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Early initiated noradrenaline versus fluid therapy for hypotension and shock in the emergency department (VASOSHOCK): a protocol for a pragmatic, multi-center, superiority, randomized controlled trial
No full textBackgroundShock is a condition with high mortality even with early intervention and treatment. Usual care for shock and hypotension in the Emergency Department (ED) is intravenous fluid resuscitation which can lead to fluid overload and other complications. When fluid therapy fails or risk of complications are high, the next treatment step is the use of vasopressors for stabilisation. Noradrenaline therapy for hypotension and shock are commonly used in ED’s outside Scandinavia, but the evidence on the optimal initiation time is sparse. The lack of noradrenaline therapy in Scandinavia provides a unique environment to investigate the possible implications of early initiation. The aim of this trial is to investigate whether the use of early initiated noradrenaline compared to ED fluid therapy can improve blood pressure goals and by that, reduce the need for ICU admittance.MethodsThis protocol describes a pragmatic, multi-center, superiority randomized controlled trial, randomizing patients with hypotension to intervention or control. Eligible patients are ≥ 18-year-old who have received at least 500 ml intravenous fluids (including prehospital administration), and without suspected cardiogenic, haemorrhagic, anaphylactic, or neurogenic causes, or require direct ICU admittance due to non-hemodynamic severe organ failure. The intervention group receives noradrenaline initiated at 0.05 mcg/kg/min with a maximum of 0.15 mcg/kg/min through a peripheral venous catheter for up to 24 h. The control group receives usual care. Treatment is targeted for a systolic blood pressure ≥ 100 mmHg, a mean arterial pressure ≥ 65 mmHg or a clinician defined blood pressure target. We require a sample size of 320 patients to show a significant difference in proportion of patients achieving shock control within 90 min (primary endpoint). Key secondary outcomes include ICU free days alive within 30-days and 30-day all-cause mortality.DiscussionPrevious prospective randomized trials on early peripheral noradrenaline treatment for shock are sparse and are investigated in settings where noradrenaline use is already usual care. Since noradrenaline are not used as standard treatment for shock in Scandinavian EDs, this provides a unique opportunity not only to investigate the early initiation of noradrenaline for shock, but also comparing it directly to ED fluid only approach.Trial registration: EU CT ID 2023-504584-16-00. ClinicalTrials.gov NCT05931601. URL: https://classic.clinicaltrials.gov/ct2/show/NCT0593160
How Consumer Culture Grows : The Eigendynamik of Consumption
No full textThe current climate crisis has generated social pressure to slow consumption down. Despite this, consumer culture is continuously developing and growing. How is this possible? Our paper provides theoretical clues to this question by developing a novel model of thought for consumption growth, based on Georg Simmel’s notion of Eigendynamik
Mobilising safety? Public order and the coordination of security guards in public transport in Stockholm
No full textThis study contributes to the growing literature on mobile work by examining the coordination of safety practices in public transport in Stockholm. We explore how safety, a critical and evolving theme in mobility studies, intersects with mobile work and its associated coordination challenges. Since the introduction of safety policies, security guards have focused on ‘circulatory maintenance’, a process gaining prominence in Stockholm’s public transport system. Using Suchman’s framework on centers of coordination, we identify three key practices of ‘circulatory maintenance’: coordination by education, technology and evaluation. These practices reveal that safety is not static but an ongoing, dynamic process involving formal policies, procurement efforts, and frontline workers’ situated, improvisational actions, often mediated through the ‘Safety Centre’. While these practices exhibit how mobile work is coordinated, it also signifies which efforts are put in place to ensure order in the public space that public transport is. We conclude by raising critical questions about the justification of such practices in addressing safety concerns in public transport
A Randomized Double-Blinded Clinical Study of Early Volumetric Changes After Shunt Surgery and MRI-Resistance of the Codman Certas® Plus Shunt Valve
No full textOBJECTIVE: Linear radiological measures have low sensitivity to detect changes in ventricular volume in patients with idiopathic normal pressure hydrocephalus. Ventricular volumetry is accurate and sensitive in detecting subtle changes in cerebrospinal fluid volumes. The Codman Certas® Plus is an adjustable shunt valve with 8 settings and resistant to magnetic resonance imaging (MRI)-induced inadvertent adjustments in vitro. The aim of this study was to investigate early volumetric changes in ventricles after ventriculoperitoneal shunting in relation to shunt setting and linear measures. We also wanted to evaluate the MRI-resistance of the Codman Certas® Plus valve in a clinical setting.METHODS: Forty-five idiopathic normal pressure hydrocephalus patients underwent quantitative MRI, including volumetry before and 36 hours after shunting with Codman Certas® Plus valves set to 4 (20 patients) and 8 (25 patients). Valve setting was blinded to patients and examiners and assessed after each MRI. Patients performed in total 156 MRI examinations during 3 years.RESULTS: There was significant difference in change of ventricular volume between groups 4 and 8 early after surgery. Patients with setting 4 had a ventricular volume reduction of 16 (standard deviation ± 9) mL while those with setting 8 had a reduction of 5 (standard deviation ± 5) mL. Constriction of subarachnoid cerebrospinal fluid spaces in cerebral high convexity and parafalcine sulci was significantly less in the setting 4 group postoperatively. There were no MRI-induced changes to valve setting after any MRI.CONCLUSIONS: Ventricular volumetry can detect shunt-induced reduction in ventricle volume early after surgery. The magnitude of reduction is related to shunt valve resistance. The Codman Certas® Plus valve is stable against MRI-induced changes in a clinical setting
