Veno-venal extracorporeal membrane oxygenation to support whole-lung lavage in a severe case of pulmonary alveolar proteinosis.

We present the case of a 71-year-old woman with severe bilateral primary alveolar proteinosis admitted for bilateral whole lung lavage (WLL) with a double-lumen endotracheal tube. She had a cardiac arrest of respiratory origin during the procedure and recovered after one minute of advanced resuscitation. A second LLP was scheduled under respiratory support with veno-venous extracorporeal membrane oxygenation (VV-ECMO). During this second WLL the patient was completely VV-ECMO-dependent, and the procedure was successfully completed. She was gradually weaned over the next 48 h. The patient was finally discharged after clinical improvement and home oxygen therapy was discontinued. WLL is the treatment of choice for severe cases of alveolar proteinosis. In rare cases the intervention may be poorly tolerated due to the degree of lung involvement. This case illustrates how VV-ECMO support is an option that may benefit this subgroup of at-risk patients.

Transcriptional analysis of nasal polyps fibroblasts reveals a new source of pro-inflammatory signaling in CRSwNP.

BACKGROUND: Fibroblasts and others mesenchymal cells have recently been identified as critical cells triggering tissue-specific inflammatory responses. Persistent activation of fibroblasts inflammatory program has been suggested as an underlying cause of chronic inflammation in a wide range of tissues and pathologies. Nevertheless, the role of fibroblasts in the emergence of chronic inflammation in the upper airway has not been previously addressed. We aimed to elucidate whether fibroblasts could have a role in the inflammatory response in chronic rhinosinusitis with nasal polyps (CRSwNP). METHODOLOGY: We performed whole-transcriptome microarray in fibroblast cultured from CRSwNP samples and confirmed our results by qRT-PCR. We selected patients without other associated diseases in upper airway. To investigate shifts in transcriptional profile we used fibroblasts from nasal polyps and uncinate mucosae from patient with CRSwNP, and fibroblasts from uncinate mucosae from healthy subjects as controls. RESULTS: This study exposes activation of a pro-inflammatory and pro-fibrotic transcriptional program in nasal polyps and CRSwNP fibroblasts when compared to controls. Our Gene-set Enrichment Analysis (GSEA) pointed to common up-regulation of several pro-inflammatory pathways in patients-derived fibroblasts, along with higher mRNA expression levels of cytokines, growth factors and extracellular matrix components. CONCLUSIONS: Our work reveals a potential new source of inflammatory signaling in CRSwNP. Furthermore, our results suggest that deregulated inflammatory signaling in tissue-resident fibroblasts could support a Type-2 inflammatory response. Further investigations will be necessary to demonstrate the functionality of these novel results.

Usefulness of bilateral mucoplasty plus reboot surgery in severe type-2 chronic rhinosinusitis with nasal polyps.

BACKGROUND: Although extended endoscopic sinus surgery (ESS) constitutes an alternative approach in patients with Chronic Rhinosinusitis with Nasal Polyps (CRSwNP), the surgical techniques proposed so far do not allow for an optimal control of the disease. This study introduces bilateral mucoplasty as a complementary technique to extended ESS such as reboot surgery, analyzing its benefits in healing and quality of life (QoL). METHODS: Patients diagnosed with severe Type-2 CRSwNP were selected for a prospective cohort study in two surgery groups: reboot surgery plus bilateral mucoplasty versus reboot surgery only. In the first group, an autologous endonasal mucosal graft from the nostril floor was placed bilaterally onto the ethmoidal roof. Endoscopic, radiological and QoL outcomes were compared before and one year after surgery between the two groups using Modified Lund Kennedy (LKM), Meltzer and Lund Mackay (LM) scores, and the Sino-Nasal Outcome Test 22 (SNOT-22). RESULTS: 64 patients with homogeneous baseline characteristics were included: 17 patients underwent a reboot surgery plus a bilateral mucoplasty and 47 a reboot surgery only. LKM, Meltzer and SNOT-22 scores showed significant differences before and after surgery in both groups, with higher improvement in the mucoplasty group. A greater mean improvement of 20.5 ± 6.4 points in SNOT-22 change was associated with bilateral mucoplasty. CONCLUSION: Bilateral mucoplasty plus reboot surgery constitutes a useful surgical resource in Type-2 CRSwNP patients, showing improved endoscopic, radiological and QoL outcomes one year after surgery. Further studies are needed to determine their long-term benefits.

