Towards respiratory muscle-protective mechanical ventilation in the critically ill: technology to monitor and assist physiology

Inadequate delivery of ventilatory assist and unphysiological respiratory drive may severely worsen respiratory muscle function in mechanically ventilated critically ill patients. Diaphragm weakness in these patients is exceedingly common (>60% of patients) and associated with poor clinical outcomes, including difficult ventilator liberation, increased risks of intensive care unit (ICU) and hospital readmission, and mortality. The underlying mechanisms of diaphragm dysfunction were extensively discussed in this thesis. Pathways primarily include the development of diaphragm disuse atrophy due to muscle inactivity or low respiratory drive (strong clinical evidence), and diaphragm injury as a result of excessive breathing effort due to insufficient ventilator assist or excessive respiratory drive (moderate evidence, mostly from experimental work). Excessive breathing effort may also worsen lung injury through pathways that include high lung stress and strain, pendelluft, increased lung perfusion, and patient-ventilator dyssynchrony. Relatively little attention has been paid to the effects of critical illness and mechanical ventilation on the expiratory muscles; however, dysfunction of these muscles has been linked to inadequate central airway clearance and extubation failure. The motivation for performing the work presented in this thesis was the hypothesis that maintaining physiological levels of respiratory muscle activity under mechanical ventilation could prevent or attenuate the development respiratory muscle weakness, and hence, improve patient outcomes. This strategy, integrated with lung-protective ventilation, was recently proposed by international experts from different professional societies (this thesis), and is referred to as a combined lung and diaphragm-protective ventilation approach. Today, an important barrier for implementing and evaluating such an approach is the lack of feasible, reliable and well-understood modalities to assess breathing effort at the bedside, as well as strategies for assisting and restoring respiratory muscle function during mechanical ventilation. Furthermore, monitoring breathing effort is crucial to identify potential relationships between patient management and detrimental respiratory (muscle) function that can be targeted to improve clinical outcomes. In this thesis we identified and improved monitoring modalities for the diaphragm (Part I), we investigated the impact of mechanical ventilation on the respiratory pump, especially the diaphragm (Part II), and we evaluated a novel strategy for maintaining expiratory muscle activity under mechanical ventilation (Part III)

Reciprocal patterning of spontaneous activity and the developing visual cortex

The connections between neurons allow information to be transported throughout the nervous system, whether this information comes from the senses or from stored memories, and whether it leads to decision making or muscle activation. Inaccurate or imprecise wiring between neurons can misroute important information, or cause over- or under-excitation of the nervous system. Connections are initially created during early development, and become fine-tuned as ‘practice’ spontaneous activity strengthens well-placed synapses and prunes aberrant connections. Spontaneous activity is generated by the developing brain itself, and can therefore encode structural information; for instance, neighbouring cells in the retina are more likely to be active at the same time than two cells that are physically further apart. This information can be passed on to other regions of the nervous system, both shaping and being shaped by the developing brain. A connection between two cells is not an all-or-nothing bridge; connections can be strong or weak, and multiple synapses can work together to have a net larger effect on a cell, increasing the likelihood of their activity being passed along. If we record high resolution images of individual neurons, we can actually see connections being formed and regulated in a living animal, with those synapses that do not play along with their neighbours being weakened and removed. In this thesis, I show that connections are preferentially maintained if they are close to other, active connections, creating high activity stretches along the dendrite. I show that the patterning of spontaneous activity relies on a specific type of inhibitory interneuron. Without the activity of these somatostatin-expressing interneurons, spontaneous activations can spread further, activating more cells and a larger proportion of the retinotopic map. Both excitatory and inhibitory activity are required to shape spontaneous activity patterns and restrict activations to a small area of the brain. As adults, we are often acutely aware of our state- whether we are stressed, attentive, or relaxed is something we can physically feel and is reflected in our neural activity. By showing that cholinergic signalling can alter the properties of spontaneous activity, we suggest that state is important even in very young animals. Finally, to causally assert the relationship between spontaneous activity and the developing brain, we developed a wireless tool that allows specific manipulation of activity patterns with minimal interference with natural animal behaviour

Inclusive search for supersymmetry using razor variables in pp collisions at root s=13 TeV

Peer reviewe

Taenia lynciscapreoli in semi-domesticated reindeer (Rangifer tarandus tarandus, L.) in Sweden

