Depth, Highness and DNR degrees

We study Bennett deep sequences in the context of recursion theory; in particular we investigate the notions of O(1)-deepK, O(1)-deepC , order-deep K and order-deep C sequences. Our main results are that Martin-Loef random sets are not order-deepC , that every many-one degree contains a set which is not O(1)-deepC , that O(1)-deepC sets and order-deepK sets have high or DNR Turing degree and that no K-trival set is O(1)-deepK.Comment: journal version, dmtc

Depth, Highness and DNR Degrees

A sequence is Bennett deep [5] if every recursive approximation of the Kolmogorov complexity of its initial segments from above satisfies that the difference between the approximation and the actual value of the Kolmogorov complexity of the initial segments dominates every constant function. We study for different lower bounds r of this difference between approximation and actual value of the initial segment complexity, which properties the corresponding r(n)-deep sets have. We prove that for r(n) = εn, depth coincides with highness on the Turing degrees. For smaller choices of r, i.e., r is any recursive order function, we show that depth implies either highness or diagonally-non-recursiveness (DNR). In particular, for left-r.e. sets, order depth already implies highness. As a corollary, we obtain that weakly-useful sets are either high or DNR. We prove that not all deep sets are high by constructing a low order-deep set. Bennett's depth is defined using prefix-free Kolmogorov complexity. We show that if one replaces prefix-free by plain Kolmogorov complexity in Bennett's depth definition, one obtains a notion which no longer satisfies the slow growth law (which stipulates that no shallow set truth-table computes a deep set); however, under this notion, random sets are not deep (at the unbounded recursive order magnitude). We improve Bennett's result that recursive sets are shallow by proving all K-trivial sets are shallow; our result is close to optimal. For Bennett's depth, the magnitude of compression improvement has to be achieved almost everywhere on the set. Bennett observed that relaxing to infinitely often is meaningless because every recursive set is infinitely often deep. We propose an alternative infinitely often depth notion that doesn't suffer this limitation (called i.o. depth).We show that every hyperimmune degree contains a i.o. deep set of magnitude εn, and construct a π01- class where every member is an i.o. deep set of magnitude εn. We prove that every non-recursive, non-DNR hyperimmune-free set is i.o. deep of constant magnitude, and that every nonrecursive many-one degree contains such a set

Resistance profiles and genetic diversity of Escherichia coli strains isolated from acute bovine mastitis

Between March 2011 and February 2012 83 E. coli strains were isolated from mastitis milk samples from 83 different animals (67 farms) and tested for their sensitivity to various antibiotics by means of disk diffusion method and genotyped by determination of the phylogenetic groups as well as by pulsed field gel electrophoresis (PFGE). The antibiotics were chosen on the basis of their licenses for intramammary application in Switzerland. As many as 16.9 % of the isolates were resistant to one or more antimicrobial agents. Amoxicillin-clavulanic acid, gentamicin and third generation cephalosporins proved effective against the majority of these strains. Nevertheless, one blaCTX-M-14 harbouring extended-spectrum-beta-lactamase producing strain was found. Genetic analysis grouped most of the strains (87 %) into phylogenetic groups A and B1. PFGE genotyping demonstrated that E. coli from cows with mastitis even from the same farm were genotypically very diverse. = Entre mars 2011 et février 2012, 83 souches d'E. coli issues de 83 vaches différentes provenant de 67 exploitations ont été collectées et testées quant à leur sensibilité vis-à-vis de divers antibiotiques. Ces antibiotiques ont été choisis sur la base de leurs autorisations pour l'application intra mammaire en Suisse et le test a été effectué par diffusion sur gel d'agar. En outre toutes les souches ont été typisées quant à leur appartenance aux groupes phylogénétiques. 16.9 % des souches présentaient une résistance à un ou plusieurs antibiotiques. L'amoxicilline-acide clavulanique, la gentamicine et les céphalosporines de troisièmes générations se montraient efficaces contre la majorité des souches d'E. coli. On a toutefois trouvé une souche fabriquant un extended-spectrum-beta-lactamase qui portait le gène blaCTX-M-14. L'analyse génétique groupait la majorité des souches (87 %) dans les groupes phylogénétiques A et B1. La génotypisation par PFGE montrait une grande diversité entre les souches, même si elles provenaient de la même exploitation. = Zwischen März 2011 und Februar 2012 wurden 83 E. coli Stämme von 83 verschiedenen Kühen aus 67 Betrieben gesammelt und auf ihre Empfindlichkeit gegenüber verschiedenen Antibiotika getestet. Die Antibiotika wurden aufgrund der Zulassung für eine intramammäre Applikation in der Schweiz ausgesucht und die Empfindlichkeitstestung mittels Agardiffusions-Methode durchgeführt. Zudem wurden alle Stämme hinsichtlich ihrer Zugehörigkeit zu den phylogenetischen Gruppen wie auch mittels Pulsfeldgelelektrophorese (PFGE) genotypisiert. 16.9 % aller Stämme zeigten Resistenzen gegenüber einem oder mehreren Antibiotika. Amoxicillin-Clavulansäure, Gentamicin und Cephalosporine der dritten Generation erwiesen sind als wirksam gegen die Mehrheit der E. coli Stämme. Jedoch wurde ein extended-Spectrum-beta-Lactamase Bildner, welcher das blaCTX-M-14-Gen trägt, gefunden. Die genetische Analyse gruppierte das Gros der Stämme (87 %) in die phylogentischen Guppen A und B1. Die weitere Genotypisierung mittels PFGE zeigte eine grosse Diversität unter den E. coli Stämmen, auch wenn diese vom selben Betrieb stammten

