Effect of opening ratios with and without louvers in cross ventilation using CFD

As the world marches forward implementing concepts of sustainable buildings, higher reliance on natural ventilation can be obtained through louvers. In this research of cross ventilation in a generic isolated building, the leeward opening sizes were manipulated to 1:1, 1:0.25 and 1:0.5, with louver angles of 0°, 15°, 30°, 45° and no louvers. An Atmospheric Boundary Layer (ABL) condition was applied at the inlet of the flow domain and a 3D-steady Reynolds-Averaged Navier–Stokes (RANS) equation was solved with the Shear Stress Transport (SST) k-ω turbulence model. Mesh sensitivity analysis and model validation were performed as per best practices. The results show that as the size of the leeward opening decreases, the acceleration through the louver blades increases. In the absence and presence of louvers, as the windward-louver (W-L) ratio increased from 1:0.25 to 1:1, its dimensionless flow rate (DFR) increases. Highest DFR was obtained when the W-L ratio was 1:1 and the louver angle was 0°, second to louver angle of 15°, followed by the configuration without louvers present. Their respective DFR values were 0.588, 0.544 and 0.522. As the louver angle increased from 0° to 45°, the DFR reduced for all opening W-L ratios

Endovascular therapy after stroke in a patient treated with dabigatran

Andrew W Moey, Simon A Koblar, Steve Chryssidis, Martin Robinson and Jim Janne

Reinitiation of mRNA translation in a patient with X-linked infantile spasms with a protein-truncating variant in ARX

Mutations in the Aristaless-related homeobox gene (ARX) lead to a range of X-linked intellectual disability phenotypes, with truncating variants generally resulting in severe X-linked lissencephaly with ambiguous genitalia (XLAG), and polyalanine expansions and missense variants resulting in infantile spasms. We report two male patients with early-onset infantile spasms in whom a novel c.34G>T (p.(E12*)) variant was identified in the ARX gene. A similar variant c.81C>G (p.(Y27*)), has previously been described in two affected cousins with early-onset infantile spasms, leading to reinitiation of ARX mRNA translation resulting in an N-terminal truncated protein. We show that the novel c.34G>T (p.(E12*)) variant also reinitiated mRNA translation at the next AUG codon (c.121-123 (p.M41)), producing the same N-terminally truncated protein. The production of both of these truncated proteins was demonstrated to be at markedly reduced levels using in vitro cell assays. Using luciferase reporter assays, we demonstrate that transcriptional repression capacity of ARX was diminished by both the loss of the N-terminal corepressor octapeptide domain, as a consequence of truncation, and the marked reduction in mutant protein expression. Our study indicates that premature termination mutations very early in ARX lead to reinitiation of translation to produce N-terminally truncated protein at markedly reduced levels of expression. We conclude that even low levels of N-terminally truncated ARX is sufficient to improve the patient's phenotype compared with the severe phenotype of XLAG that includes malformations of the brain and genitalia normally seen in complete loss-of-function mutations in ARX.Ching Moey, Scott Topper, Mary Karn, Amy Knight Johnson, Soma Das, Jorge Vidaurre and Cheryl Shoubridg

An emerging female phenotype with loss-of-function mutations in the Aristaless-related homeodomain transcription factor ARX

