Why is saline so acidic (and does it really matter?)

Commercial 0.9% saline solution for infusion has a pH around 5.5. There are many reasons for this acidity, some of them still obscure. It is also true that infusion of normal saline can lead to met-abolic acidaemia, yet the link between the acidity of saline solution and the acidaemia it can en-gender is not straightforward. This commentary draws together the known and putative sources of acidity in saline solutions: it turns out that the acidity of saline solution is essentially unrelated to the acidaemia complicating saline infusion.Benjamin AJ Redd

Datasheets for Machine Learning Sensors

Machine learning (ML) sensors offer a new paradigm for sensing that enables intelligence at the edge while empowering end-users with greater control of their data. As these ML sensors play a crucial role in the development of intelligent devices, clear documentation of their specifications, functionalities, and limitations is pivotal. This paper introduces a standard datasheet template for ML sensors and discusses its essential components including: the system's hardware, ML model and dataset attributes, end-to-end performance metrics, and environmental impact. We provide an example datasheet for our own ML sensor and discuss each section in detail. We highlight how these datasheets can facilitate better understanding and utilization of sensor data in ML applications, and we provide objective measures upon which system performance can be evaluated and compared. Together, ML sensors and their datasheets provide greater privacy, security, transparency, explainability, auditability, and user-friendliness for ML-enabled embedded systems. We conclude by emphasizing the need for standardization of datasheets across the broader ML community to ensure the responsible and effective use of sensor data

Widening Access to Applied Machine Learning with TinyML

Broadening access to both computational and educational resources is critical to diffusing machine-learning (ML) innovation. However, today, most ML resources and experts are siloed in a few countries and organizations. In this paper, we describe our pedagogical approach to increasing access to applied ML through a massive open online course (MOOC) on Tiny Machine Learning (TinyML). We suggest that TinyML, ML on resource-constrained embedded devices, is an attractive means to widen access because TinyML both leverages low-cost and globally accessible hardware, and encourages the development of complete, self-contained applications, from data collection to deployment. To this end, a collaboration between academia (Harvard University) and industry (Google) produced a four-part MOOC that provides application-oriented instruction on how to develop solutions using TinyML. The series is openly available on the edX MOOC platform, has no prerequisites beyond basic programming, and is designed for learners from a global variety of backgrounds. It introduces pupils to real-world applications, ML algorithms, data-set engineering, and the ethical considerations of these technologies via hands-on programming and deployment of TinyML applications in both the cloud and their own microcontrollers. To facilitate continued learning, community building, and collaboration beyond the courses, we launched a standalone website, a forum, a chat, and an optional course-project competition. We also released the course materials publicly, hoping they will inspire the next generation of ML practitioners and educators and further broaden access to cutting-edge ML technologies.Comment: Understanding the underpinnings of the TinyML edX course series: https://www.edx.org/professional-certificate/harvardx-tiny-machine-learnin

Effects of brain tissue oxygen (PbtO2) guided management on patient outcomes following severe traumatic brain injury: A systematic review and meta-analysis.

Monitoring and optimisation of brain tissue oxygen tension (PbtO2) has been associated with improved neurological outcome and survival in observational studies of severe traumatic brain injury (TBI). We carried out a systematic review of randomized controlled trials to determine if PbtO2-guided management is associated with differential neurological outcomes, survival, and adverse events. Searches were carried out to 10 February 2022 in Medline (OvidSP), 11 February in EMBASE (OvidSP) and 8 February in Cochrane library. Randomized controlled trials comparing PbtO2 and ICP-guided management to ICP-guided management alone were included. The primary outcome was survival with favourable neurological outcome at 6-months post injury. Data were extracted by two independent authors and GRADE certainty of evidence assessed. There was no difference in the proportion of patients with favourable neurological outcomes with PbtO2-guided management (relative risk [RR] 1.42, 95% CI 0.97 to 2.08; p = 0.07; I2 = 0%, very low certainty evidence) but PbtO2-guided management was associated with reduced mortality (RR 0.54, 95% CI 0.31 to 0.93; p = 0.03; I2 = 42%; very low certainty evidence) and ICP (mean difference (MD) - 4.62, 95% CI - 8.27 to - 0.98; p = 0.01; I2 = 63%; very low certainty evidence). There was no significant difference in the risk of adverse respiratory or cardiovascular events. PbtO2-guided management in addition to ICP-based care was not significantly associated with increased favourable neurological outcomes, but was associated with increased survival and reduced ICP, with no difference in respiratory or cardiovascular adverse events. However, based on GRADE criteria, the certainty of evidence provided by this meta-analysis was consistently very low. MESH: Brain Ischemia; Intensive Care; Glasgow Outcome Scale; Randomized Controlled Trial; Craniocerebral Trauma

