiratory loop (7, 9.2%), and expiratory oscillations (2, 2.6%). The balance of 13 subjects (17.1%) had no distinctive flow-volume loop abnormality. CONCLUSION: PFTs and flow-volume loops are normal in a substantial number of patients with moderate to severe TBM, and should not be used to decide whether TBM is present or clinically important.

Tumor infrecuente de pared torácica / Infrequent thoracic wall tumor

Introducción: el elastofibroma subescapular es un tumor relativamente raro de tejidos blandos. Se trata de una lesión no encapsulada y con contenido variable de colágeno, grasa y fibras elásticas. Su incidencia es variable e infrecuente. En general, es infradiagnosticado y tiene un impacto incierto, dado que debe realizarse diagnóstico diferencial con tumores subcutáneos como lipomas, fibrolipomas, formaciones quísticas o tumores más agresivos. Objetivo: poner de manifiesto la importancia del diagnóstico de estos tumores y su resección. Material y método: revisión de la bibliografía y de historias clínicas de pacientes operados de tumores de dorso. Resultados: en el período enero 2011-marzo 2012 se evaluaron 4 pacientes que consultaron por tumores en región subescapular; 3 hombres y una mujer, con una edad media de 53 años (rango, 45-64). En 3 de los casos, no tenían bilateralidad. Se estudiaron mediante exploración física, junto a la ecografía y TAC torácica, con presencia de lesión subescapular sin invasión costal o pulmonar. En todos los casos, las intervenciones se realizaron con anestesia general y se efectuó la resección completa. Los pacientes fueron dados de alta entre el 1ro y el 2do día del posoperatorio. No se registró mortalidad ni morbilidad. El diagnóstico anatomopatológico fue elastofibroma de dorso en 3 de los casos y sarcoma en el caso restante. Conclusiones: si bien se lo considera un tumor infrecuente, generalmente esto se debe a que es una patología infradiagnosticada. Se debe realizar diagnóstico diferencias con neoplasias mesenquimales tipo liposarcomas, fibrosarcomas, histiocitoma fibroso maligno o metástasis. Es por eso que el tratamiento debe ser quirúrgico dado que el diagnóstico definitivo se realiza solo con la exéresis completa de la tumoración y la malignidad no puede descartarse a menos que sea extirpado.

Introduction: The subscapular elastofibroma is a relatively rare soft-tissue tumor. It is a non-encapsulated injury with variable content of collagen, fat and elastic fibers. It has a variable and infrequent incidence. Generally, it is underdiagnosed and has an uncertain impact since differential diagnosis must be made with subcutaneous tumors such as lipomas, fibrolipomas, cystic formations or more aggressive tumors.Objective: To show the importance of diagnosing these tumors and of their resection. Material and methods: Revision of references and the medical records of patients operated of dorsi tumors. Results: Between January 2011 and March 2012, 4 patients who consulted due to tumors in the subscapular region were assessed; they were 3 men and a woman, with an average age of 53 years old (range 45-64). In 3 of the cases, there were no symptoms; only one patient declared having suffered pain. One case presented bilaterality. The patients were studied by means of physical examination, together with the ultrasound and thoracic CT scans, showing subscapular injury without costal or lung invasion. In all cases, the patients were operated with general anesthesia and complete resection was carried out. Patients were released between the 1st and 2nd day of the postoperative period. Neither mortality nor morbidity were registered. The anatomopathological analysis provided 3 cases of elastofibroma dorsi and 1 case of sarcoma.Conclusions: Although it is considered an infrequent tumor, generally, that is due to the fact that it is an underdiagnosed pathology. Differential diagnosis must be made with mesenchymal neoplasms of the type of liposarcoma, malign fibrous histiocytoma or metastasis; therefore, treatment must be surgical since the definitive diagnosis is made only with the complete extirpation of the tumor and malignity cannot be ruled out unless the extirpation has been performed.

