Space station structural dynamics/reaction control system interaction study

The performance of the Reaction Control System is impacted by the extreme flexibility of the space station structure. The method used to analyze the periodic thrust profile of a simple form of phase plane logic is presented. The results illustrate the effect on flexible body response of the type of phase plane logic utilized and the choice of control parameters: cycle period and attitude deadband

Characterisation of neonatal seizures and their treatment using continuous EEG monitoring: a multicentre experience.

OBJECTIVE: The aim of this multicentre study was to describe detailed characteristics of electrographic seizures in a cohort of neonates monitored with multichannel continuous electroencephalography (cEEG) in 6 European centres. METHODS: Neonates of at least 36 weeks of gestation who required cEEG monitoring for clinical concerns were eligible, and were enrolled prospectively over 2 years from June 2013. Additional retrospective data were available from two centres for January 2011 to February 2014. Clinical data and EEGs were reviewed by expert neurophysiologists through a central server. RESULTS: Of 214 neonates who had recordings suitable for analysis, EEG seizures were confirmed in 75 (35%). The most common cause was hypoxic-ischaemic encephalopathy (44/75, 59%), followed by metabolic/genetic disorders (16/75, 21%) and stroke (10/75, 13%). The median number of seizures was 24 (IQR 9-51), and the median maximum hourly seizure burden in minutes per hour (MSB) was 21 min (IQR 11-32), with 21 (28%) having status epilepticus defined as MSB>30 min/hour. MSB developed later in neonates with a metabolic/genetic disorder. Over half (112/214, 52%) of the neonates were given at least one antiepileptic drug (AED) and both overtreatment and undertreatment was evident. When EEG monitoring was ongoing, 27 neonates (19%) with no electrographic seizures received AEDs. Fourteen neonates (19%) who did have electrographic seizures during cEEG monitoring did not receive an AED. CONCLUSIONS: Our results show that even with access to cEEG monitoring, neonatal seizures are frequent, difficult to recognise and difficult to treat. OBERSERVATION STUDY NUMBER: NCT02160171

Hepatic Stearoyl-CoA Desaturase (SCD)-1 Activity and Diacylglycerol but Not Ceramide Concentrations Are Increased in the Nonalcoholic Human Fatty Liver

OBJECTIVE—To determine whether 1) hepatic ceramide and diacylglycerol concentrations, 2) SCD1 activity, and 3) hepatic lipogenic index are increased in the human nonalcoholic fatty liver

CAF01 Potentiates Immune Responses and Efficacy of an Inactivated Influenza Vaccine in Ferrets

Trivalent inactivated vaccines (TIV) against influenza are given to 350 million people every year. Most of these are non-adjuvanted vaccines whose immunogenicity and protective efficacy are considered suboptimal. Commercially available non-adjuvanted TIV are known to elicit mainly a humoral immune response, whereas the induction of cell-mediated immune responses is negligible. Recently, a cationic liposomal adjuvant (dimethyldioctadecylammonium/trehalose 6,6′-dibehenate, CAF01) was developed. CAF01 has proven to enhance both humoral and cell-mediated immune responses to a number of different experimental vaccine candidates. In this study, we compared the immune responses in ferrets to a commercially available TIV with the responses to the same vaccine mixed with the CAF01 adjuvant. Two recently circulating H1N1 viruses were used as challenge to test the vaccine efficacy. CAF01 improved the immunogenicity of the vaccine, with increased influenza-specific IgA and IgG levels. Additionally, CAF01 promoted cellular-mediated immunity as indicated by interferon-gamma expressing lymphocytes, measured by flow cytometry. CAF01 also enhanced the protection conferred by the vaccine by reducing the viral load measured in nasal washes by RT-PCR. Finally, CAF01 allowed for dose-reduction and led to higher levels of protection compared to TIV adjuvanted with a squalene emulsion. The data obtained in this human-relevant challenge model supports the potential of CAF01 in future influenza vaccines

Susceptibility of Pancreatic Beta Cells to Fatty Acids Is Regulated by LXR/PPARα-Dependent Stearoyl-Coenzyme A Desaturase

Chronically elevated levels of fatty acids-FA can cause beta cell death in vitro. Beta cells vary in their individual susceptibility to FA-toxicity. Rat beta cells were previously shown to better resist FA-toxicity in conditions that increased triglyceride formation or mitochondrial and peroxisomal FA-oxidation, possibly reducing cytoplasmic levels of toxic FA-moieties. We now show that stearoyl-CoA desaturase-SCD is involved in this cytoprotective mechanism through its ability to transfer saturated FA into monounsaturated FA that are incorporated in lipids. In purified beta cells, SCD expression was induced by LXR- and PPARα-agonists, which were found to protect rat, mouse and human beta cells against palmitate toxicity. When their SCD was inhibited or silenced, the agonist-induced protection was also suppressed. A correlation between beta cell-SCD expression and susceptibility to palmitate was also found in beta cell preparations isolated from different rodent models. In mice with LXR-deletion (LXRβ-/- and LXRαβ-/-), beta cells presented a reduced SCD-expression as well as an increased susceptibility to palmitate-toxicity, which could not be counteracted by LXR or PPARα agonists. In Zucker fatty rats and in rats treated with the LXR-agonist TO1317, beta cells show an increased SCD-expression and lower palmitate-toxicity. In the normal rat beta cell population, the subpopulation with lower metabolic responsiveness to glucose exhibits a lower SCD1 expression and a higher susceptibility to palmitate toxicity. These data demonstrate that the beta cell susceptibility to saturated fatty acids can be reduced by stearoyl-coA desaturase, which upon stimulation by LXR and PPARα agonists favors their desaturation and subsequent incorporation in neutral lipids