Plasma Transfusion and Procoagulant Product Administration in Extracorporeal Membrane Oxygenation:A Secondary Analysis of an International Observational Study on Current Practices

OBJECTIVES: To achieve optimal hemostatic balance in patients on extracorporeal membrane oxygenation (ECMO), a liberal transfusion practice is currently applied despite clear evidence. We aimed to give an overview of the current use of plasma, fibrinogen concentrate, tranexamic acid (TXA), and prothrombin complex concentrate (PCC) in patients on ECMO.DESIGN: A prespecified subanalysis of a multicenter retrospective study. Venovenous (VV)-ECMO and venoarterial (VA)-ECMO are analyzed as separate populations, comparing patients with and without bleeding and with and without thrombotic complications. SETTING: Sixteen international ICUs.PATIENTS: Adult patients on VA-ECMO or VV-ECMO.INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Of 420 VA-ECMO patients, 59% (n = 247) received plasma, 20% (n = 82) received fibrinogen concentrate, 17% (n = 70) received TXA, and 7% of patients (n = 28) received PCC. Fifty percent of patients (n = 208) suffered bleeding complications and 27% (n = 112) suffered thrombotic complications. More patients with bleeding complications than patients without bleeding complications received plasma (77% vs. 41%, p &lt; 0.001), fibrinogen concentrate (28% vs 11%, p &lt; 0.001), and TXA (23% vs 10%, p &lt; 0.001). More patients with than without thrombotic complications received TXA (24% vs 14%, p = 0.02, odds ratio 1.75) in VA-ECMO, where no difference was seen in VV-ECMO. Of 205 VV-ECMO patients, 40% (n = 81) received plasma, 6% (n = 12) fibrinogen concentrate, 7% (n = 14) TXA, and 5% (n = 10) PCC. Thirty-nine percent (n = 80) of VV-ECMO patients suffered bleeding complications and 23% (n = 48) of patients suffered thrombotic complications. More patients with than without bleeding complications received plasma (58% vs 28%, p &lt; 0.001), fibrinogen concentrate (13% vs 2%, p &lt; 0.01), and TXA (11% vs 2%, p &lt; 0.01). CONCLUSIONS: The majority of patients on ECMO receive transfusions of plasma, procoagulant products, or antifibrinolytics. In a significant part of the plasma transfused patients, this was in the absence of bleeding or prolonged international normalized ratio. This poses the question if these plasma transfusions were administered for another indication or could have been avoided.</p

Widening Access to Applied Machine Learning With TinyML

Broadening access to both computational and educational resources is crit- ical to diffusing machine learning (ML) innovation. However, today, most ML resources and experts are siloed in a few countries and organizations. In this article, we describe our pedagogical approach to increasing access to applied ML through a massive open online course (MOOC) on Tiny Machine Learning (TinyML). We suggest that TinyML, applied ML on resource-constrained embedded devices, is an attractive means to widen access because TinyML leverages low-cost and globally accessible hardware and encourages the development of complete, self-contained applications, from data collection to deployment. To this end, a collaboration between academia and industry produced a four part MOOC that provides application-oriented instruction on how to develop solutions using TinyML. The series is openly available on the edX MOOC platform, has no prerequisites beyond basic programming, and is designed for global learners from a variety of backgrounds. It introduces real-world applications, ML algorithms, data-set engineering, and the ethi- cal considerations of these technologies through hands-on programming and deployment of TinyML applications in both the cloud and on their own microcontrollers. To facili- tate continued learning, community building, and collaboration beyond the courses, we launched a standalone website, a forum, a chat, and an optional course-project com- petition. We also open-sourced the course materials, hoping they will inspire the next generation of ML practitioners and educators and further broaden access to cutting-edge ML technologies

Vascular reactivity in sepsis and platelet dysfunction in septic shock.

