Symptomatic treatment of children with anti-NMDAR encephalitis.

Abstract AIM: We performed the first study on the perceived benefit and adverse effects of symptomatic management in children with anti-N-methyl-d-aspartate receptor (NMDAR) encephalitis. METHOD: A retrospective chart review was undertaken at two tertiary paediatric hospitals in Australia and New Zealand. We included 27 children (12 males, 15 females; mean age at admission 7y 1mo) with anti-NMDAR antibodies in serum or cerebrospinal fluid with a typical clinical syndrome. RESULTS: Only two out of 27 patients were white, whereas 16 out of 27 patients were from the Pacific Islands/New Zealand Maori. The mean duration of admission was 69 days (10-224d) and 48% of patients (13/27) needed treatment in an intensive care setting. A mean of eight medications per patient was used for symptomatic management. Symptoms treated were agitation (n=25), seizures (n=24), movement disorders (n=23), sleep disruption (n=17), psychiatric symptoms (n=10), and dysautonomia (n=four). The medications used included five different benzodiazepines (n=25), seven anticonvulsants (n=25), eight sedatives and sleep medications (n=23), five antipsychotics (n=12), and five medications for movement disorders (n=10). Sedative and sleep medications other than benzodiazepines were the most effective, with a mean benefit of 67.4% per medication and a mean adverse effect-benefit ratio of 0.04 per medication. Antipsychotic drugs were used for a short duration (median 9d), and had the poorest mean benefit per medication of 35.4% and an adverse effect-benefit ratio of 2.0 per medication. INTERPRETATION: Long-acting benzodiazepines, anticonvulsants, and clonidine can treat multiple symptoms. Patients with anti-NMDAR encephalitis appear vulnerable to antipsychotic-related adverse effects. Pacific Islanders appear to have a vulnerability to anti-NMDAR encephalitis in our region

The Reliability of Histamine Pharmacodynamic Response Phenotype Classification in Children With Allergic Disease.

We have identified distinct histamine pharmacodynamic response phenotypes in children with allergic disease utilizing histamine iontophoresis with laser Doppler (HILD). These response phenotypes may be relevant in guiding therapeutic decision making for agents targeting the allergic response pathways. However, the reliability of these response phenotypes has not been assessed. Therefore, we performed HILD in children with allergic rhinitis and/or asthma on two to three separate occasions. HILD response-time data were analyzed in NONMEM using a linked effect PKPD model. Examination of observed vs. classified response phenotypes predicted response plots and the sum of residuals. The intraclass correlation coefficient (ICC) was used to determine the reliability of phenotype classification. Eighty-two percent of children exhibited a reliable histamine response phenotype [intraclass correlation coefficient 0.77 (95% CI 0.44–0.93]. These preliminary results suggest moderate reliability of HILD response phenotype in children. Further exploration is needed to determine contributions to phenotype variability

Global transcript and phenotypic analysis of yeast cells expressing Ssa1, Ssa2, Ssa3 or Ssa4 as sole source of cytosolic Hsp70-Ssa chaperone activity.

BACKGROUND: Cytosolic Hsp70 is a ubiquitous molecular chaperone that is involved in responding to a variety of cellular stresses. A major function of Hsp70 is to prevent the aggregation of denatured proteins by binding to exposed hydrophobic regions and preventing the accumulation of amorphous aggregates. To gain further insight into the functional redundancy and specialisation of the highly homologous yeast Hsp70-Ssa family we expressed each of the individual Ssa proteins as the sole source of Hsp70 in the cell and assessed phenotypic differences in prion propagation and stress resistance. Additionally we also analysed the global gene expression patterns in yeast strains expressing individual Ssa proteins, using microarray and RT-qPCR analysis. RESULTS: We confirm and extend previous studies demonstrating that cells expressing different Hsp70-Ssa isoforms vary in their ability to propagate the yeast [PSI+] prion, with Ssa3 being the most proficient. Of the four Ssa family members the heat inducible isoforms are more proficient in acquiring thermotolerance and we show a greater requirement than was previously thought, for cellular processes in addition to the traditional Hsp104 protein disaggregase machinery, in acquiring such thermotolerance. Cells expressing different Hsp70-Ssa isoforms also display differences in phenotypic response to exposure to cell wall damaging and oxidative stress agents, again with the heat inducible isoforms providing better protection than constitutive isoforms. We assessed global transcriptome profiles for cells expressing individual Hsp70-Ssa isoforms as the sole source of cytosolic Hsp70, and identified a significant difference in cellular gene expression between these strains. Differences in gene expression profiles provide a rationale for some phenotypic differences we observed in this study. We also demonstrate a high degree of correlation between microarray data and RT-qPCR analysis for a selection of genes. CONCLUSIONS: The Hsp70-Ssa family provide both redundant and variant-specific functions within the yeast cell. Yeast cells expressing individual members of the Hsp70-Ssa family as the sole source of Ssa protein display differences in global gene expression profiles. These changes in global gene expression may contribute significantly to the phenotypic differences observed between the Hsp70-Ssa family members

