Effect of Inhaled Xenon on Cerebral White Matter Damage in Comatose Survivors of Out-of-Hospital Cardiac Arrest: A Randomized Clinical Trial

IMPORTANCE: Evidence from preclinical models indicates that xenon gas can prevent the development of cerebral damage after acute global hypoxic-ischemic brain injury but, thus far, these putative neuroprotective properties have not been reported in human studies. OBJECTIVE: To determine the effect of inhaled xenon on ischemic white matter damage assessed with magnetic resonance imaging (MRI). DESIGN, SETTING, AND PARTICIPANTS: A randomized single-blind phase 2 clinical drug trial conducted between August 2009 and March 2015 at 2 multipurpose intensive care units in Finland. One hundred ten comatose patients (aged 24-76 years) who had experienced out-of-hospital cardiac arrest were randomized. INTERVENTIONS: Patients were randomly assigned to receive either inhaled xenon combined with hypothermia (33°C) for 24 hours (n = 55 in the xenon group) or hypothermia treatment alone (n = 55 in the control group). MAIN OUTCOMES AND MEASURES: The primary end point was cerebral white matter damage as evaluated by fractional anisotropy from diffusion tensor MRI scheduled to be performed between 36 and 52 hours after cardiac arrest. Secondary end points included neurological outcome assessed using the modified Rankin Scale (score 0 [no symptoms] through 6 [death]) and mortality at 6 months. RESULTS: Among the 110 randomized patients (mean age, 61.5 years; 80 men [72.7%]), all completed the study. There were MRI data from 97 patients (88.2%) a median of 53 hours (interquartile range [IQR], 47-64 hours) after cardiac arrest. The mean global fractional anisotropy values were 0.433 (SD, 0.028) in the xenon group and 0.419 (SD, 0.033) in the control group. The age-, sex-, and site-adjusted mean global fractional anisotropy value was 3.8% higher (95% CI, 1.1%-6.4%) in the xenon group (adjusted mean difference, 0.016 [95% CI, 0.005-0.027], P = .006). At 6 months, 75 patients (68.2%) were alive. Secondary end points at 6 months did not reveal statistically significant differences between the groups. In ordinal analysis of the modified Rankin Scale, the median (IQR) value was 1 (1-6) in the xenon group and 1 (0-6) in the control group (median difference, 0 [95% CI, 0-0]; P = .68). The 6-month mortality rate was 27.3% (15/55) in the xenon group and 34.5% (19/55) in the control group (adjusted hazard ratio, 0.49 [95% CI, 0.23-1.01]; P = .053). CONCLUSIONS AND RELEVANCE: Among comatose survivors of out-of-hospital cardiac arrest, inhaled xenon combined with hypothermia compared with hypothermia alone resulted in less white matter damage as measured by fractional anisotropy of diffusion tensor MRI. However, there was no statistically significant difference in neurological outcomes or mortality at 6 months. These preliminary findings require further evaluation in an adequately powered clinical trial designed to assess clinical outcomes associated with inhaled xenon among survivors of out-of-hospital cardiac arrest. TRIAL REGISTRATION: clinicaltrials.gov Identifier: NCT00879892

Healthy full-term infants' brain responses to emotionally and linguistically relevant sounds using a multi-feature mismatch negativity (MMN) paradigm

We evaluated the feasibility of a multi-feature mismatch negativity (MMN) paradigm in studying auditory processing of healthy newborns. The aim was to examine the automatic change-detection and processing of semantic and emotional information in speech in newborns. Brain responses of 202 healthy newborns were recorded with a multi-feature paradigm including a Finnish bi-syllabic pseudo-word/ta-ta/as a standard stimulus, six linguistically relevant deviant stimuli and three emotionally relevant stimuli (happy, sad, angry). Clear responses to emotional sounds were found already at the early latency window 100-200 ms, whereas responses to linguistically relevant minor changes and emotional stimuli at the later latency window 300-500 ms did not reach significance. Moreover, significant interaction between gender and emotional stimuli was found in the early latency window. Further studies on using multi-feature paradigms with linguistic and emotional stimuli in newborns are needed, especially those containing of follow-ups, enabling the assessment of the predictive value of early variations between subjects.Peer reviewe

Time to Rewrite the EU Directive on Combating Terrorism

The adoption of EU Directive 2017/541 on combating terrorism in March 2017 has profoundly changed the landscape of European counter-terrorism law. The primary aim of this Directive was to further harmonise the legal framework under which terrorist offences are prosecuted across EU Member States by establishing minimum rules and standards. However, the adverse consequences for the rule of law and human rights have been overlooked from the very outset by the EU institutions. Now, five years after its adoption, it is time for a thorough revision

Summary of the test prohibiting algorithmic discrimination

This document contains a test for digital discrimination based on disability. The academic article associated with this summary document demonstrates that this test can be incorporated into numerous international human rights law treaties through legal interpretation

Oral health promotion: the economic benefits to the NHS of increased use of sugarfree gum in the UK.

