Exploiting Coarse Grained Parallelism in Conceptual Data Mining

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Role of queen promiscuity in reproductive swarming by honey bees

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Trends in Pediatric Patient-Ventilator Asynchrony During Invasive Mechanical Ventilation

OBJECTIVES: To explore the level and time course of patient-ventilator asynchrony in mechanically ventilated children and the effects on duration of mechanical ventilation, PICU stay, and Comfort Behavior Score as indicator for patient comfort.DESIGN: Secondary analysis of physiology data from mechanically ventilated children.SETTING: Mixed medical-surgical tertiary PICU in a university hospital.PATIENTS: Mechanically ventilated children 0-18 years old were eligible for inclusion. Excluded were patients who were unable to initiate and maintain spontaneous breathing from any cause.MEASUREMENTS AND MAIN RESULTS: Twenty-nine patients were studied with a total duration of 109 days. Twenty-two study days (20%) were excluded because patients were on neuromuscular blockade or high-frequency oscillatory ventilation, yielding 87 days (80%) for analysis. Patient-ventilator asynchrony was detected through analysis of daily recorded ventilator airway pressure, flow, and volume versus time scalars. Approximately one of every three breaths was asynchronous. The percentage of asynchronous breaths significantly increased over time, with the highest prevalence on the day of extubation. There was no correlation with the Comfort Behavior score. The percentage of asynchronous breaths during the first 24 hours was inversely correlated with the duration of mechanical ventilation. Patients with severe patient-ventilator asynchrony (asynchrony index &gt; 10% or &gt; 75th percentile of the calculated asynchrony index) did not have a prolonged duration of ventilation.CONCLUSIONS: The level of patient-ventilator asynchrony increased over time was not related to patient discomfort and inversely related to the duration of mechanical ventilation.</p

The effect of pressure support on imposed work of breathing during paediatric extubation readiness testing

BACKGROUND: Paediatric critical care practitioners often make use of pressure support (PS) to overcome the perceived imposed work of breathing (WOBimp) during an extubation readiness test (ERT). However, no paediatric data are available that shows the necessity of adding of pressure support during such tests. We sought to measure the WOBimp during an ERT with and without added pressure support and to study its clinical correlate. This was a prospective study in spontaneously breathing ventilated children < 18 years undergoing ERT. Using tracheal manometry, WOBimp was calculated by integrating the difference between positive end-expiratory pressure (PEEP) and tracheal pressure (Ptrach) over the measured expiratory tidal volume (VTe) under two paired conditions: continuous positive airway pressure (CPAP) with and without PS. Patients with post-extubation upper airway obstruction were excluded. RESULTS: A total of 112 patients were studied. Median PS during the ERT was 10 cmH2O. WOBimp was significantly higher without PS (median 0.27, IQR 0.20-0.50 J/L) than with added PS (median 0.00, IQR 0.00-0.11 J/L). Although there were statistically significant changes in spontaneous breath rate [32 (23-42) vs. 37 (27-46) breaths/min, p < 0.001] and higher ET-CO2 [5.90 (5.38-6.65) vs. 6.23 (5.55-6.94) kPa, p < 0.001] and expiratory Vt decreased [7.72 (6.66-8.97) vs. 7.08 (5.82-8.08) mL/kg, p < 0.001] in the absence of PS, these changes appeared clinically irrelevant since the Comfort B score remained unaffected [12 (10-13) vs. 12 (10-13), P = 0.987]. Multivariable analysis showed that changes in WOBimp occurred independent of endotracheal tube size. CONCLUSIONS: Withholding PS during ERT does not lead to clinically relevant increases in WOBimp, irrespective of endotracheal tube size

Driving Pressure Is Associated With Outcome in Pediatric Acute Respiratory Failure

OBJECTIVES: Driving pressure (ratio of tidal volume over respiratory system compliance) is associated with mortality in acute respiratory distress syndrome. We sought to evaluate if such association could be identified in critically ill children. DESIGN: We studied the association between driving pressure on day 1 of mechanical ventilation and ventilator-free days at day 28 through secondary analyses of prospectively collected physiology data. SETTING: Medical-surgical university hospital PICU. PATIENTS: Children younger than 18 years (stratified by Pediatric Mechanical Ventilation Consensus Conference clinical phenotype definitions) without evidence of spontaneous respiration. INTERVENTIONS: Inspiratory hold maneuvers. MEASUREMENTS AND MAIN RESULTS: Data of 222 patients with median age 11 months (2-51 mo) were analyzed. Sixty-five patients (29.3%) met Pediatric Mechanical Ventilation Consensus Conference criteria for restrictive and 78 patients (35.1%) for mixed lung disease, and 10.4% of all patients had acute respiratory distress syndrome. Driving pressure calculated by the ratio of tidal volume over respiratory system compliance for the whole cohort was 16 cm H2O (12-21 cm H2O) and correlated with the static airway pressure gradient (plateau pressure minus positive end-expiratory pressure) (Spearman correlation coefficient = 0.797; p < 0.001). Bland-Altman analysis showed that the dynamic pressure gradient (peak inspiratory pressure minus positive end-expiratory pressure) overestimated driving pressure (levels of agreement -2.295 to 7.268). Rematching the cohort through a double stratification procedure (obtaining subgroups of patients with matched mean levels for one variable but different mean levels for another ranking variable) showed a reduction in ventilator-free days at day 28 with increasing driving pressure in patients ventilated for a direct pulmonary indication. Competing risk regression analysis showed that increasing driving pressure remained independently associated with increased time to extubation (p < 0.001) after adjusting for Pediatric Risk of Mortality III 24-hour score, presence of direct pulmonary indication jury, and oxygenation index. CONCLUSIONS: Higher driving pressure was independently associated with increased time to extubation in mechanically ventilated children. Dynamic assessments of driving pressure should be cautiously interpreted