Estimation of costs for control of Salmonella in high-risk feed materials and compound feed

Introduction: Feed is a potential and major source for introducing Salmonella into the animal-derived food chain. This is given special attention in the European Union (EU) efforts to minimize human food-borne Salmonella infections from animal-derived food. The objective of this study was to estimate the total extra cost for preventing Salmonella contamination of feed above those measures required to produce commercial feed according to EU regulation (EC) No 183/2005. The study was carried out in Sweden, a country where Salmonella infections in food-producing animals from feed have largely been eliminated. Methods: On the initiative and leadership of the competent authority, the different steps of feed production associated with control of Salmonella contamination were identified. Representatives for the major feed producers operating in the Swedish market then independently estimated the annual mean costs during the years 2009 and 2010. The feed producers had no known incentives to underestimate the costs. Results and discussion: The total cost for achieving a Salmonella-safe compound feed, when such a control is established, was estimated at 1.8–2.3 € per tonne of feed. Of that cost, 25% relates to the prevention of Salmonella contaminated high-risk vegetable feed materials (mainly soybean meal and rapeseed meal) from entering feed mills, and 75% for measures within the feed mills. Based on the feed formulations applied, those costs in relation to the farmers’ 2012 price for compound feed were almost equal for broilers and dairy cows (0.7%). Due to less use of protein concentrate to fatten pigs, the costs were lower (0.6%). These limited costs suggest that previous recommendations to enforce a Salmonella-negative policy for animal feed are realistic and economically feasible to prevent a dissemination of the pathogen to animal herds, their environment, and potentially to human food products

Mud-dominated basin margin progradation: processes and implications

The accretion of coarse-grained material at the shelf-edge rollover has been emphasized in studies of basin margin progradation, despite fine grained sediment (clay and silt) representing a volumetrically more significant component of subaqueous clinothems. The timing and processes of fine-grained sediment transport across the shelf and onto the slope remains an understudied facet of sedimentary basin stratigraphy. Three exhumed basin margin-scale clinothems of the Permian Waterford Formation, in the Karoo Basin, South Africa, offer outcrop examples of margin development through the accretion of mud during flooded shelf conditions. The progradation of wave/storm-influenced sandy shelf topset deposits over a thick mudstone succession and beyond a previously established sand-rich shelf-edge rollover suggests that some periods of basin margin progradation took place exclusively via dilute mud-rich gravity flows. Detailed outcrop and core study of offshore mudstones reveals a high content of organic debris and mica. Individual beds show normal and inverse grading, internal erosion surfaces and moderate to low bioturbation, reflecting relatively stressed conditions in frequently supplied outer shelf to upper slope regions. The estimated low gradient (<0.7º) of the Karoo Basin margin and prevailing wave/storm conditions facilitated prolonged suspension of fluid mud and transport across the shelf and beyond the shelf-edge rollover in sediment gravity flows. This study represents a rare example of mudstone-dominated shelf-edge rollover deposits documented at outcrop and core, and demonstrates how fine-grained sediment accretion can play a significant role in basin margin progradation. Conventional depositional models do not adequately account for progradation of basin margins in the absence of sand supply, which implies potential risks in the identification of shelf edge rollover positions and application of trajectory analysis in strongly progradational margins