Cinética del lactato para el pronóstico en el shock cardiogénico asistido con oxigenador extracorpóreo de membrana venoarterial / Lactate levels as a prognostic predict in cardiogenic shock under venoarterial extracorporeal membrane oxygenation support

Introducción y objetivos: El lactato y su evolución se asocian con el pronóstico de los pacientes en shock, si bien es escasa la evidencia en aquellos asistidos con oxigenador extracorpóreo de membrana venoarterial (ECMO-VA). Nuestro objetivo es evaluar su valor pronóstico en shock cardiogénico asistido con ECMO-VA. Métodos: Estudio de pacientes tratados con ECMO-VA por shock cardiogénico de indicación médica entre julio de 2013 y abril de 2021. Se calculó el aclaramiento de lactato: (lactato inicial − lactato 6 h) / lactato inicial × tiempo exacto entre ambas determinaciones. Resultados: De 121 pacientes, 44 (36,4%) tenían infarto agudo de miocardio; 42 (34,7%), implante intraparada; 14 (11,6%), tromboembolia pulmonar, 14 (11,6%), tormenta arrítmica y 6 (5,0%), miocarditis fulminante. A los 30 días habían fallecido 60 pacientes (49,6%); la mortalidad fue mayor con el implante intraparada que con el implante en circulación espontánea (30 [71,4%] de 42 frente a 30 [38,0%] de 79; p=0,030). Se asociaron de manera independiente con la mortalidad a 30 días la alanina aminotransferasa (ALT) antes del implante y el lactato (tanto basal como a las 6 h y el aclaramiento). Los modelos de regresión que incluían el lactato presentaron mejor capacidad predictiva de la supervivencia que las puntuaciones ENCOURAGE y ECMO-ACCEPTS, con mayor área bajo la curva ROC en el modelo con lactato a las 6 h.Conclusiones: El lactato (basal y a las 6 h y el aclaramiento) es un predictor independiente para el pronóstico de los pacientes en shock cardiogénico asistidos con ECMO-VA que facilita una mejor estratificación del riesgo y tiene una capacidad predictiva superior (AU)

Introduction and objectives: Lactate and its evolution are associated with the prognosis of patients in shock, although there is little evidence in those assisted with an extracorporeal venoarterial oxygenation membrane (VA-ECMO). Our objective was to evaluate its prognostic value in cardiogenic shock assisted with VA-ECMO. Methods: Study of patients with cardiogenic shock treated with VA-ECMO for medical indication between July 2013 and April 2021. Lactate clearance was calculated: [(initial lactate − 6 h lactate) / initial lactate × exact time between both determinations]. Results: From 121 patients, 44 had acute myocardial infarction (36.4%), 42 implant during cardiopulmonary resuscitation (34.7%), 14 pulmonary embolism (11.6%), 14 arrhythmic storm (11.6%), and 6 fulminant myocarditis (5.0%). After 30 days, 60 patients (49.6%) died, mortality was higher for implant during cardiopulmonary resuscitation than for implant in spontaneous circulation (30 of 42 [71.4%] vs 30 of 79 [38.0%], P=.030). Preimplantation GPT and lactate (both baseline, at 6hours, and clearance) were independently associated with 30-day mortality. The regression models that included lactate clearance had a better predictive capacity for survival than the ENCOURAGE and ECMO-ACCEPTS scores, with the area under the ROC curve being greater in the model with lactate at 6 h. Conclusions: Lactate (at baseline, 6h, and clearance) is an independent predictor of prognosis in patients in cardiogenic shock supported by VA-ECMO, allowing better risk stratification and predictive capacity (AU)

Phytotoxic Metabolites Produce by Fusarium oxysporum f. sp. cubense Race 2.