The Impact of Exercise on Telomere Length, DNA Methylation and Metabolic Footprints

Aging as a major risk factor influences the probability of developing cancer, cardiovascular disease and diabetes, amongst others. The underlying mechanisms of disease are still not fully understood, but research suggests that delaying the aging process could ameliorate these pathologies. A key biological process in aging is cellular senescence which is associated with several stressors such as telomere shortening or enhanced DNA methylation. Telomere length as well as DNA methylation levels can be used as biological age predictors which are able to detect excessive acceleration or deceleration of aging. Analytical methods examining aging are often not suitable, expensive, time-consuming or require a high level of technical expertise. Therefore, research focusses on combining analytical methods which have the potential to simultaneously analyse epigenetic, genomic as well as metabolic changes

Targeting thromboinflammation in COVID-19 - A narrative review of the potential of C1 inhibitor to prevent disease progression.

Coronavirus disease 2019 (COVID-19) caused by SARS-CoV-2 is associated with a clinical spectrum ranging from asymptomatic carriers to critically ill patients with complications including thromboembolic events, myocardial injury, multisystemic inflammatory syndromes and death. Since the beginning of the pandemic several therapeutic options emerged, with a multitude of randomized trials, changing the medical landscape of COVID-19. The effect of various monoclonal antibodies, antiviral, anti-inflammatory and anticoagulation drugs have been studied, and to some extent, implemented into clinical practice. In addition, a multitude of trials improved the understanding of the disease and emerging evidence points towards a significant role of the complement system, kallikrein-kinin, and contact activation system as drivers of disease in severe COVID-19. Despite their involvement in COVID-19, treatments targeting these plasmatic cascades have neither been systematically studied nor introduced into clinical practice, and randomized studies with regards to these treatments are scarce. Given the multiple-action, multiple-target nature of C1 inhibitor (C1-INH), the natural inhibitor of these cascades, this drug may be an interesting candidate to prevent disease progression and combat thromboinflammation in COVID-19. This narrative review will discuss the current evidence with regards to the involvement of these plasmatic cascades as well as endothelial cells in COVID-19. Furthermore, we summarize the evidence of C1-INH in COVID-19 and potential benefits and pitfalls of C1-INH treatment in COVID-19

Effect of the inhibition of CYP3A4 or CYP2D6 on the pharmacokinetics and pharmacodynamics of oxycodone

