An experimental method to observe repetitive bubble jet collapse

Under the proper conditions, bubbles formed near a solid surface can collapse, creating a high-velocity liquid jet as the bubble implodes. These jets have the potential to damage the surfaces on which they collapse, often after only brief exposure to cavitating flow. Since cavitation damage has been observed on propellers, hydrofoils, hydro power machinery, and bubble chambers used in high energy nuclear particle detection, the concept of bubble collapse has piqued the interest of researchers across multiple industries. Most laboratory experimental attempts to create the jetting collapse rely on transient events, and measurements are hampered by the short time scale associated with the collapse, the often unpredictable position and time of the event, the small size of the cavity during the final stages of the collapse, and the self-destructiveness of the event. The purpose of this work is to develop a method to generate repetitive jet collapse and rebound at temporal and spatial scales that render measurement and observation easy. The goal is also to expand on the previously detailed experimental methods by identifying and tolerancing the key dependent variables to define a robust and repeatable procedure. The experimental set up uses an acrylic test chamber mounted on an electromagnetic shaker with variable driving frequency near 60 Hz and amplitude of up to 2 mm peak. The atmospheric pressure in the test chamber is reduced between -26 and -30 in.-hg with a vacuum pump to decouple shape and volume oscillations of the bubbles. An analog camera is positioned to record bubbles formed at the bottom surface of the containers, and the driving amplitude and frequency of the shaker is controlled by a waveform generator. A key outcome of this study was the identification of a region in the parameter space of shaker amplitude and ambient pressure where stable volumetric or ‘breathing’ oscillations could be maintained. The maximum ambient pressure with observable breathing was 27.5 in Hg of vacuum at a range of 0.2 mm to 1.2 mm of peak vertical shaker amplitude. Near -30.5 in Hg breathing was observed at smaller shaker amplitudes. The parameter space was bounded by the threshold for the rapid onset of clouds of cavitation bubbles filling large volumes of the test chamber. Repetitive jetting was observed within this region for a bubble approximately 3 mm in diameter, at 0.5 in Hg above the vapor pressure being driven at 0.3 mm amplitude at 60.1 Hz. The jetting occurred near the bottom corner and the jet angle was approximately 50 degrees from the horizontal surface. The knowledge gained from this study points the way towards achieving a more robust process to generate repetitive bubble collapse. Suggestions for improvements to the experimental setup are presented in the concluding section