Banana is a major tropical fruit crop but banana production worldwide is seriously threatened due to Fusarium wilt. Fusarium oxysporum f. sp. cubense (Foc), the causal agent of Fusarium wilt of banana (also referred as Panama disease) is an asexual, soil inhabiting facultative parasite. Foc isolates can be classified into three races that are not defined genetically, but for their pathogenicity to different banana cultivars. Despite mycotoxins being some of the best studied virulence factors of phytopathogenic fungi and these have been useful for the prediction of Foc virulence on banana plants, toxins produced by Foc race 2 strains have not been previously identified. The aim of this contribution was to identify the phytotoxic metabolites closely related to banana wilt caused by a Foc race 2 strain. We used an in vitro bioassay on detached banana leaves to evaluate the specificity of the microbial culture filtrates before a partial purification and further identification of Foc race 2 phytotoxins. A 29-day-old host-specific culture filtrate was obtained but specificity of culture filtrate was unrecovered after partial purification. The non-specific phytotoxins were characterized as fusaric acid, beauvericin, and enniatin A. Whereas some, if not all, of these phytotoxins are important virulence factors, a proteinaceous fraction from the specific 29-day-old culture filtrate protected the leaves of the resistant banana cultivar from damage caused by such phytotoxic metabolites.

Association of airborne particulate matter with pollen, fungal spores, and allergic symptoms in an arid urbanized area.

Studies focused on the seasonal distribution of pollen and spores in semiarid cities are scarce. At these sites, climate change potentiates the emission and transport of fine (PM10) to ultrafine particles (PM2.5), easily attached to pollen surfaces, causing allergen's release. This study examines the potential correlation of seasonal variations of pollen, fungal spores, PM10, and meteorological parameters with allergic reactions of 150 people living in a Sonoran desert city. We collected PM10, airborne pollen, and spores during a year. We also studied topsoil and road dust samples as potential PM-emission sources. We obtained dust-mineralogy, chemistry, and particle size attached to pollen by X-ray diffraction and scanning electron microscope. Results show that seasonal high PM-loading in the urban atmosphere coincides with aeroallergens promoting micro- to nanoparticles' attachment to pollen's surface. A collapsed membrane was observed in several samples after individual grains show the following maximum wall coverage: Poaceae 28%, Asteraceae 40%, Chenopodiaceae-Amaranthacea 29%, Fabaceae 18%. Most of the particles covering pollen's surface have a geogenic origin mixed with metals linked to traffic (bromide, chlorine, and antimony). Mineralogical, granulometric analysis, and main wind-direction show that two local soil-types are the main contributors to PM. A high frequency of positive sensitization to pollen with high particle loading was detected. These results suggest that climate-driven dust emissions may alter pollen and spore surfaces' physicochemical characteristics with the further consequences in their allergenic potential.

Smell and Taste Dysfunction in COVID-19 Is Associated With Younger Age in Ambulatory Settings: A Multicenter Cross-Sectional Study.

BACKGROUND AND OBJECTIVE: Since the initial anecdotal reports of coronavirus disease 2019 (COVID-19) from China, a growing number of studies have reported on smell and/or taste dysfunction (STD). Objective: The aim of our study was to investigate the frequency and severity of STD in COVID-19 patients and to evaluate the association with demographic characteristics, hospital admission, symptoms, comorbidities, and blood biomarkers. METHODS: We performed a multicenter cross-sectional study on patients who were positive for SARS-CoV-2 (n=846) and controls (n=143) from 15 Spanish hospitals. Data on STD were collected prospectively using an in-person survey. The severity of STD was categorized using a visual analog scale. We analyzed time to onset, recovery rate, time to recovery, hospital admission, pneumonia, comorbidities, smoking, and symptoms. RESULTS: STD was at least 2-fold more common in COVID-19-positive patients than in controls. COVID-19-positive hospitalized patients were older, with a lower frequency of STD, and recovered earlier than outpatients. Analysis stratified by severity of STD showed that more than half of COVID-19 patients presented severe loss of smell (53.7%) or taste (52.2%); both senses were impaired in >90%. In the multivariate analysis, older age (>60 years), being hospitalized, and increased C-reactive protein were associated with a better sense of smell and/or taste. COVID-19-positive patients reported improvement in smell (45.6%) and taste (46.1%) at the time of the survey; in 90.6% this was within 2 weeks of infection. CONCLUSION: STD is a common symptom in COVID-19 and presents mainly in young and nonhospitalized patients. More studies are needed to evaluate follow-up of chemosensory impairment.

Free nasal floor mucosal grafting after endoscopic total ethmoidectomy for severe nasal polyposis: a pilot study.