INTRODUCTION: The effect of sugarfree gum (SFG) on the prevention of dental caries has been established for some time. With increased constraints placed on healthcare budgets, the importance of economic considerations in decision-making about oral health interventions has increased. The aim of this study was to demonstrate the potential cost savings in dental care associated with increased levels of SFG usage. METHODS: The analysis examined the amount of money which would hypothetically be saved if the UK 12-year-old population chewed more SFG. The number of sticks chewed per year and the caries risk reduction were modelled to create a dose response curve. The costs of tooth restoration, tooth extraction in primary care settings and under general anaesthetic were considered, and the effects of caries reduction on these costs calculated. RESULTS: If all members of the UK 12-year-old population chewed SFG frequently (twice a day), the potential cost savings for the cohort over the course of one year were estimated to range from £1.2 to £3.3 million and if they chewed three times a day, £8.2 million could be saved each year. Sensitivity analyses of the key parameters demonstrated that cost savings would still be likely to be observed even in scenarios with less significant increases in SFG use. CONCLUSION: This study shows that if levels of SFG usage in the teenage population in the UK could be increased, substantial cost savings might be achieved

Soil aggregates as massively concurrent evolutionary incubators

Soil aggregation, a key component of soil structure, has mostly been examined from the perspective of soil management and the mediation of ecosystem processes such as soil carbon storage. However, soil aggregation is also a major factor to consider in terms of the fine-scale organization of the soil microbiome. For example, the physico-chemical conditions inside of aggregates usually differ from the conditions prevalent in the bulk soil and aggregates therefore increase the spatial heterogeneity of the soil. In addition, aggregates can provide a refuge for microbes against predation since their interior is not accessible to many predators. Soil aggregates are thus clearly important for microbial community ecology in soils (for example, Vos et al., 2013; Rillig et al., 2016) and for microbially driven biogeochemistry, and soil microbial ecologists are increasingly appreciating these aspects of soil aggregation. Soil aggregates have, however, so far been neglected when it comes to evolutionary considerations (Crawford et al., 2005) and we here propose that the process of soil aggregation should be considered as an important driver of evolution in the soil microbial community

DNA isolation protocol effects on nuclear DNA analysis by microarrays, droplet digital PCR, and whole genome sequencing, and on mitochondrial DNA copy number estimation.

Potential bias introduced during DNA isolation is inadequately explored, although it could have significant impact on downstream analysis. To investigate this in human brain, we isolated DNA from cerebellum and frontal cortex using spin columns under different conditions, and salting-out. We first analysed DNA using array CGH, which revealed a striking wave pattern suggesting primarily GC-rich cerebellar losses, even against matched frontal cortex DNA, with a similar pattern on a SNP array. The aCGH changes varied with the isolation protocol. Droplet digital PCR of two genes also showed protocol-dependent losses. Whole genome sequencing showed GC-dependent variation in coverage with spin column isolation from cerebellum. We also extracted and sequenced DNA from substantia nigra using salting-out and phenol / chloroform. The mtDNA copy number, assessed by reads mapping to the mitochondrial genome, was higher in substantia nigra when using phenol / chloroform. We thus provide evidence for significant method-dependent bias in DNA isolation from human brain, as reported in rat tissues. This may contribute to array "waves", and could affect copy number determination, particularly if mosaicism is being sought, and sequencing coverage. Variations in isolation protocol may also affect apparent mtDNA abundance

Genomic aberrations relate early and advanced stage ovarian cancer

Background Because of the distinct clinical presentation of early and advanced stage ovarian cancer, we aim to clarify whether these disease entities are solely separated by time of diagnosis or whether they arise from distinct molecular events. Methods Sixteen early and sixteen advanced stage ovarian carcinomas, matched for histological subtype and differentiation grade, were included. Genomic aberrations were compared for each early and advanced stage ovarian cancer by array comparative genomic hybridization. To study how the aberrations correlate to the clinical characteristics of the tumors we clustered tumors based on the genomic aberrations. Results The genomic aberration patterns in advanced stage cancer equalled those in early stage, but were more frequent in advanced stage (p=0.012). Unsupervised clustering based on genomic aberrations yielded two clusters that significantly discriminated early from advanced stage (p= 0.001), and that did differ significantly in survival (p= 0.002). These clusters however did give a more accurate prognosis than histological subtype or differentiation grade. Conclusion This study indicates that advanced stage ovarian cancer either progresses from early stage or from a common precursor lesion but that they do not arise from distinct carcinogenic molecular events. Furthermore, we show that array comparative genomic hybridization has the potential to identify clinically distinct patients

Intraoperative colonic pulse oximetry in left-sided colorectal surgery : can it predict anastomotic leak?

An anastomotic leak is a fairly common and a potentially lethal complication in colorectal surgery. Objective methods to assess the viability and blood circulation of the anastomosis could help in preventing leaks. Intraoperative pulse oximetry is a cheap, easy to use, fast, and readily available method to assess tissue viability. Our aim was to study whether intraoperative pulse oximetry can predict the development of an anastomotic leak. The study was a prospective single-arm study conducted between the years 2005 and 2011 in Helsinki University Hospital. Patient material consisted of 422 patients undergoing elective left-sided colorectal surgery. The patients were operated by one of the three surgeons. All of the operations were partial or total resections of the left side of the colon with a colorectal anastomosis. The intraoperative colonic oxygen saturation was measured with pulse oximetry from the colonic wall, and the values were analyzed with respect to post-operative complications. 2.3 times more operated anastomotic leaks occurred when the colonic StO(2) was Low intraoperative colonic StO(2) values are associated with the occurrence of anastomotic leak. Despite its handicaps, the method seems to be useful in assessing anastomotic viability.Peer reviewe