Measurements of the E region neutral wind field

The neutral E-region wind field was measured at Calgary, Canada (51[deg]N, 114[deg]W) during 75 nights in 1982. Observations of the Doppler shift of the 5577-A emission line of atomic oxygen using a Fabry-Perot interferometer were converted to horizontal wind vectors. From the analysis of the data, four categories of wind characteristics were identified. In order of increasing magnetic activity these categories are (a) wind field mostly variable in space and time, (b) predominantly equatorward flow throughout the night, (c) predominantly poleward flow throughout the night and (d) north-westward flow before midnight and southward after midnight. The wind magnitude was also variable and on some disturbed days exceeded 200 m s-1.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/25723/1/0000280.pd

Comparisons between Canadian prairie MF radars, FPI (green and OH lines) and UARS HRDI systems

Detailed comparisons have been completed between the MF radars (MFR) in the Canadian prairies and three other systems: two ground-based Fabry-Perot interferometers (FPI) and the UARS high resolution Doppler imager (HRDI) system. The radars were at Sylvan Lake (52°N, 114°W), Robsart (49°N, 109°W) and the main continuing facility is at Saskatoon (52°N, 107°W). Statistical comparisons of hourly mean winds (1988–1992) for the Saskatoon MFR and FPI (557.7 nm green line) using scatter plots, wind speed-ratios, and direction-difference histograms show excellent agreement for Saskatoon. No serious biases in speeds or directions occur at the height of best agreement, 98 km. If anything, the MFR speeds appear bigger. The same applies to the Sylvan Lake MFR and Calgary FPI, where the best height is 88 km. In both cases these are close to the preferred heights for the emission layers. Differences between measurements seen on individual days are likely related to the influence of gravity waves (GW) upon the optical and radar systems, each of which have inherent spatial averaging (350, 50 km respectively), as well as the spatial difference between the nominal measurement locations. For HRDI, similar statistical comparisons are made, using single-overpass satellite winds and hourly means (to improve data quality) from MFR. Heights of best agreement, based upon direction-difference histograms, are shown; there is a tendency, beginning near 87 km, for these MFR heights to be 2 or 3 km greater than the HRDI heights. Speeds at these heights are typically larger for the satellite (MFR/HRDI = 0.7-0.8). Reasons for the differences are investigated. It is shown that the estimated errors and short-term (90 min) differences are larger for HRDI than for the MFR, indicating more noise or GW contamination. This leads to modest but significant differences in median speed-ratio (MFR/HRDI < 1). Also, comparison of the two systems is made under conditions when they agree best and when they show large disagreement. For the latter cases both systems show higher relative errors, and the HRDI vectors are frequently small. It is suggested that spatial or temporal GW wind fluctuations are the likely cause of the larger HRDI-MFR disagreement when wind speeds are small. No satisfactory explanation exists for the overall discrepancy is speeds between the MFR and HRDI.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/47858/1/585_1997_Article_70151099.pd

Non-alcoholic fatty liver disease, vascular inflammation and insulin resistance are exacerbated by TRAIL deletion in mice

Non-alcoholic fatty liver disease (NAFLD) incorporates steatosis, non-alcoholic steato-hepatitis (NASH) and liver cirrhosis, associating with diabetes and cardiovascular disease (CVD). TNF-related apoptosis-inducing ligand (TRAIL) is protective of CVD. We aimed to determine whether TRAIL protects against insulin resistance, NAFLD and vascular injury. Twelve-week high fat diet (HFD)-fed Trail -/- mice had increased plasma cholesterol, insulin and glucose compared to wildtype. Insulin tolerance was impaired with TRAIL-deletion, with reduced p-Akt, GLUT4 expression and glucose uptake in skeletal muscle. Hepatic triglyceride content, inflammation and fibrosis were increased with TRAIL-deletion, with elevated expression of genes regulating lipogenesis and gluconeogenesis. Moreover, Trail -/- mice exhibited reduced aortic vasorelaxation, impaired insulin signaling, and >20-fold increased mRNA expression for IL-1β, IL-6, and TNF-α. In vitro, palmitate treatment of hepatocytes increased lipid accumulation, inflammation and fibrosis, with TRAIL mRNA significantly reduced. TRAIL administration inhibited palmitate-induced hepatocyte lipid uptake. Finally, patients with NASH had significantly reduced plasma TRAIL compared to control, simple steatosis or obese individuals. These findings suggest that TRAIL protects against insulin resistance, NAFLD and vascular inflammation. Increasing TRAIL levels may be an attractive therapeutic strategy, to reduce features of diabetes, as well as liver and vascular injury, so commonly observed in individuals with NAFLD.Siân P. Cartland, Hanis H. Harith, Scott W. Genner, Lei Dang, Victoria C. Cogger, Melissa Vellozzi, Belinda A. Di Bartolo, Shane R. Thomas, Leon A. Adams, Mary M. Kavurm

Ponatinib (AP24534) inhibits MEKK3-KLF signaling and prevents formation and progression of cerebral cavernous malformations.

Cerebral cavernous malformation (CCM) is a common cerebrovascular disease that can occur sporadically or be inherited. They are major causes of stroke, cerebral hemorrhage, and neurological deficits in the younger population. Loss-of-function mutations in three genes, CCM1, CCM2, and CCM3, have been identified as the cause of human CCMs. Currently, no drug is available to treat CCM disease. Hyperactive mitogen-activated protein kinase kinase Kinase 3 (MEKK3) kinase signaling as a consequence of loss of CCM genes is an underlying cause of CCM lesion development. Using a U.S. Food and Drug Administration-approved kinase inhibitor library combined with virtual modeling and biochemical and cellular assays, we have identified a clinically approved small compound, ponatinib, that is capable of inhibiting MEKK3 activity and normalizing expression of downstream kruppel-like factor (KLF) target genes. Treatment with this compound in neonatal mouse models of CCM can prevent the formation of new CCM lesions and reduce the growth of already formed lesions. At the ultracellular level, ponatinib can normalize the flattening and disorganization of the endothelium caused by CCM deficiency. Collectively, our study demonstrates ponatinib as a novel compound that may prevent CCM initiation and progression in mouse models through inhibition of MEKK3-KLF signaling

Nosocomial or not? A combined epidemiological and genomic investigation to understand hospital-acquired COVID-19 infection on an elderly care ward.