BACKGROUND: We report a novel surgical technique based on an endonasal free mucosal graft (mucoplasty) for improving clinical results and local healing in chronic rhinosinusitis with nasal polyps (CRSwNP). METHODS: Patients diagnosed with bilateral CRSwNP scheduled for endoscopic sinus surgery were included. They underwent complete removal of anterior and posterior ethmoid cells, in addition to bilateral type III frontal sinusotomy. An endoscopic mucoplasty was performed in the left nasal cavity, whereas the right nasal cavity served as control. Patients were evaluated before surgery and 6 months after operation, including Sino-Nasal Outcome Test (SNOT-22), Visual Analogue Scale (VAS) for olfaction, endoscopic evaluation using the Modified und-Kennedy (MLK) scoring system and healing evaluation. RESULTS: Ten patients (mean age 53.6 years) were included. A significa t decrease of SNOT-22 score from 57.0 (21.1) to 20.3 (20.6) (P = 0.024) and a non-significa t decrease of VAS for olfaction score from 9.3 (0.5) to 4.6 (3.9) were found. Preoperative mean MLK score was 4.9 (0.7) in the right nostril and 4.8 (1.0) in the left one. After operation, there was a greater decrease of MLK score in the left nostril than in the right (1.9 [1.0] vs. 1.3 [0.8], P = 0.034). Better healing was proved in the nostril with the mucoplasty. CONCLUSION: Endonasal mucoplasty could be an effective, safe and feasible complementary surgical procedure in the treatment of CRSwNP. The reduced local edema associated with lower amount of secretions may confer a better control in the frontal recess, orbital wall and nasal roof.

NETs detection and quantification in paraffin embedded samples using confocal microscopy.

Detection and quantification of Neutrophil Extracellular Traps (NETs) in tissue samples has become a topic of great interest to understand their pathological role in various diseases. We describe a semi-automatic method of visualization and quantification of NETs in paraffin-embedded intracoronary thrombus aspirate samples. This study is based on colocalization of myeloperoxidase (MPO) and citrullinated histone 3 (H3Cit) as hallmark of the presence of NETs. For the analysis we used the confocal immunofluorescence microscopy technology to quantify the number of fields and the total area (in µm2) containing NETs in each thrombus sample. This observer-independent quantification method could be a useful tool to standardize the study of NETs in paraffin-embedded tissues, enabling comparison of results among different laboratories.

Draft Genome Sequence of a Mycobacterium africanum Clinical Isolate from Antioquia, Colombia.

Mycobacterium africanum is a member of the Mycobacterium tuberculosis complex. Most commonly found in West African countries, it has scarcely been described in South America. Here, we report the first genome sequence of a Colombian M. africanum clinical isolate. It is composed of 4,493,502 bp, with 4,069 genes.

Effect of available space and previous contact in the social integration of Saint Croix and Suffolk ewes.

Reproduction in tropical sheep is not affected by season, whereas the reproductive cycle of temperate-climate breeds such as Suffolk depends on the photoperiod. Close contact with tropical ewes during the anestrous period might induce Suffolk ewes to cycle, making the use of artificial light or hormonal treatments unnecessary. However, the integration of both breeds within the social group would be necessary to trigger this effect, and so the aim of the experiment was to determine the speed of integration of 2 groups of Saint Croix and Suffolk ewes into a single flock, according to space allowance and previous experience. For this, 6 groups of 10 ewes (half from each breed) from both breeds, housed at 2 or 4 m/ewe (3 groups/treatment) and with or without previous contact with the other breed, were monitored for 3 d. Each observation day, the behavior, movement, and use of space of ewes were collected during 10 min at 1-h intervals between 0900 and 1400 h. Generalized linear mixed models were used to test the effects of breed, space allowance, and previous experience on behavior, movement, and use of space. Net distances, interbreed farthest neighbor distance, mean interbreed distance, and walking frequencies were greater at 4 m/ewe ( < 0.05). Intrabreed nearest neighbor, mean intrabreed neighbor, and interbreed nearest neighbor distances and minimum convex polygons at 4 m/ewe were greatest for Saint Croix ewes, whereas the opposite was found for lying down ( < 0.05). Experienced ewes showed larger intrabreed nearest neighbor distances, minimum convex polygons, and home range overlapping ( < 0.05). Experienced ewes at 4 m/ewe showed longest total distances and step lengths and greatest movement activity ( < 0.05). Experienced ewes walked longer total distances during Day 1 and 2 ( < 0.05). Lying down frequency was greater for Day 3 than Day 1 ( < 0.05), and Suffolk ewes kept longer interindividual distances during Day 1 ( < 0.05). After 3 d of cohabitation, Suffolk and Saint Croix ewes did not fully integrate into a cohesive flock, with each breed displaying specific behavioral patterns. Decreasing space allowance and previous experience resulted in limited benefits for the successful group cohesion. Longer cohabitation periods might result in complete integration, although practical implementation might be difficult.