Biobanking strategies in clinical trials of novel treatments

Εισαγωγή: Οι βιοτράπεζες είναι εγκαταστάσεις που συλλέγουν, επεξεργάζονται, αποθηκεύουν και διανέμουν βιολογικό υλικό και σχετικά δεδομένα, κυρίως για έρευνα. Αποτελούν έναν κρίσιμο πόρο, υποστηρίζοντας έρευνα σε τομείς όπως η ογκολογία, η γονιδιωματική και η εξατομικευμένη ιατρική, καθώς και η ανάπτυξη διαγνωστικών και θεραπευτικών μεθόδων. Το τμήμα μας αντιμετωπίζει την πρόκληση της αποθήκευσης σύνθετων δειγμάτων όπως πλασματοκύτταρα και Β λεμφοκύτταρα από αναρρόφηση μυελού των οστών. Η οργάνωση των δειγμάτων σε όλη τη ροή εργασίας της τράπεζας μπορεί να συμβάλει σημαντικά στη διατήρηση της λειτουργικής αποτελεσματικότητας και της ιχνηλασιμότητας των δειγμάτων. Μέθοδοι: Προς το παρόν η τράπεζά μας βασίζεται σε μεθόδους χειροκίνητης φόρτωσης και ανάκτησης. Η ροή εργασίας ξεκινά με τη συλλογή δειγμάτων και την επεξεργασία που είναι και οι δύο κρίσιμες κατά τη δημιουργία και την επέκταση μιας τράπεζας. Κατά τη συλλογή και επεξεργασία των δειγμάτων μας, τηρούμε αυστηρά την ορθή κλινική πρακτική (GCP) και την καλή εργαστηριακή πρακτική (GLP) προκειμένου να αποτρέψουμε προβλήματα που θα μπορούσαν να θέσουν σε κίνδυνο πολύτιμα δείγματα και να θέσουν σε κίνδυνο χρόνιας έρευνας. Αποτελέσματα (Η εμπειρία μας): Η βιοτραπεζά μας αποτελείται επί του παρόντος από δείγματα περιφερικού αίματος (πλάσμα και μονοκύτταρα) και αναρρόφησης μυελού των οστών (CD138 +, CD138-, CD19 και πλάσματος) από συγκατάθεση ασθενών με διάφορους τύπους πλασματοκυτταρικών δυσκρασιών, συμπεριλαμβανομένων ασθενών με μυέλωμα, συμπτωματικό ή ασυμμτονατικό, , μακροσφαιριναιμία Waldenstrom, αμυλοείδωση AL. Όποτε είναι δυνατόν, τα δείγματα λαμβάνονται σε διάφορα χρονικά σημεία προκειμένου να ληφθούν διαδοχικά δείγματα στην τράπεζα. Μελλοντικές προοπτικές: Εξετάζουμε τώρα τη διευκόλυνση των προβλεπόμενων ποσοστών ανάκτησης και χωρητικότητας αποθήκευσης μέσω της αυτοματοποιημένης τεχνολογίας παρακολούθησης (bar code). Σε αυτήν την περίπτωση, τα δείγματα θα επισημαίνονται με μόνιμα ανιχνεύσιμα χαρακτηριστικά που επιτρέπουν τη σάρωση και την παρακολούθηση μέσω λογισμικού διαχείρισης δεδομένων (για παράδειγμα συστήματα γραμμωτού κώδικα). Θα ενσωματώσουμε επίσης συστήματα λογισμικού για την αποθήκευση όλων των κλινικών και βιολογικών πληροφοριών που σχετίζονται με τα δείγματά μας με τη χρήση Συστημάτων Διαχείρισης Πληροφοριακών Εργαστηρίων (LIMS). Το LIMS μπορεί να ενσωματωθεί πλήρως με όλα τα όργανα στο εργαστήριο, έτσι ώστε η ροή εργασίας να είναι βελτιωμένη και πιο αποτελεσματική και όλα τα δεδομένα δοκιμών θα συλλέγονται και να αποθηκεύονται ηλεκτρονικά και με ασφάλεια με κάθε δείγμα. Στο μέλλον, ένα συγκεντρωτικό LIMS θα μας επιτρέψει να κλιμακώσουμε καθώς αυξάνεται η ζήτηση, επειδή μπορεί να διαχειριστεί όλες τις τοποθεσίες βιολογικών δειγμάτων, τη διαχείριση αιτημάτων στο διαδίκτυο, τη συμμόρφωση δεδομένων και την ασφάλεια. Συμπέρασμα: Οι βιοτράπεζες γίνονται ένας ουσιαστικός και ολοένα και πιο εξελιγμένος πόρος στη βιοϊατρική έρευνα. Οι τεχνολογικές εξελίξεις όπως ο αυτοματισμός και η μηχανοργάνωση μετασχηματίζουν τη διαχείριση των βιοτραπεζών και επιτρέπουν την εφαρμογή ολοκληρωμένων συστημάτων για τη διαχείριση δειγμάτων, δεδομένων, προσωπικού, πολιτικών και διαδικασιών για τη διανομή βιολογικών δειγμάτων και άλλων υπηρεσιών. Η τάση είναι προς μεγαλύτερες και πιο συγκεντρωτικές βιοτράπεζες, γεγονός που βελτιώνει την οικονομία της επεξεργασίας, αποθήκευσης, διανομής και ανάλυσης δεδομένων. Η ανάπτυξη τυποποιημένων διαδικασιών βασισμένων σε τεκμήρια (SOP) και η υιοθέτηση τεχνικών βέλτιστων πρακτικών, σε συνδυασμό με τη χρήση τεχνολογικών καινοτομιών σε υλικά και εξοπλισμό, μπορεί να υποστηρίξει τη δημιουργία βιοτραπεζών που κατέχουν δείγματα υψηλής ποιότητας που σχετίζονται με καλά χαρακτηρισμένα, αξιόπιστα κλινικά δεδομένα. Η ροή εργασίας από τη συλλογή δειγμάτων έως την αποθήκευση σε μια τράπεζα θα πρέπει να ικανοποιεί την πιθανότητα ότι το δείγμα πιθανότατα θα χρησιμοποιηθεί σε μια ανάλυση που δεν έχουμε ακόμα φανταστεί.Introduction: Biobanks are facilities that collect, process, store and distribute biospecimens and associated data, mainly for biological and medical research. They constitute a crucial resource, supporting cutting-edge investigation in fields such as oncology, genomics and personalised medicine, and the development of diagnostics and therapeutics. Our department is faced with the challenge of storing complex specimens such as plasma cells and B lymphocytes from bone marrow aspirates. Sample organisation throughout the biobank workflow can greatly contribute to the maintenance of operational efficiency and sample traceability. Methods: At the moment our biobank still relies on manual loading and retrieval methods. Workflow starts with sample collection and processing which are both crucial when setting up and expanding a biobank. When collecting and processing our samples, we rigorously adhere to Good Clinical Practice (GCP) and Good Laboratory Practice (GLP) in order to avert problems that could jeopardise valuable specimens and compromise years of research. Results (Our Experience): Our biobank presently consists of peripheral blood (plasma and PBMC’s) and bone marrow aspirate (CD138+, CD138-, CD19 and plasma) samples from consenting patients with various types of plasma cell dyscrasias including patients with myeloma , symptomatic or smoldering, MGUS, Waldenstrom’s macroglobulinemia , AL amyloidosis. Whenever possible, samples are taken at various time points in order to obtain sequential samples in the biobank. Future prospects: We are now looking into facilitating the intended retrieval rates and storage capacity through automated tracking technology. In this case the tubes will be labelled with permanent traceable features that enable scanning and tracking through data management software (for example barcode systems). We will also integrate software systems to store all clinical and biological information associated with our samples with the use of Laboratory Information Management Systems (LIMS). The LIMS can be fully integrated with all instruments in the lab so that workflow is improved and more efficient, and all test data will be electronically and securely compiled and stored with each sample. In the future a centralised LIMS will enable us to scale up as demand increases because it can manage all biospecimen locations, online request management, data compliance and security. Conclusion: Biobanks are becoming an essential and increasingly sophisticated resource in biomedical research. Technological advances such as automation and computerisation are transforming the management of biobanks and enabling the implementation of integrated systems to manage samples, data, personnel, policies and procedures for the distribution of biological specimens and other services. The trend is towards larger and more centralised biobanks, which improves the economics of sample processing, storage, distribution and data analysis. The development of evidence-based standard operation procedures (SOPs) and the adoption of technical best practices, in combination with the use of technological innovations in materials and equipment, can support the generation of biobanks holding high quality samples associated with well-characterised, reliable clinical data. The workflow from sample collection to storage in a biobank should accommodate the possibility that the sample will likely be used downstream in an assay that is currently not even imagined