Tumor infrecuente de pared torácica / Infrequent thoracic wall tumor

Introducción: el elastofibroma subescapular es un tumor relativamente raro de tejidos blandos. Se trata de una lesión no encapsulada y con contenido variable de colágeno, grasa y fibras elásticas. Su incidencia es variable e infrecuente. En general, es infradiagnosticado y tiene un impacto incierto, dado que debe realizarse diagnóstico diferencial con tumores subcutáneos como lipomas, fibrolipomas, formaciones quísticas o tumores más agresivos. Objetivo: poner de manifiesto la importancia del diagnóstico de estos tumores y su resección. Material y método: revisión de la bibliografía y de historias clínicas de pacientes operados de tumores de dorso. Resultados: en el período enero 2011-marzo 2012 se evaluaron 4 pacientes que consultaron por tumores en región subescapular; 3 hombres y una mujer, con una edad media de 53 años (rango, 45-64). En 3 de los casos, no tenían bilateralidad. Se estudiaron mediante exploración física, junto a la ecografía y TAC torácica, con presencia de lesión subescapular sin invasión costal o pulmonar. En todos los casos, las intervenciones se realizaron con anestesia general y se efectuó la resección completa. Los pacientes fueron dados de alta entre el 1ro y el 2do día del posoperatorio. No se registró mortalidad ni morbilidad. El diagnóstico anatomopatológico fue elastofibroma de dorso en 3 de los casos y sarcoma en el caso restante. Conclusiones: si bien se lo considera un tumor infrecuente, generalmente esto se debe a que es una patología infradiagnosticada. Se debe realizar diagnóstico diferencias con neoplasias mesenquimales tipo liposarcomas, fibrosarcomas, histiocitoma fibroso maligno o metástasis. Es por eso que el tratamiento debe ser quirúrgico dado que el diagnóstico definitivo se realiza solo con la exéresis completa de la tumoración y la malignidad no puede descartarse a menos que sea extirpado. (AU)

Introduction: The subscapular elastofibroma is a relatively rare soft-tissue tumor. It is a non-encapsulated injury with variable content of collagen, fat and elastic fibers. It has a variable and infrequent incidence. Generally, it is underdiagnosed and has an uncertain impact since differential diagnosis must be made with subcutaneous tumors such as lipomas, fibrolipomas, cystic formations or more aggressive tumors.Objective: To show the importance of diagnosing these tumors and of their resection. Material and methods: Revision of references and the medical records of patients operated of dorsi tumors. Results: Between January 2011 and March 2012, 4 patients who consulted due to tumors in the subscapular region were assessed; they were 3 men and a woman, with an average age of 53 years old (range 45-64). In 3 of the cases, there were no symptoms; only one patient declared having suffered pain. One case presented bilaterality. The patients were studied by means of physical examination, together with the ultrasound and thoracic CT scans, showing subscapular injury without costal or lung invasion. In all cases, the patients were operated with general anesthesia and complete resection was carried out. Patients were released between the 1st and 2nd day of the postoperative period. Neither mortality nor morbidity were registered. The anatomopathological analysis provided 3 cases of elastofibroma dorsi and 1 case of sarcoma.Conclusions: Although it is considered an infrequent tumor, generally, that is due to the fact that it is an underdiagnosed pathology. Differential diagnosis must be made with mesenchymal neoplasms of the type of liposarcoma, malign fibrous histiocytoma or metastasis; therefore, treatment must be surgical since the definitive diagnosis is made only with the complete extirpation of the tumor and malignity cannot be ruled out unless the extirpation has been performed. (AU)

A 24-year-old man with cough, rhabdomyolysis, and pneumomediastinum.

BACKGROUND: Community-acquired methicillin-resistant Staphylococcus aureus (CA-MRSA) frequently causes severe necrotizing pneumonia in young patients. CASE: We present the case of a 24-year-old male, who was brought to the emergency department with persistent fevers, confusion, and severe cough. He was found to have necrotizing pneumonia, pneumomediastinum, and rhabdomyolysis with renal failure. Cultures were positive for influenza A and CA-MRSA. After a prolonged intensive care unit (ICU) stay, he made a complete recovery. CONCLUSION: Community-acquired MRSA pneumonia is a growing health threat that typically presents in young adults after, or in conjunction with, a flu-like illness. It is characterized by a rapidly progressive deteriorating clinical course.