EEG recording latency in critically ill patients: Impact on outcome. An analysis of a randomized controlled trial (CERTA).

OBJECTIVE To assess, in adults with acute consciousness impairment, the impact of latency between hospital admission and EEG recording start, and their outcome. METHODS We reviewed data of the CERTA trial (NCT03129438) and explored correlations between EEG recording latency and mortality, Cerebral Performance Categories (CPC), and modified Rankin Scale (mRS) at 6 months, considering other variables, using uni- and multivariable analyses. RESULTS In univariable analysis of 364 adults, median latency between admission and EEG recordings was comparable between surviving (61.1 h; IQR: 24.3-137.7) and deceased patients (57.5 h; IQR: 22.3-141.1); p = 0.727. This did not change after adjusting for potential confounders, such as lower Glasgow Coma Score on enrolment (p < 0.001) and seizure or status epilepticus detection (p < 0.001). There was neither any correlation between EEG latency and mRS (rho 0.087, p 0.236), nor with CPC (rho = 0.027, p = 0.603). CONCLUSION This analysis shows no correlation between delays of EEG recordings and mortality or functional outcomes at 6 months in critically ill adults. SIGNIFICANCE These findings might suggest that in critically ill adults mortality correlates with underlying brain injury rather than EEG delay

The efficacy of antibiotics to prevent collibacilosis in broiler poultry: A protocol for a systematic review and network meta-analysis.

Antibiotics are used in broiler poultry production both for the prevention and treatment of infectious diseases. However, antibiotic use is a driver of antibiotic resistance. The World Health Organization has published numerous reports urging all stakeholders concerned with both food-producing animals and humans to establish recommended steps to enhance the prudent use of antimicrobials (WHO, 2015). Similarly, the World Animal Health Organization has also published recommendations and position statements regarding prudent use and risk management related to antimicrobial use in animals (OIE, 2017). Colibacillosis is an important bacterial pathogen of poultry, and a costly disease for the industry resulting in multimillion dollar losses annually through morbidity, mortality or carcass condemnation at slaughter. Colibacillosis refers to any localized or systemic infection caused entirely or partly by the organism avian pathogenic Escherichia coli (APEC). These bacteria may be isolated as the sole pathogen or contribute to a disease complex with mixed viral and bacterial infections (Guabirara and Schouler, 2015). Two main disease processes important in the broiler industry are early mortality and cellulitis. Early mortality is defined by chicks under a week of age experiencing a higher than normal percentage of deaths in a flock. Early mortality can be caused by many things, for example chilling, overheating, or dehydration, however E.coli infection, or colibacillosis, is one of the main culprits. Colibacillosis can present with omphalitis, yolk sacculitis, enteritis, pasty vents, pericarditis, perihepatitis, polyserositis, congested lungs, splenomegaly and darkened proventriculus or any these combinations (Guabiraba and Schouler, 2015; Geetha and Palanivel, 2018). Many chicks succumb to an early and severe infection or are culled due to excessive morbidity. Antibiotics are typically used to reduce early mortality (Chauvin et al., 2005; Dziva and Stevens, 2008). Those with severe infection are unlikely to survive, however appropriate treatment reduces transmission between birds and improves the suitability of those with a mild infection. Not every labelled drug for E.coli is efficacious, resistance is common (Kabir, 2010) and effectiveness can vary from flock to flock, even within a flock, with more than one strain and more than one treatment. Understanding the efficacy of antibiotics used to prevent colibacillosis in broiler chickens is essential to optimizing their use; ineffective antibiotics should not be used for prevention or, if there are multiple efficacious antibiotics, their importance to human medicine should be considered when making decisions on antibiotic use. Systematic reviews of randomized controlled trials, and network meta-analysis to provide input on relative antibiotic efficacy, will yield the highest level of evidence for efficacy of treatments under field conditions (Sargeant and O’Connor, 2014)

The efficacy of antibiotics to control colibacillosis in broiler poultry: a systematic review

The objective of this systematic review was to evaluate the efficacy of antibiotics to prevent or control colibacillosis in broilers. Studies found eligible were conducted controlled trials in broilers that evaluated an antibiotic intervention, with at least one of the following outcomes: mortality, feed conversion ratio (FCR), condemnations at slaughter, or total antibiotic use. Four electronic databases plus the gray literature were searched. Abstracts were screened for eligibility and data were extracted from eligible trials. Risk of bias was evaluated. Seven trials reported eligible outcomes in a format that allowed data extraction; all reported results for FCR and one also reported mortality. Due to the heterogeneity in the interventions and outcomes evaluated, it was not feasible to conduct meta-analysis. Qualitatively, for FCR, comparisons between an antibiotic and an alternative product did not show a significant benefit for either. Some of the comparisons between an antibiotic and a no-treatment placebo showed a numerical benefit to antibiotics, but with wide confidence intervals. The risk-of-bias assessment revealed concerns with reporting of key trial features. The results of this review do not provide compelling evidence for or against the efficacy of antibiotics for the control of colibacillosis