Purpose: The main metabolic pathways of oxycodone, a potent opioid analgetic, are N-demethylation (CYP3A4) to inactive noroxycodone and O-demethylation (CYP2D6) to active oxymorphone. We performed a three-way, placebo-controlled, double-blind cross-over study to assess the pharmacokinetic and pharmacodynamic consequences of drug interactions with oxycodone. Methods: The 12 participants (CYP2D6 extensive metabolizers) were pre-treated with placebo, ketoconazole or paroxetine before oral oxycodone ingestion (0.2mg/kg). Results: Pre-treatment with ketoconazole increased the AUC for oxycodone 2- to 3-fold compared with placebo or paroxetine. In combination with placebo, oxycodone induced the expected decrease in pupil diameter. This decrease was accentuated in the presence of ketoconazole, but blunted by paroxetine. In comparison to pre-treatment with placebo, ketoconazole increased nausea, drowsiness, and pruritus associated with oxycodone. In contrast, the effect of pre-treatment with paroxetine on the above-mentioned adverse events was not different from that of placebo. Ketoconazole increased the analgetic effect of oxycodone, whereas paroxetine was not different from placebo. Conclusions: Inhibition of CYP3A4 by ketoconazole increases the exposure and some pharmacodynamic effects of oxycodone. Paroxetine pretreatment inhibits CYP2D6 without inducing relevant changes in oxycodone exposure, and partially blunts the pharmacodynamic effects of oxycodone due to intrinsic pharmacological activities. Pharmacodynamic changes associated with CYP3A4 inhibition may be clinically important in patients treated with oxycodon

Metal Mining's Environmental Pressures: A Review and Updated Estimates on CO2 Emissions, Water Use, and Land Requirements

The significant increase in metal mining and the inevitability of the continuation of this trend suggests that environmental pressures, as well as related impacts, have become an issue of global relevance. Yet the scale of the impact remains, to a large extent, unknown. This paper examines the mining sector's demands on CO2 emissions, water use, as well as demands on land use focusing on four principal metals: iron, aluminium (i.e., bauxite ore), copper, and gold. These materials represent a large proportion of all metallic materials mined in terms of crude tonnage and economic value. This paper examines how the main providers of mining data, the United Nations, government sources of some main metal producing and consuming countries, the scientific literature, and company reports report environmental pressures in these three areas. The authors conclude that, in the global context, the pressure brought about by metal mining is relatively low. The data on this subject are still very limited and there are significant gaps in consistency on criteria such as boundary descriptions, input parameter definitions, and allocation method descriptions as well as a lack of commodity and/or site specific reporting of environmental data at a company level

Impact of cardiac surgery and neurosurgery patients on variation in severity-adjusted resource use in intensive care units

Publisher Copyright: © 2022Purpose: The resource use of cardiac surgery and neurosurgery patients likely differ from other ICU patients. We evaluated the relevance of these patient groups on overall ICU resource use. Methods: Secondary analysis of 69,862 patients in 17 ICUs in Finland, Estonia, and Switzerland in 2015–2017. Direct costs of care were allocated to patients using daily Therapeutic Intervention Scoring System (TISS) scores and ICU length of stay (LOS). The ratios of observed to severity-adjusted expected resource use (standardized resource use ratios; SRURs), direct costs and outcomes were assessed before and after excluding cardiac surgery or cardiac and neurosurgery. Results: Cardiac surgery and neurosurgery, performed only in university hospitals, represented 22% of all ICU admissions and 15–19% of direct costs. Cardiac surgery and neurosurgery were excluded with no consistent effect on SRURs in the whole cohort, regardless of cost separation method. Excluding cardiac surgery or cardiac surgery plus neurosurgery had highly variable effects on SRURs of individual university ICUs, whereas the non-university ICU SRURs decreased. Conclusions: Cardiac and neurosurgery have major effects on the cost structure of multidisciplinary ICUs. Extending SRUR analysis to patient subpopulations facilitates comparison of resource use between ICUs and may help to optimize resource allocation.Peer reviewe

Virtual reality stimulation to reduce the incidence of delirium in critically ill patients: study protocol for a randomized clinical trial.