Evidence of a Redox-Dependent Regulation of Immune Responses to Exercise-Induced Inflammation

We used thiol-based antioxidant supplementation (n-acetylcysteine, NAC) to determine whether immune mobilisation following skeletal muscle microtrauma induced by exercise is redox-sensitive in healthy humans. According to a two-trial, double-blind, crossover, repeated measures design, 10 young men received either placebo or NAC (20 mg/kg/day) immediately after a muscle-damaging exercise protocol (300 eccentric contractions) and for eight consecutive days. Blood sampling and performance assessments were performed before exercise, after exercise, and daily throughout recovery. NAC reduced the decline of reduced glutathione in erythrocytes and the increase of plasma protein carbonyls, serum TAC and erythrocyte oxidized glutathione, and TBARS and catalase activity during recovery thereby altering postexercise redox status. The rise of muscle damage and inflammatory markers (muscle strength, creatine kinase activity, CRP, proinflammatory cytokines, and adhesion molecules) was less pronounced in NAC during the first phase of recovery. The rise of leukocyte and neutrophil count was decreased by NAC after exercise. Results on immune cell subpopulations obtained by flow cytometry indicated that NAC ingestion reduced the exercise-induced rise of total macrophages, HLA+ macrophages, and 11B+ macrophages and abolished the exercise-induced upregulation of B lymphocytes. Natural killer cells declined only in PLA immediately after exercise. These results indicate that thiol-based antioxidant supplementation blunts immune cell mobilisation in response to exercise-induced inflammation suggesting that leukocyte mobilization may be under redox-dependent regulation