We report here Taenia lynciscapreoli metacestode from the lung lobe of a semi-domesticated reindeer (Rangifer tarandus tarandus). The specimen was detected within a development project concerning remote post mortem inspection at a reindeer abattoir in Sweden. Post mortem inspection was performed according to a routine on-site official meat inspection protocol. The species identification to T. lynciscapreoli was confirmed based on the DNA extracted from the metacestode, which was analysed by sequencing of the cytochrome c oxidase subunit 1. Firstly, our finding shows that semi-domesticated reindeer in addition to several other cervids can act as an additional intermediate host for T. lynciscapreoli. Secondly, it further confirms that this parasite is more widely distributed on the Scandinavian peninsula than what has previously been shown. This is in line with a previous molecular finding of adult T. lynciscapreoli from the Eurasian lynx (Lynx lynx) in Sweden and demonstrates that new intermediate host can be detected. Whether the present finding can be regarded as accidental or have created opportunities for an expansion throughout the northernmost Scandinavian Peninsula remains to be seen.We report here Taenia lynciscapreoli metacestode from the lung lobe of a semi-domesticated reindeer (Rangifer tarandus tarandus). The specimen was detected within a development project concerning remote post mortem inspection at a reindeer abattoir in Sweden. Post mortem inspection was performed according to a routine on-site official meat inspection protocol. The species identification to T. lynciscapreoli was confirmed based on the DNA extracted from the metacestode, which was analysed by sequencing of the cytochrome c oxidase subunit 1. Firstly, our finding shows that semi-domesticated reindeer in addition to several other cervids can act as an additional intermediate host for T. lynciscapreoli. Secondly, it further confirms that this parasite is more widely distributed on the Scandinavian peninsula than what has previously been shown. This is in line with a previous molecular finding of adult T. lynciscapreoli from the Eurasian lynx (Lynx lynx) in Sweden and demonstrates that new intermediate host can be detected. Whether the present finding can be regarded as accidental or have created opportunities for an expansion throughout the northernmost Scandinavian Peninsula remains to be seen

Toxoplasma gondii seroprevalence in reindeer (Rangifer tarandus tarandus L.) in northern Sweden: a cross-sectional study from 2014

Background Toxoplasma gondii is a parasitic protozoan that can infect a wide range of warm-blooded animals, including humans. The infection with T. gondii, is of particular concern due to its potential impact on human and animal health. In Sweden, semi-domesticated reindeer (Rangifer tarandus tarandus L.) is an important species both economically and culturally, but susceptibility to Toxoplasma infection and seroprevalence in reindeer herds remain relatively understudied.Results A total of 528 reindeer, sampled at two slaughterhouses in Sweden in 2014, were investigated for antibodies to T. gondii. Specific antibodies to T. gondii were found in 5 of 209 (2.3%) tested adult reindeer and in 6 of 308 (1.9%) tested calves, giving an apparent total prevalence of 2.1% (95% confidence interval 1.1-3.8%). None of four putative risk factors studied (sex, age, type of grazing area, county) were statistically associated with T. gondii seroprevalence.Conclusions Swedish semi-domesticated reindeer are exposed to T. gondii and may harbour infectious tissue cysts. To mitigate the risk of T. gondii infection in consumers, reindeer meat should be frozen or cooked thoroughly before consumption. The global climate change may influence the seroprevalence and possible associated risk factors for T. gondii in reindeer. To be able to manage the risk and get better advice to the consumers there is a need for further investigations covering the whole spectra of herding conditions for reindeer

Magnitude and Origin of CO2 Evasion From High-Latitude Lakes

Lakes evade significant amounts of carbon dioxide (CO2) to the atmosphere; yet the magnitude and origin of the evasion are still poorly constrained. We quantified annual CO2 evasion and its origin (in-lake net ecosystem production vs. lateral inputs from terrestrial ecosystems) in 14 high-latitude lakes through high-frequency estimates of open water CO2 flux and ecosystem metabolism and inorganic carbon mass-balance before and after ice breakup. Annual CO2 evasion ranged from 1 to 25 g C m(-2) yr(-1) of which an average of 57% was evaded over a short period at ice-breakup. Annual internal CO2 production ranged from -6 to 21 g C m(-2) yr(-1), of which at least half was produced over winter. The contribution of internal versus external source contribution to annual CO2 evasion varied between lakes, ranging from fully internal to fully external with most lakes having over 75% of the evasion sustained through a single source. Overall, the study stresses the large variability in magnitude and control of CO2 evasion and suggests that environmental change impacts on CO2 evasion from high-latitude lakes are not uniform