Implementación de un Demodulador Heterodino para la Discriminación del Sentido del Flujo Sanguíneo en un Detector Doppler Ultrasónico Bi-direccional / Implementation of a heterodyne demodulator for blood flow sense discrimination in a bi-directional ultrasonic Doppler detector

Los sistemas Doppler ultrasónicos han sido utilizados ampliamente en el diagnóstico médico, en general en el estudio de flujo sanguíneo y en particular en el diagnóstico de padecimientos vasculares. Esto se debe principalmente a su carácter no invasivo y su relativo bajo costo. Una característica importante de los sistemas Doppler ultrasónicos es la de poder detectar la señal asociada con el flujo sanguíneo y discriminar la dirección del mismo. La señal Doppler ultrasónica contiene información asociada con la velocidad de los componentes de la sangre, y su espectro en frecuencia representa el perfil de velocidad del flujo sanguíneo, que puede ser de sentido directo o inverso. Típicamente los sistemas Doppler ultrasónicos que detectan el sentido de la dirección de flujo sanguíneo de la señal, se basan en métodos de demodulación homodina en cuadratura. Sin embargo las señales producidas por este tipo de detectores requieren de un proceso adicional de separación. Este trabajo aborda la implementación de un demodulador heterodino que forma parte de un detector Doppler ultrasónico para la medición de flujo sanguíneo bi-direccional. Se describe el principio de la detección de la señal Doppler ultrasónica de flujo sanguíneo y su representación en la forma de un espectrograma de dos dimensiones, así como también los dispositivos detectores Doppler de flujo sanguíneo, su clasificación de acuerdo a su modo de operación y tipo de demodulación. Finalmente se presentan pruebas de funcionalidad y se analizan los resultados obtenidos contrastándolos con los resultados teóricos.

Doppler ultrasound systems have been widely used in medical diagnosis, in the study of blood flow, in particular, in the diagnosis of vascular disorders. This is mainly due to its non-invasive method and its relatively low cost. An important feature of the ultrasonic Doppler system is the capability to detect the signal associated with the blood flow and discriminate its direction. The Doppler ultrasound signal contains information associated with the velocity of the blood components, and its frequency spectrum represents the velocity profile of blood flow, which may be direct or reverse. Typically Doppler ultrasound systems which detect the sense of the direction of blood flow signal, are based on methods of homodyne demodulation in quadrature. However the signals produced by these detectors require an additional separation process. This paper addresses the implementation of a heterodyne demodulator as a part of a Doppler ultrasound detector for measuring bi-directional blood flow. We describe the detection process of the Doppler ultrasound blood flow signal and its representation in the form of a two-dimensional spectrogram. Doppler blood flow sensing devices and their classification according to their operation mode and type of demodulation are also described. Finally, functionality tests are presented and results are analyzed.

Optimización de los aislamientos preventivos en una UCI polivalente mediante la aplicación de un plan de intervención / Optimization of pre-emptive isolations in a polyvalent ICU through implementation of an intervention strategy