Personalised progression prediction in patients with monoclonal gammopathy of undetermined significance or smouldering multiple myeloma (PANGEA): a retrospective, multicohort study

BACKGROUND: Patients with precursors to multiple myeloma are dichotomised as having monoclonal gammopathy of undetermined significance or smouldering multiple myeloma on the basis of monoclonal protein concentrations or bone marrow plasma cell percentage. Current risk stratifications use laboratory measurements at diagnosis and do not incorporate time-varying biomarkers. Our goal was to develop a monoclonal gammopathy of undetermined significance and smouldering multiple myeloma stratification algorithm that utilised accessible, time-varying biomarkers to model risk of progression to multiple myeloma. METHODS: In this retrospective, multicohort study, we included patients who were 18 years or older with monoclonal gammopathy of undetermined significance or smouldering multiple myeloma. We evaluated several modelling approaches for predicting disease progression to multiple myeloma using a training cohort (with patients at Dana-Farber Cancer Institute, Boston, MA, USA; annotated from Nov, 13, 2019, to April, 13, 2022). We created the PANGEA models, which used data on biomarkers (monoclonal protein concentration, free light chain ratio, age, creatinine concentration, and bone marrow plasma cell percentage) and haemoglobin trajectories from medical records to predict progression from precursor disease to multiple myeloma. The models were validated in two independent validation cohorts from National and Kapodistrian University of Athens (Athens, Greece; from Jan 26, 2020, to Feb 7, 2022; validation cohort 1), University College London (London, UK; from June 9, 2020, to April 10, 2022; validation cohort 1), and Registry of Monoclonal Gammopathies (Czech Republic, Czech Republic; Jan 5, 2004, to March 10, 2022; validation cohort 2). We compared the PANGEA models (with bone marrow [BM] data and without bone marrow [no BM] data) to current criteria (International Myeloma Working Group [IMWG] monoclonal gammopathy of undetermined significance and 20/2/20 smouldering multiple myeloma risk criteria). FINDINGS: We included 6441 patients, 4931 (77%) with monoclonal gammopathy of undetermined significance and 1510 (23%) with smouldering multiple myeloma. 3430 (53%) of 6441 participants were female. The PANGEA model (BM) improved prediction of progression from smouldering multiple myeloma to multiple myeloma compared with the 20/2/20 model, with a C-statistic increase from 0·533 (0·480-0·709) to 0·756 (0·629-0·785) at patient visit 1 to the clinic, 0·613 (0·504-0·704) to 0·720 (0·592-0·775) at visit 2, and 0·637 (0·386-0·841) to 0·756 (0·547-0·830) at visit three in validation cohort 1. The PANGEA model (no BM) improved prediction of smouldering multiple myeloma progression to multiple myeloma compared with the 20/2/20 model with a C-statistic increase from 0·534 (0·501-0·672) to 0·692 (0·614-0·736) at visit 1, 0·573 (0·518-0·647) to 0·693 (0·605-0·734) at visit 2, and 0·560 (0·497-0·645) to 0·692 (0·570-0·708) at visit 3 in validation cohort 1. The PANGEA models improved prediction of monoclonal gammopathy of undetermined significance progression to multiple myeloma compared with the IMWG rolling model at visit 1 in validation cohort 2, with C-statistics increases from 0·640 (0·518-0·718) to 0·729 (0·643-0·941) for the PANGEA model (BM) and 0·670 (0·523-0·729) to 0·879 (0·586-0·938) for the PANGEA model (no BM). INTERPRETATION: Use of the PANGEA models in clinical practice will allow patients with precursor disease to receive more accurate measures of their risk of progression to multiple myeloma, thus prompting for more appropriate treatment strategies. FUNDING: SU2C Dream Team and Cancer Research UK