Biorefining of wheat straw:accounting for the distribution of mineral elements in pretreated biomass by an extended pretreatment–severity equation

BACKGROUND: Mineral elements present in lignocellulosic biomass feedstocks may accumulate in biorefinery process streams and cause technological problems, or alternatively can be reaped for value addition. A better understanding of the distribution of minerals in biomass in response to pretreatment factors is therefore important in relation to development of new biorefinery processes. The objective of the present study was to examine the levels of mineral elements in pretreated wheat straw in response to systematic variations in the hydrothermal pretreatment parameters (pH, temperature, and treatment time), and to assess whether it is possible to model mineral levels in the pretreated fiber fraction. RESULTS: Principal component analysis of the wheat straw biomass constituents, including mineral elements, showed that the recovered levels of wheat straw constituents after different hydrothermal pretreatments could be divided into two groups: 1) Phosphorus, magnesium, potassium, manganese, zinc, and calcium correlated with xylose and arabinose (that is, hemicellulose), and levels of these constituents present in the fiber fraction after pretreatment varied depending on the pretreatment-severity; and 2) Silicon, iron, copper, aluminum correlated with lignin and cellulose levels, but the levels of these constituents showed no severity-dependent trends. For the first group, an expanded pretreatment-severity equation, containing a specific factor for each constituent, accounting for variability due to pretreatment pH, was developed. Using this equation, the mineral levels could be predicted with R(2) > 0.75; for some with R(2) up to 0.96. CONCLUSION: Pretreatment conditions, especially pH, significantly influenced the levels of phosphorus, magnesium, potassium, manganese, zinc, and calcium in the resulting fiber fractions. A new expanded pretreatment-severity equation is proposed to model and predict mineral composition in pretreated wheat straw biomass

Faulty cardiac repolarization reserve in alternating hemiplegia of childhood broadens the phenotype

Alternating hemiplegia of childhood is a rare disorder caused by de novo mutations in the ATP1A3 gene, expressed in neurons and cardiomyocytes. As affected individuals may survive into adulthood, we use the term 'alternating hemiplegia'. The disorder is characterized by early-onset, recurrent, often alternating, hemiplegic episodes; seizures and non-paroxysmal neurological features also occur. Dysautonomia may occur during hemiplegia or in isolation. Premature mortality can occur in this patient group and is not fully explained. Preventable cardiorespiratory arrest from underlying cardiac dysrhythmia may be a cause. We analysed ECG recordings of 52 patients with alternating hemiplegia from nine countries: all had whole-exome, whole-genome, or direct Sanger sequencing of ATP1A3. Data on autonomic dysfunction, cardiac symptoms, medication, and family history of cardiac disease or sudden death were collected. All had 12-lead electrocardiogram recordings available for cardiac axis, cardiac interval, repolarization pattern, and J-point analysis. Where available, historical and prolonged single-lead electrocardiogram recordings during electrocardiogram-videotelemetry were analysed. Half the cohort (26/52) had resting 12-lead electrocardiogram abnormalities: 25/26 had repolarization (T wave) abnormalities. These abnormalities were significantly more common in people with alternating hemiplegia than in an age-matched disease control group of 52 people with epilepsy. The average corrected QT interval was significantly shorter in people with alternating hemiplegia than in the disease control group. J wave or J-point changes were seen in six people with alternating hemiplegia. Over half the affected cohort (28/52) had intraventricular conduction delay, or incomplete right bundle branch block, a much higher proportion than in the normal population or disease control cohort (P = 0.0164). Abnormalities in alternating hemiplegia were more common in those ≥16 years old, compared with those <16 (P = 0.0095), even with a specific mutation (p.D801N; P = 0.045). Dynamic, beat-to-beat or electrocardiogram-to-electrocardiogram, changes were noted, suggesting the prevalence of abnormalities was underestimated. Electrocardiogram changes occurred independently of seizures or plegic episodes. Electrocardiogram abnormalities are common in alternating hemiplegia, have characteristics reflecting those of inherited cardiac channelopathies and most likely amount to impaired repolarization reserve. The dynamic electrocardiogram and neurological features point to periodic systemic decompensation in ATP1A3-expressing organs. Cardiac dysfunction may account for some of the unexplained premature mortality of alternating hemiplegia. Systematic cardiac investigation is warranted in alternating hemiplegia of childhood, as cardiac arrhythmic morbidity and mortality are potentially preventable

The Association between Intrauterine Inflammation and Spontaneous Vaginal Delivery at Term: A Cross-Sectional Study