BACKGROUND Delirium has been long considered as a major contributor to cognitive impairments and increased mortality following a critical illness. Pharmacologic and non-pharmacologic strategies are used against delirium in the intensive care unit (ICU), despite these strategies remaining controversial. Previous studies have shown the feasibility of using virtual reality within the ICU setting, and we propose to use this technology to investigate the effect of immersive virtual reality stimulation on the incidence of delirium in the ICU. Moreover, we propose to use motion sensors to determine if patient movement patterns can lead to early prediction of delirium onset. METHODS This study is conducted as a randomized clinical trial. A total of 920 critically ill patients in the ICU will participate. The control group will receive standard ICU care, whereas the intervention group will, in addition to the standard ICU care, receive relaxing 360-degree immersive virtual reality content played inside a head-mounted display with noise-cancelling headphones, three times a day. The first 100 patients, regardless of their group, will additionally have their movement patterns recorded using wearable and ambient sensors. Follow-up measurements will take place 6 months after discharge from the ICU. DISCUSSION Delirium is widely present within the ICU setting but lacks validated prevention and treatment strategies. By providing patients with virtual reality stimulation presented inside a head-mounted display and noise-cancelling headphones, participants may be isolated from disturbances on an ICU. It is believed that by doing so, the incidence of delirium will be decrease among these patients. Moreover, identifying movement patterns associated with delirium would allow for early detection and intervention, which may further improve long-term negative outcomes associated with delirium during critical care. TRIAL REGISTRATION ClinicalTrials.gov NCT04498585 . Registered on August 3, 2020

Variation in Severity-Adjusted Resource use and Outcome for Neurosurgical Emergencies in the Intensive Care Unit.

BACKGROUND The correlation between the standardized resource use ratio (SRUR) and standardized hospital mortality ratio (SMR) for neurosurgical emergencies is not known. We studied SRUR and SMR and the factors affecting these in patients with traumatic brain injury (TBI), nontraumatic intracerebral hemorrhage (ICH), and subarachnoid hemorrhage (SAH). METHODS We extracted data of patients treated in six university hospitals in three countries (2015-2017). Resource use was measured as SRUR based on purchasing power parity-adjusted direct costs and either intensive care unit (ICU) length of stay (costSRURlength of stay) or daily Therapeutic Intervention Scoring System scores (costSRURTherapeutic Intervention Scoring System). Five a priori defined variables reflecting differences in structure and organization between the ICUs were used as explanatory variables in bivariable models, separately for the included neurosurgical diseases. RESULTS Out of 28,363 emergency patients treated in six ICUs, 6,162 patients (22%) were admitted with a neurosurgical emergency (41% nontraumatic ICH, 23% SAH, 13% multitrauma TBI, and 23% isolated TBI). The mean costs for neurosurgical admissions were higher than for nonneurosurgical admissions, and the neurosurgical admissions corresponded to 23.6-26.0% of all direct costs related to ICU emergency admissions. A higher physician-to-bed ratio was associated with lower SMRs in the nonneurosurgical admissions but not in the neurosurgical admissions. In patients with nontraumatic ICH, lower costSRURs were associated with higher SMRs. In the bivariable models, independent organization of an ICU was associated with lower costSRURs in patients with nontraumatic ICH and isolated/multitrauma TBI but with higher SMRs in patients with nontraumatic ICH. A higher physician-to-bed ratio was associated with higher costSRURs for patients with SAH. Larger units had higher SMRs for patients with nontraumatic ICH and isolated TBI. None of the ICU-related factors were associated with costSRURs in nonneurosurgical emergency admissions. CONCLUSIONS Neurosurgical emergencies constitute a major proportion of all emergency ICU admissions. A lower SRUR was associated with higher SMR in patients with nontraumatic ICH but not for the other diagnoses. Different organizational and structural factors seemed to affect resource use for the neurosurgical patients compared with nonneurosurgical patients. This emphasizes the importance of case-mix adjustment when benchmarking resource use and outcomes