BACKGROUND: COVID-19 has the potential to cause outbreaks in hospitals. Given the comorbid and elderly cohort of patients hospitalized, hospital-acquired COVID-19 infection is often fatal. Pathogen genome sequencing is becoming increasingly important in infection prevention and control (IPC). AIM: To inform the understanding of in-hospital SARS-CoV-2 transmission in order to improve IPC practices and to inform the future development of virological testing for IPC. METHODS: Patients detected COVID-19 positive by polymerase chain reaction on Ward A in April and May 2020 were included with contact tracing to identify other potential cases. Genome sequencing was undertaken for a subgroup of cases. Epidemiological, genomic, and cluster analyses were performed to describe the epidemiology and to identify factors contributing to the outbreak. FINDINGS: Fourteen cases were identified on Ward A. Contact tracing identified 16 further patient cases; in addition, eight healthcare workers (HCWs) were identified as being COVID-19 positive through a round of asymptomatic testing. Genome sequencing of 16 of these cases identified viral genomes differing by two single nucleotide polymorphisms or fewer, with further cluster analysis identifying two groups of infection (a five-person group and a six-person group). CONCLUSION: Despite the temporal relationship of cases, genome sequencing identified that not all cases shared transmission events. However, 11 samples were found to be closely related and these likely represented in-hospital transmission. This included three HCWs, thereby confirming transmission between patients and HCWs.S.R. and A.B. are part-funded from Research England’s Expanding Excellence in England (E3) Fund. The sequencing costs were funded by the COVID-19 Genomics UK (COG-UK) Consortium which is supported by funding from the Medical Research Council (MRC) part of UK Research & Innovation (UKRI), the National Institute for Health Research (NIHR) and Genome Research Limited, operating as the Wellcome Sanger Institute. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript

Study of user-experience of an objective test (QbTest) to aid ADHD assessment and medication management: a multi-methods approach

Background The diagnosis and monitoring of Attention deficit hyperactivity disorder (ADHD) typically relies on subjective reports and observations. Objective continuous performance tests (CPTs) have been incorporated into some services to support clinical decision making. However, the feasibility and acceptability of adding such a test into routine practice is unknown. The study aimed to investigate the feasibility and acceptability of adding an objective computerised test to the routine assessment and monitoring of attention deficit hyperactivity disorder (ADHD). Methods Semi-structured interviews were conducted with clinicians (n = 10) and families (parents/young people, n = 20) who participated in a randomised controlled trial. Additionally, the same clinicians (n = 10) and families (n = 76) completed a survey assessing their experience of the QbTest. The study took place in child and adolescent mental health and community paediatric clinics across the UK. Interview transcripts were thematically analysed. Results Interviewed clinicians and families valued the QbTest for providing an objective, valid assessment of symptoms. The QbTest was noted to facilitate communication between clinicians, families and schools. However, whereas clinicians were more unanimous on the usefulness of the QbTest, survey findings showed that, although the majority of families found the test useful, less than half felt the QbTest helped them understand the clinician’s decision making around diagnosis and medication. The QbTest was seen as a potentially valuable tool to use early in the assessment process to streamline the care pathway. Although clinicians were conscious of the additional costs, these could be offset by reductions in time to diagnosis and the delivery of the test by a Healthcare Assistant. Conclusions The findings indicate the QbTest is an acceptable and feasible tool to implement in routine clinical settings. Clinicians should be mindful to discuss the QbTest results with families to enable their understanding and engagement with the process. Further findings from definitive trials are required to understand the cost/benefit; however, the findings from this study support the feasibility and acceptability of integrating QbTest in the ADHD care pathway

TIMED Doppler Interferometer: Overview and recent results

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/94617/1/jgra18230.pd

Nosocomial or not? A combined epidemiological and genomic investigation to understand hospital-acquired COVID-19 infection on an elderly care ward

Background: COVID-19 has the potential to cause outbreaks in hospitals. Given the comorbid and elderly cohort of patients hospitalized, hospital-acquired COVID-19 infection is often fatal. Pathogen genome sequencing is becoming increasingly important in infection prevention and control (IPC). Aim: To inform the understanding of in-hospital SARS-CoV-2 transmission in order to improve IPC practices and to inform the future development of virological testing for IPC. Methods: Patients detected COVID-19 positive by polymerase chain reaction on Ward A in April and May 2020 were included with contact tracing to identify other potential cases. Genome sequencing was undertaken for a subgroup of cases. Epidemiological, genomic, and cluster analyses were performed to describe the epidemiology and to identify factors contributing to the outbreak. Findings: Fourteen cases were identified on Ward A. Contact tracing identified 16 further patient cases; in addition, eight healthcare workers (HCWs) were identified as being COVID-19 positive through a round of asymptomatic testing. Genome sequencing of 16 of these cases identified viral genomes differing by two single nucleotide polymorphisms or fewer, with further cluster analysis identifying two groups of infection (a five-person group and a six-person group). Conclusion: Despite the temporal relationship of cases, genome sequencing identified that not all cases shared transmission events. However, 11 samples were found to be closely related and these likely represented in-hospital transmission. This included three HCWs, thereby confirming transmission between patients and HCWs