ANTECEDENTES: El aislamiento preventivo consiste en la aplicación de medidas de aislamiento de contacto en pacientes con alta sospecha de estar colonizados por bacterias multirresistentes. OBJETIVO: Evaluar el impacto de un programa de intervención basado en la implantación de un Protocolo Consensuado de Aislamiento Preventivo (PCAP) al ingreso en una UCI polivalente de un hospital general. MÉTODO: Análisis comparativo de 2 cohortes de pacientes, una histórica, que incluye pacientes a los que se indicó el aislamiento preventivo a juicio del médico responsable (enero de 2010 a febrero de 2011), y otra prospectiva, que incluye los pacientes a los que se aplicó el PCAP (marzo a noviembre de 2011). El PCAP incluyó la identificación y divulgación de los criterios de aislamiento preventivo, la metodología a seguir en cuanto a toma de muestras, la valoración de los resultados y los criterios de retirada del aislamiento. La indicación del aislamiento fue realizada por el personal médico, y un equipo de enfermería realizó el seguimiento. Se definió el aislamiento preventivo como «adecuado» cuando en alguna de las muestras iniciales se identificó una bacteria multirresistente. Para la comparación de resultados entre los 2 periodos se utiliza la chi cuadrado para variables cualitativas y la t de Student para variables cuantitativas. Se aceptan como significativas diferencias con p < 0,05. RESULTADOS: De los 1.740 pacientes ingresados en UCI (1.055 en el primer periodo y 685 en el segundo) se indicó el aislamiento preventivo en 199 (11,4%), de los que 111 (10,5%) correspondieron a la fase histórica (grupo control) y 88 (12,8%) a la fase posterior a la implantación del PCAP (grupo de intervención). No se han detectado diferencias en la edad, el APACHE II y las características de los pacientes entre los 2 periodos. La aplicación del PCAP se ha relacionado con una disminución de los aislamientos preventivos no indicados (29,7 vs. 6,8%, p < 0,001), una disminución del tiempo en la solicitud de las muestras de vigilancia (1,56 vs. 0,37 días, p < 0,001), y una disminución de la duración en días del aislamiento (4,77 vs. 3,58 días, p < 0,001). En 44 pacientes (22,1%) en los que se indicó el aislamiento preventivo se identificaron más de una bacteria multirresistente, siendo la tasa de «aislamiento preventivo adecuado» del 19,8% en el primer periodo y del 25,0% en el segundo (p < 0,382). CONCLUSIONES: Tras la instauración de PCAP se han reducido significativamente los aislamientos preventivos no indicados correctamente, se ha disminuido el tiempo entre el aislamiento y la toma de muestras, además de reducirse la duración del aislamiento en los casos en que no es necesario, sin que haya aumentado la tasa de «aislamiento preventivo adecuado»

BACKGROUND: Pre-emptive isolation refers to the application of contact precaution measures in patients with strongly suspected colonization by multiresistant bacteria. OBJECTIVE: To assess the impact of an intervention program involving the implementation of a consensus-based protocol of pre-emptive isolation (CPPI) on admission to a polyvalent ICU of a general hospital. METHODS: A comparative analysis of 2 patient cohorts was made: a historical cohort including patients in which pre-emptive isolation was established according to physician criterion prior to starting CPPI (from January 2010 to February 2011), and a prospective cohort including patients in which CPPI was implemented (from March to November 2011). CPPI included the identification and diffusion of pre-emptive isolation criteria, the definition of sampling methodology, the evaluation of results, and the development of criteria for discontinuation of pre-emptive isolation. Pre-emptive isolation was indicated by the medical staff, and follow-up was conducted by the nursing staff. Pre-emptive isolation was defined as "adequate" when at least one multiresistant bacteria was identified in any of the samples. Comparison of data between the 2 periods was made with the chi-square test for categorical variables and the Student t-test for quantitative variables. Statistical significance was set at P < .05. RESULTS: Among the 1,740 patients admitted to the ICU (1,055 during the first period and 685 during the second period), pre-emptive isolation was indicated in 199 (11.4%); 111 (10.5%) of these subjects corresponded to the historical cohort (control group) and 88 (12.8%) to the posterior phase after the implementation of CPPI (intervention group). No differences were found in age, APACHE II score or patient characteristics between the 2 periods. The implementation of CPPI was related to decreases in non-indicated pre-emptive isolations (29.7 vs. 6.8%, P<.001), time of requesting surveillance cultures (1.56 vs. 0.37 days, P<.001), and days of duration of treatment (4.77 vs. 3.58 days, P<.001). In 44 patients (22.1%) in which pre-emptive isolation was indicated, more than one multiresistant bacteria was identified, with an "adequate pre-emptive isolation rate” of 19.8% in the first period and 25.0% in the second period (P<.382). CONCLUSIONS: The implementation of CPPI resulted in a significant decrease in pre-emptive isolations which were not indicated correctly, a decrease in the time elapsed between isolation and collection of samples, and a decrease in the duration of isolation measures in cases in which isolation was unnecessary, without increasing the rate of "adequate pre-emptive isolation"