BACKGROUND:Different factors contribute to the onset of labor at term. In animal models onset of labor is characterized by an inflammatory response. The role of intrauterine inflammation, although implicated in preterm birth, is not yet established in human term labor. We hypothesized that intrauterine inflammation at term is associated with spontaneous onset of labor. METHODS/RESULTS:In two large urban hospitals in the Netherlands, a cross-sectional study of spontaneous onset term vaginal deliveries and elective caesarean sections (CS), without signs of labor, was carried out. Placentas and amniotic fluid samples were collected during labor and/or at delivery. Histological signs of placenta inflammation were determined. Amniotic fluid proinflammatory cytokine concentrations were measured using ELISA. A total of 375 women were included. In term vaginal deliveries, more signs of intrauterine inflammation were found than in elective CS: the prevalence of chorioamnionitis was higher (18 vs 4%, p = 0.02) and amniotic fluid concentration of IL-6 was higher (3.1 vs 0.37 ng/mL, p<0.001). Similar results were obtained for IL-8 (10.93 vs 0.96 ng/mL, p<0.001) and percentage of detectable TNF-alpha (50 vs 4%, p<0.001). CONCLUSIONS:This large cross-sectional study shows that spontaneous term delivery is characterized by histopathological signs of placenta inflammation and increased amniotic fluid proinflammatory cytokines

Epilepsy, hippocampal sclerosis and febrile seizures linked by common genetic variation around SCN1A

Epilepsy comprises several syndromes, amongst the most common being mesial temporal lobe epilepsy with hippocampal sclerosis. Seizures in mesial temporal lobe epilepsy with hippocampal sclerosis are typically drug-resistant, and mesial temporal lobe epilepsy with hippocampal sclerosis is frequently associated with important co-morbidities, mandating the search for better understanding and treatment. The cause of mesial temporal lobe epilepsy with hippocampal sclerosis is unknown, but there is an association with childhood febrile seizures. Several rarer epilepsies featuring febrile seizures are caused by mutations in SCN1A, which encodes a brain-expressed sodium channel subunit targeted by many anti-epileptic drugs. We undertook a genome-wide association study in 1018 people with mesial temporal lobe epilepsy with hippocampal sclerosis and 7552 control subjects, with validation in an independent sample set comprising 959 people with mesial temporal lobe epilepsy with hippocampal sclerosis and 3591 control subjects. To dissect out variants related to a history of febrile seizures, we tested cases with mesial temporal lobe epilepsy with hippocampal sclerosis with (overall n = 757) and without (overall n = 803) a history of febrile seizures. Meta-analysis revealed a genome-wide significant association for mesial temporal lobe epilepsy with hippocampal sclerosis with febrile seizures at the sodium channel gene cluster on chromosome 2q24.3 [rs7587026, within an intron of the SCN1A gene, P = 3.36 × 10−9, odds ratio (A) = 1.42, 95% confidence interval: 1.26-1.59]. In a cohort of 172 individuals with febrile seizures, who did not develop epilepsy during prospective follow-up to age 13 years, and 6456 controls, no association was found for rs7587026 and febrile seizures. These findings suggest SCN1A involvement in a common epilepsy syndrome, give new direction to biological understanding of mesial temporal lobe epilepsy with hippocampal sclerosis with febrile seizures, and open avenues for investigation of prognostic factors and possible prevention of epilepsy in some children with febrile seizure

Atypical face shape and genomic structural variants in epilepsy

Many pathogenic structural variants of the human genome are known to cause facial dysmorphism. During the past decade, pathogenic structural variants have also been found to be an important class of genetic risk factor for epilepsy. In other fields, face shape has been assessed objectively using 3D stereophotogrammetry and dense surface models. We hypothesized that computer-based analysis of 3D face images would detect subtle facial abnormality in people with epilepsy who carry pathogenic structural variants as determined by chromosome microarray. In 118 children and adults attending three European epilepsy clinics, we used an objective measure called Face Shape Difference to show that those with pathogenic structural variants have a significantly more atypical face shape than those without such variants. This is true when analysing the whole face, or the periorbital region or the perinasal region alone. We then tested the predictive accuracy of our measure in a second group of 63 patients. Using a minimum threshold to detect face shape abnormalities with pathogenic structural variants, we found high sensitivity (4/5, 80% for whole face; 3/5, 60% for periorbital and perinasal regions) and specificity (45/58, 78% for whole face and perinasal regions; 40/58, 69% for periorbital region). We show that the results do not seem to be affected by facial injury, facial expression, intellectual disability, drug history or demographic differences. Finally, we use bioinformatics tools to explore relationships between facial shape and gene expression within the developing forebrain. Stereophotogrammetry and dense surface models are powerful, objective, non-contact methods of detecting relevant face shape abnormalities. We demonstrate that they are useful in identifying atypical face shape in adults or children with structural variants, and they may give insights into the molecular genetics of facial development

Collins and Sivers asymmetries in muonproduction of pions and kaons off transversely polarised protons

Measurements of the Collins and Sivers asymmetries for charged pions and charged and neutral kaons produced in semi-inclusive deep-inelastic scattering of high energy muons off transversely polarised protons are presented. The results were obtained using all the available COMPASS proton data, which were taken in the years 2007 and 2010. The Collins asymmetries exhibit in the valence region a non-zero signal for pions and there are hints of non-zero signal also for kaons. The Sivers asymmetries are found to be positive for positive pions and kaons and compatible with zero otherwise. © 2015