Operations on windows and external doors in UK primary schools and their effects on indoor environmental quality

This study provides a comprehensive analysis of the predictors influencing operations on windows and external doors as well as their impact on IEQ, comfort and energy. The study was carried out in 31 naturally ventilated classrooms in eight primary schools in the UK during non-heating and heating seasons. The state of the windows and external doors was collected by time-lapse cameras and visual observations. Environmental variables impacting window operations were recorded at 10-min intervals. Correlational tests and predictive regression models were used to identify how windows open area (m2) were affected by environmental predictors. Results show that operative and outdoor temperature during the non-heating season and indoor and outdoor humidity during the heating season were the main predictors of windows open area (m2). The main driver for the operation of external doors was occupancy patterns, however, the period that they stayed open was dependent on temperature. The impact of windows and external doors' open area (m2) on operative temperature decreased after 40 min, however, its impact on CO2 level was only noticeable up to 30 min. Through opening more available windows, operative temperature (34% of the time) and CO2 levels (28% of the time) could be reduced during the non-heating season. Furthermore, energy waste could be avoided 67% of the time during the heating season by reducing the set-point temperature and training school occupants on when to operate windows. This study suggests several avenues to improve the impact of controls’ operation on IEQ, comfort and energy

Factors influencing the state of blinds and lights in primary schools: Behavioural models and opportunities to improve children's visual environment

The state of blinds and lights affects children's visual environment and comfort, however, there is a significant gap in research on the factors leading to the operation of blinds and lights in primary school classrooms. This study identifies and categorises the main drivers of operations on blinds and lights and investigates optimal light levels for children in primary schools. The study collected measurements of environmental variables, observations of operations on blinds and lights using forms and time-lapse cameras and visual sensation questionnaires in 31 naturally ventilated classrooms in the UK for one year. Results suggest that operations on blinds and lights are influenced by a range of contextual, occupant-related and building-related factors. Behavioural models of blind and light operation in primary schools are developed using the data collected. With regards to children's visual comfort, in the current study, at 730 lux, 80% of the children were satisfied with the light level in their classroom. The findings and models presented in this study could be used by designers of schools to achieve more visually comfortable classrooms. For example, the results suggest that vertical blinds rather than roller blinds may be a better design choice for classrooms as their slats can be adjusted to control direct sunlight but also allow ventilation. The research concludes with a range of strategies for managing the visual environment through operations on blinds to both reduce lighting energy consumption, as well as increase the quality of the visual environment thereby improving school children's health and productivity

Measurement of extravascular lung water to diagnose severe reperfusion lung injury following pulmonary endarterectomy: a prospective cohort clinical validation study

The measurement of extravascular lung water is a relatively new technology which has not yet been well validated as a clinically useful tool. We studied its utility in patients undergoing pulmonary endarterectomy as they frequently suffer reperfusion lung injury and associated oedematous lungs. Such patients are therefore ideal for evaluating this new monitor. We performed a prospective observational cohort study during which extravascular lung water index measurements were taken before and immediately after surgery and postoperatively in intensive care. Data were analysed for 57 patients; 21 patients (37%) experienced severe reperfusion lung injury. The first extravascular lung water index measurement after cardiopulmonary bypass failed to predict severe reperfusion lung injury, area under the receiver operating characteristic curve 0.59 (95%CI 0.44–0.74). On intensive care, extravascular lung water index correlated most strongly at 36 h, area under the receiver operating characteristic curve 0.90 (95%CI 0.80–1.00). Peri‐operative extravascular lung water index is not a useful measure to predict severe reperfusion lung injury after pulmonary endarterectomy, however, it does allow monitoring and measurement during the postoperative period. This study implies that extravascular lung water index can be used to directly assess pulmonary fluid overload and that monitoring patients by measuring extravascular lung water index during their intensive care stay is useful and correlates with their clinical course. This may allow directed, pre‐empted therapy to attenuate the effects and improve patient outcomes and should prompt further studies