The impact of COVID-19 critical illness on new disability, functional outcomes and return to work at 6 months: a prospective cohort study

Background: There are few reports of new functional impairment following critical illness from COVID-19. We aimed to describe the incidence of death or new disability, functional impairment and changes in health-related quality of life of patients after COVID-19 critical illness at 6 months. Methods: In a nationally representative, multicenter, prospective cohort study of COVID-19 critical illness, we determined the prevalence of death or new disability at 6 months, the primary outcome. We measured mortality, new disability and return to work with changes in the World Health Organization Disability Assessment Schedule 2.0 12L (WHODAS) and health status with the EQ5D-5LTM. Results: Of 274 eligible patients, 212 were enrolled from 30 hospitals. The median age was 61 (51–70) years, and 124 (58.5%) patients were male. At 6 months, 43/160 (26.9%) patients died and 42/108 (38.9%) responding survivors reported new disability. Compared to pre-illness, the WHODAS percentage score worsened (mean difference (MD), 10.40% [95% CI 7.06–13.77]; p < 0.001). Thirteen (11.4%) survivors had not returned to work due to poor health. There was a decrease in the EQ-5D-5LTM utility score (MD, − 0.19 [− 0.28 to − 0.10]; p < 0.001). At 6 months, 82 of 115 (71.3%) patients reported persistent symptoms. The independent predictors of death or new disability were higher severity of illness and increased frailty. Conclusions: At six months after COVID-19 critical illness, death and new disability was substantial. Over a third of survivors had new disability, which was widespread across all areas of functioning.Carol L. Hodgson, Alisa M. Higgins, Michael J. Bailey, Anne M. Mather, Lisa Beach, Rinaldo Bellomo, Bernie Bissett, Ianthe J. Boden, Scott Bradley, Aidan Burrell, D. James Cooper, Bentley J. Fulcher, Kimberley J. Haines, Jack Hopkins, Alice Y. M. Jones, Stuart Lane, Drew Lawrence, Lisa van der Lee, Jennifer Liacos, Natalie J. Linke, Lonni Marques Gomes, Marc Nickels, George Ntoumenopoulos, Paul S. Myles, Shane Patman, Michelle Paton, Gemma Pound, Sumeet Rai, Alana Rix, Thomas C. Rollinson, Janani Sivasuthan, Claire J. Tipping, Peter Thomas, Tony Trapani, Andrew A. Udy, Christina Whitehead, Isabelle T. Hodgson, Shannah Anderson, Ary Serpa Neto, and The COVID-Recovery Study Investigators and the ANZICS Clinical Trials Grou

The impact of COVID-19 critical illness on new disability, functional outcomes and return to work at 6 months: a prospective cohort study

BackgroundThere are few reports of new functional impairment following critical illness from COVID-19. We aimed to describe the incidence of death or new disability, functional impairment and changes in health-related quality of life of patients after COVID-19 critical illness at 6 months.MethodsIn a nationally representative, multicenter, prospective cohort study of COVID-19 critical illness, we determined the prevalence of death or new disability at 6 months, the primary outcome. We measured mortality, new disability and return to work with changes in the World Health Organization Disability Assessment Schedule 2.0 12L (WHODAS) and health status with the EQ5D-5LTM.ResultsOf 274 eligible patients, 212 were enrolled from 30 hospitals. The median age was 61 (51–70) years, and 124 (58.5%) patients were male. At 6 months, 43/160 (26.9%) patients died and 42/108 (38.9%) responding survivors reported new disability. Compared to pre-illness, the WHODAS percentage score worsened (mean difference (MD), 10.40% [95% CI 7.06–13.77]; p TM utility score (MD, − 0.19 [− 0.28 to − 0.10]; p ConclusionsAt six months after COVID-19 critical illness, death and new disability was substantial. Over a third of survivors had new disability, which was widespread across all areas of functioning