Sepsis remains an important global cause of morbidity and mortality. Sepsis can be complicated by pathological vasodilation causing cardiovascular septic shock. The present study identifies that dysfunction of the RhoA/Rho-kinase (ROK) signalling pathway in vascular smooth muscle cells contributes to vasomotor dysfunction in sepsis. ROK inhibits myosin light chain phosphatase (MLCP) through Thr855 phosphorylation of MYPT, the L30 kDa myosin binding regulatory subunit of MLCP. MLCP dephosphorylates myosin light chain (LC₂₀) inhibiting the acto-myosin cross-bridge cycling underpinning vasoconstriction or platelet contraction. ROK dependent MLCP inhibition therefore favours vasoconstriction and can be indexed by Thr855-MYPT phosphorylation. Western blot analysis identified that Thr855 phosphorylation of MYPT was reduced in arterial segments isolated from a murine caecal ligation and puncture model of sepsis. Wire myography yielded data consistent with reduced contractile responses to thromboxane A₂ receptor stimulation, high [K⁺] mediated depolarisation and direct PKC stimulation. α₁₋ adrenergic receptor mediated vasoconstriction was similar in septic and non-septic animals, possibly reflecting the multiple mechanisms by which α₁₋ adrenergic agonists elicit vasoconstriction. Certain bacterial toxins and inflammatory mediators have the potential to attenuate ROK signaling; our data suggest therapeutic benefit of agents that promote MLCP inhibition or which vasoconstrict independent of the RhoA/ROK pathway. Current vasopressor strategies for septic shock primarily rely upon catecholamine therapy. However, there is interest in administration of vasopressin, an endogenous vasopressor inappropriately suppressed in septic shock. It is proposed that vasopressin mediates Ca²⁺ sensitisation through ROK mediated inhibition of MLCP, however, neither vasopressin dependent Ca²⁺ sensitisation nor Thr855 MYPT phosphorylation have been directly identified. In permeabilised rat caudal artery Ca²⁺ sensitisation was observed and found to depend at least partly upon PKC signaling. In contrast, stimulation with arginine vasopressin (AVP) was not associated with Thr855 MYPT phosphorylation despite the ROK inhibitor Y27632 attenuating vasopressin dependent vasoconstriction. These data support clinical evaluation of vasopressin therapy targeted to cases of septic shock arising from organisms capable of producing toxins, which neutralise RhoA/ROK. Furthermore, the data suggest either an MLCP independent vasoconstrictor role for ROK or ROK independent action of Y27632. Sepsis is also complicated by coagulopathy promoting both thrombosis and haemorrhage. Data regarding platelet function in sepsis is equivocal and absent in the specific subset of patients with septic shock. Recognising the importance of platelet contraction in thrombus formation and suggested similarities between vascular smooth muscle and platelet contraction we aimed to identify whether platelet contractile dysfunction contributed to impaired platelet aggregation in septic shock. Whole blood impedance aggregation was impaired in patients suffering from septic shock; deficits in aggregation correlated with illness severity. Impaired platelet aggregation was not associated with biochemical evidence of contractile dysfunction: neither Ser19-LC₂₀ nor Thr855-MYPT phosphorylation differed between septic shock and non-septic patients. These data indicate that therapeutic strategies to restore platelet function in septic shock might more profitably focus on platelet adhesion and secretion. These studies identify MLCP inhibition as a potential therapeutic avenue to ameliorate vascular smooth muscle, but not platelet, function in septic shock. Vasopressin might provide particularly effective vasoconstriction when targeted to cases of septic shock associated with disrupted ROK/MLCP integrity.Thesis (Ph.D.) -- University of Adelaide, School of Medical Sciences, 201