Exploring the materiality of Anthropocene 'socionatures' : Globalised technological metabolism as intraspecific parasitism
No full textIncubation temperature shapes growth and mitochondrial metabolism across embryonic development in Japanese quail
No full textIncubation temperature affects both growth and energy metabolism in birds after hatching. Changes in cellular mechanisms, including mitochondrial function, are a likely but unexplored explanation for these effects. To test whether temperature-dependent changes to mitochondria may link embryonic development to the post-natal phenotype, we incubated Japanese quail eggs at constant low (36.0°C), medium (37.5°C) or high (39.0°C) temperature and studied mitochondrial function and growth during embryogenesis and at hatching. Embryos grew faster and had higher mitochondrial metabolism at the high incubation temperature. Low incubation temperature slowed embryonic development and decreased phosphorylating respiration but was associated with higher adenosine triphosphate production efficiency. These respiration changes were mirrored by differences in mitochondrial content, which was the lowest in cold embryos. Neither treatment affected reactive oxygen species production. Hence, improved coupling efficiency in cold embryos may have partially compensated for lower adenosine triphosphate production without increasing oxidative stress. Size differences had disappeared by hatching. However, cold-incubated chicks had a higher mitochondrial content compared with the other groups. Our study suggests that thermal suppression of embryonic metabolism may be compensated by a combination of increased coupling, longer developmental time and late-occurring upregulation of mitochondrial content. The long-term implications of these results should be studied further
Impacts of an anxiolytic drug on fish behaviour and habitat use in a natural landscape
No full textPharmaceutical contaminants reaching natural aquatic ecosystems can affect fish behaviour, modifying activity patterns, foraging behaviour and antipredator responses. While laboratory-based studies can offer key insights, assessing the ecological relevance of these findings requires field-based approaches. Therefore, we examined the effects of oxazepam, a widely prescribed anxiolytic drug, on the behaviour of a cyprinid fish (the common roach, Rutilus rutilus) in the wild, combining slow-release exposure implants with continuous tracking via acoustic telemetry. To add ecological realism, we created a landscape of fear with an uneven distribution of resources (macrophytes) and exposure to predators (pike, Esox lucius), additionally testing the effects of the drug on roach habitat selection and predator-prey interactions. Fish exposed to the drug showed an increased swimming activity and speed, but exhibited a more constrained spatial distribution in the pond, favouring areas with higher refuge availability. Both exposed and unexposed fish modified their habitat use in the presence of predators. Exposed fish appeared to get closer to the predators when these were caged, but not when predators were free-roaming. Our findings highlight the importance of considering ecological context to understand how pharmaceuticals affect fish behaviour, which is crucial for assessing risks at population and ecosystem levels
Three-dimensional co-culturing reveals human stem cell-derived somatostatin interneurons with subclass expression
No full textCortical interneuron deficiencies, particularly involving the somatostatin (SST) subtypes, contribute to neurological and neuropsychiatric disorders. These interneurons are difficult to derive in vitro from human embryonic stem cells (hESCs) due to their late embryonic development and dependence on glial interaction. To this end, we developed a three-dimensional co-culture model of hESC-derived neurons, enabling long-term development, functional maturity, and neuron-glial interaction. Under these conditions, hESCs successfully differentiated into functional GABAergic interneurons expressing the SST gene and protein within 50 days. Single-nuclei RNA sequencing revealed transcripts for SST subclasses, including Martinotti, non-Martinotti, and long-projecting neurons, that have not yet been described for hESC cultures. Upon injection into forebrain organoids, the interneuron progenitors spread and functionally matured while retaining their SST subclass identities, suggesting cell-intrinsic fate specification. Our in vitro model provides a robust platform for studying human SST interneurons, offering new avenues for investigating their role in health and disease
Rheology and dynamics of dense particle suspensions in rotary shear flows
No full textWe introduce a novel unsteady shear protocol, which we name rotary shear (RS), where the flow and vorticity directions are continuously rotated around the velocity-gradient direction by imposing two out-of-phase oscillatory shears (OSs) in orthogonal directions. We perform numerical simulations of dense suspensions of rigid non-Brownian spherical particles at volume fractions between 0.40 and 0.55, subject to this new RS protocol, and compare with the classical OS protocol. We find that the suspension viscosity displays a similar non-monotonic response as the strain amplitude is increased: a minimum viscosity is found at an intermediate, volume-fraction-dependent strain amplitude. However, the suspension dynamics is different in the new protocol. Unlike the OS protocol, suspensions under RS do not show absorbing states at any and do not undergo the reversible-irreversible transition: the stroboscopic particle dynamics is always diffusive, which we attribute to the fact that the RS protocol is inherently irreversible due to its design. To validate this hypothesis, we introduce a reversible-RS (RRS) protocol, a combination of RS and OS, where we rotate the shear direction (as in RS) until it is instantaneously reversed (as in OS), and find the resulting rheology and dynamics to be closer to OS. Detailed microstructure analysis shows that both the OS and RRS protocols result in a contact-free, isotropic to an in-contact, anisotropic microstructure at the dynamically reversible-to-irreversible transition. The RS protocol does not render such a transition, and the dynamics remains diffusive with an in-contact, anisotropic microstructure for all strain amplitudes