Stearoyl CoA desaturase 1 is elevated in obesity but protects against fatty acid-induced skeletal muscle insulin resistance in vitro

AIMS/HYPOTHESIS: Stearoyl CoA desaturase 1 (SCD1) is implicated in mediating obesity and insulin resistance. Paradoxically, SCD1 converts saturated fatty acids, the lipid species implicated in mediating insulin resistance, to monounsaturated fatty acids. The aim of the present study was to assess the molecular mechanisms that implicate SCD1 in the aetiology of fatty acid-induced insulin resistance. METHODS: SCD1 protein was transiently decreased or increased in rat L6 skeletal muscle myotubes using SCD1 short interfering RNA (siRNA) or liposome-mediated transfection of pcDNA3.1/Hygro-mSCD1, respectively. RESULTS: Reducing SCD1 protein resulted in marked esterification of exogenous fatty acids into diacylglycerol (DAG) and ceramide. Insulin-stimulated Akt activity and phosphorylation and 2-deoxyglucose uptake were reduced with SCD1 siRNA. Exposure of L6 myotubes to palmitate abolished insulin-stimulated glucose uptake in both control and SCD1 siRNA myotubes. Overexpression of SCD1 resulted in triacylglycerol esterification but attenuated ceramide and DAG accumulation and protected myotubes from fatty acid-induced insulin resistance. CONCLUSIONS/INTERPRETATION: SCD1 protects from cellular toxicity in L6 myotubes by preventing excessive accumulation of bioactive lipid metabolites

Extranasal S aureus colonization predisposes to bloodstream infections in patients on hemodialysis with non-cuffed internal jugular vein catheters

Background: Staphylococcal infection of endogenous origin is an important cause of morbidity and mortality in patients who receive hemodialysis (HD). The risk of such infections in nasal carriers of the organism is well defined. Extranasal carriage of the organism at extranasalsites may pose similar risks. Design: Prospective observational study. Setting and Participants: A total of seventy patients about to undergo internal jugular vein catheterization for HD were enrolled. Swab cultures were obtained from anterior nares, posterior pharynx, axillae, toe toe web spaces and vascular access sites at baseline and one week later. A patient was defined as a persistent carrier when the same organism was grown in both samples. Outcomes: S. aureusbloodstream infections as assessed by blood and catheter tip cultures over a 90 day period. Measurement: Number of catheter related bloodstream infections amongst different subgroups using parameteric and non-parameteric tests. Results: The mean age of the patients was 43.71±16.2 years. Persistent S. aureus carriage at anterior nares, throat, axilla, toe web spaces, vascular access site and all sites was documented in 27.9%, 11.4%,40%,32.9%,4.3% and 64.2% of patients respectively. Fifteen patients developed S. aureus related infections. Catheter related S. aureus infections (CRI) were more likely in persistent carriers than non persistent carriers with odds ratios (95% CI) of 10.2 (2.8-37.1), 8.6 (1.7-42.2), 17.3 (3.4-86.0), 3.0 (0.9-9.8) and 1.9 (0.2-22.4) foranterior nares, throat, axilla, toe web spaces andvascular access site carriers respectively. The probability of developing CRI in persistent S. aureus carriers was 55% compared to none in non carriers at 90 days (p=0.04). Limitations: Small number of subjects, lack of molecular phenotyping. Conclusion: ExtranasalS aureuscarriage is as significant a risk factor as nasal carriage for staphylococcal infections in patients on HD through catheters

Extranasal S aureus colonization predisposes to bloodstream infections in patients on hemodialysis with non-cuffed internal jugular vein catheters

Background: Staphylococcal infection of endogenous origin is an important cause of morbidity and mortality in patients who receive hemodialysis (HD). The risk of such infections in nasal carriers of the organism is well defined. Extranasal carriage of the organism at extranasalsites may pose similar risks. Design: Prospective observational study. Setting and Participants: A total of seventy patients about to undergo internal jugular vein catheterization for HD were enrolled. Swab cultures were obtained from anterior nares, posterior pharynx, axillae, toe toe web spaces and vascular access sites at baseline and one week later. A patient was defined as a persistent carrier when the same organism was grown in both samples. Outcomes: S. aureusbloodstream infections as assessed by blood and catheter tip cultures over a 90 day period. Measurement: Number of catheter related bloodstream infections amongst different subgroups using parameteric and non-parameteric tests. Results: The mean age of the patients was 43.71±16.2 years. Persistent S. aureus carriage at anterior nares, throat, axilla, toe web spaces, vascular access site and all sites was documented in 27.9%, 11.4%,40%,32.9%,4.3% and 64.2% of patients respectively. Fifteen patients developed S. aureus related infections. Catheter related S. aureus infections (CRI) were more likely in persistent carriers than non persistent carriers with odds ratios (95% CI) of 10.2 (2.8-37.1), 8.6 (1.7-42.2), 17.3 (3.4-86.0), 3.0 (0.9-9.8) and 1.9 (0.2-22.4) foranterior nares, throat, axilla, toe web spaces andvascular access site carriers respectively. The probability of developing CRI in persistent S. aureus carriers was 55% compared to none in non carriers at 90 days (p=0.04). Limitations: Small number of subjects, lack of molecular phenotyping. Conclusion: ExtranasalS aureuscarriage is as significant a risk factor as nasal carriage for staphylococcal infections in patients on HD through catheters