Performance of acute respiratory distress syndrome definitions in a high acuity paediatric intensive care unit

BACKGROUND: For years, paediatric critical care practitioners used the adult American European Consensus Conference (AECC) and revised Berlin Definition (BD) for acute respiratory distress syndrome (ARDS) to study the epidemiology of paediatric ARDS (PARDS). In 2015, the paediatric specific definition, Paediatric Acute Lung Injury Consensus Conference (PALICC) was developed. The use of non-invasive metrics of oxygenation to stratify disease severity were introduced in this definition, although this potentially may lead to a confounding effect of disease severity since it is more common to place indwelling arterial lines in sicker patients. We tested the hypothesis that PALICC outperforms AECC/BD in our high acuity PICU, which employs a liberal use of indwelling arterial lines and high-frequency oscillatory ventilation (HFOV). METHODS: We retrospectively collected data from children < 18 years mechanically ventilated for at least 24 h in our tertiary care, university-affiliated paediatric intensive care unit. The primary endpoint was the difference in the number of PARDS cases between AECC/BD and PALICC. Secondary endpoints included mortality and ventilator free days. Performance was assessed by the area under the receiver operating characteristics curve (AUC-ROC). RESULTS: Data from 909 out of 2433 patients was eligible for analysis. AECC/BD identified 35 (1.4%) patients (mortality 25.7%), whereas PALICC identified 135 (5.5%) patients (mortality 14.1%). All but two patients meeting AECC/Berlin criteria were also identified by PALICC. Almost half of the cohort (45.2%) had mild, 33.3% moderate and 21.5% severe PALICC PARDS at onset. Highest mortality rates were seen in patients with AECC acute lung injury (ALI)/mild Berlin and severe PALICC PARDS. The AUC-ROC for Berlin was the highest 24 h (0.392 [0.124–0.659]) after onset. PALICC showed the highest AUC-ROC at the same moment however higher than Berlin (0.531 [0.345–0.716]). Mortality rates were significantly increased in patients with bilateral consolidations (9.3% unilateral vs 26.3% bilateral, p = 0.025). CONCLUSIONS: PALICC identified more new cases PARDS than the AECC/Berlin definition. However, both PALICC and Berlin performed poorly in terms of mortality risk stratification. The presence of bilateral consolidations was associated with a higher mortality rate. Our findings may be considered in future modifications of the PALICC criteria. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s12931-021-01848-z

Highly versatile cell-penetrating peptide loaded scaffold for efficient and localised gene delivery to multiple cell types: From development to application in tissue engineering

Gene therapy has recently come of age with seven viral vector-based therapies gaining regulatory approval in recent years. In tissue engineering, non-viral vectors are preferred over viral vectors, however, lower transfection efficiencies and difficulties with delivery remain major limitations hampering clinical translation. This study describes the development of a novel multi-domain cell-penetrating peptide, GET, designed to enhance cell interaction and intracellular translocation of nucleic acids; combined with a series of porous collagen-based scaffolds with proven regenerative potential for different indications. GET was capable of transfecting cell types from all three germ layers, including stem cells, with an efficiency comparable to Lipofectamine® 3000, without inducing cytotoxicity. When implanted in vivo, GET gene-activated scaffolds allowed for host cell infiltration, transfection localized to the implantation site and sustained, but transient, changes in gene expression – demonstrating both the efficacy and safety of the approach. Finally, GET carrying osteogenic (pBMP-2) and angiogenic (pVEGF) genes were incorporated into collagen-hydroxyapatite scaffolds and with a single 2μg dose of therapeutic pDNA, induced complete repair of critical-sized bone defects within 4 weeks. GET represents an exciting development in gene therapy and by combining it with a scaffold-based delivery system offers tissue engineering solutions for a myriad of regenerative indications

The CABB dataset: A multimodal corpus of communicative interactions for behavioural and neural analyses

We present a dataset of behavioural and fMRI observations acquired in the context of humans involved in multimodal referential communication. The dataset contains audio/video and motion-tracking recordings of face-to-face, task-based communicative interactions in Dutch, as well as behavioural and neural correlates of participants’ representations of dialogue referents. Seventy-one pairs of unacquainted participants performed two interleaved interactional tasks in which they described and located 16 novel geometrical objects (i.e., Fribbles) yielding spontaneous interactions of about one hour. We share high-quality video (from three cameras), audio (from head-mounted microphones), and motion-tracking (Kinect) data, as well as speech transcripts of the interactions. Before and after engaging in the face-to-face communicative interactions, participants’ individual representations of the 16 Fribbles were estimated. Behaviourally, participants provided a written description (one to three words) for each Fribble and positioned them along 29 independent conceptual dimensions (e.g., rounded, human, audible). Neurally, fMRI signal evoked by each Fribble was measured during a one-back working-memory task. To enable functional hyperalignment across participants, the dataset also includes fMRI measurements obtained during visual presentation of eight animated movies (35 minutes total). We present analyses for the various types of data demonstrating their quality and consistency with earlier research. Besides high-resolution multimodal interactional data, this dataset includes different correlates of communicative referents, obtained before and after face-to-face dialogue, allowing for novel investigations into the relation between communicative behaviours and the representational space shared by communicators. This unique combination of data can be used for research in neuroscience, psychology, linguistics, and beyond