The devastating clinical presentation of X-linked lissencephaly with abnormal genitalia (XLAG) is invariably caused by loss-of-function mutations in the Aristaless-related homeobox (ARX) gene. Mutations in this X-chromosome gene contribute to intellectual disability (ID) with co-morbidities including seizures and movement disorders such as dystonia in affected males. The detection of affected females with mutations in ARX is increasing. We present a family with multiple affected individuals, including two females. Two male siblings presenting with XLAG were deceased prior to full-term gestation or within the first few weeks of life. Of the two female siblings, one presented with behavioral disturbances, mild ID, a seizure disorder, and complete agenesis of the corpus callosum (ACC), similar to the mother's phenotype. A novel insertion mutation in Exon 2 of ARX was identified, c.982delCinsTTT predicted to cause a frameshift at p.(Q328Ffs* 37). Our finding is consistent with loss-of-function mutations in ARX causing XLAG in hemizygous males and extends the findings of ID and seizures in heterozygous females. We review the reported phenotypes of females with mutations in ARX and highlight the importance of screening ARX in male and female patients with ID, seizures, and in particular with complete ACC.Tessa Mattiske, Ching Moey, Lisenka E. Vissers, Natalie Thorne, Peter Georgeson, Madhura Bakshi and Cheryl Shoubridg

Assessment of willingness to Tele-monitoring interventions in patients with type 2 diabetes and/or hypertension in the public primary healthcare setting

10.1186/s12911-020-1024-4BMC Medical Informatics and Decision Making2011

Lancet Oncol

BACKGROUND: Immune checkpoint inhibitors (ICIs) have substantially improved clinical outcomes in multiple cancer types and are increasingly being used in early disease settings and in combinations of different immunotherapies. However, ICIs can also cause severe or fatal immune-related adverse-events (irAEs). We aimed to identify and characterise cardiovascular irAEs that are significantly associated with ICIs. METHODS: In this observational, retrospective, pharmacovigilance study, we used VigiBase, WHO's global database of individual case safety reports, to compare cardiovascular adverse event reporting in patients who received ICIs (ICI subgroup) with this reporting in the full database. This study included all cardiovascular irAEs classified by group queries according to the Medical Dictionary for Regulatory Activities, between inception on Nov 14, 1967, and Jan 2, 2018. We evaluated the association between ICIs and cardiovascular adverse events using the reporting odds ratio (ROR) and the information component (IC). IC is an indicator value for disproportionate Bayesian reporting that compares observed and expected values to find associations between drugs and adverse events. IC025 is the lower end of the IC 95% credibility interval, and an IC025 value of more than zero is deemed significant. This study is registered with ClinicalTrials.gov, number NCT03387540. FINDINGS: We identified 31 321 adverse events reported in patients who received ICIs and 16 343 451 adverse events reported in patients treated with any drugs (full database) in VigiBase. Compared with the full database, ICI treatment was associated with higher reporting of myocarditis (5515 reports for the full database vs 122 for ICIs, ROR 11.21 [95% CI 9.36-13.43]; IC025 3.20), pericardial diseases (12 800 vs 95, 3.80 [3.08-4.62]; IC025 1.63), and vasculitis (33 289 vs 82, 1.56 [1.25-1.94]; IC025 0.03), including temporal arteritis (696 vs 18, 12.99 [8.12-20.77]; IC025 2.59) and polymyalgia rheumatica (1709 vs 16, 5.13 [3.13-8.40]; IC025 1.33). Pericardial diseases were reported more often in patients with lung cancer (49 [56%] of 87 patients), whereas myocarditis (42 [41%] of 103 patients) and vasculitis (42 [60%] of 70 patients) were more commonly reported in patients with melanoma (chi(2) test for overall subgroup comparison, p80%), with death occurring in 61 (50%) of 122 myocarditis cases, 20 (21%) of 95 pericardial disease cases, and five (6%) of 82 vasculitis cases (chi(2) test for overall comparison between pericardial diseases, myocarditis, and vasculitis, p<0.0001). INTERPRETATION: Treatment with ICIs can lead to severe and disabling inflammatory cardiovascular irAEs soon after commencement of therapy. In addition to life-threatening myocarditis, these toxicities include pericardial diseases and temporal arteritis with a risk of blindness. These events should be considered in patient care and in combination clinical trial designs (ie, combinations of different immunotherapies as well as immunotherapies and chemotherapy). FUNDING: The Cancer Institut Thematique Multi-Organisme of the French National Alliance for Life and Health Sciences (AVIESAN) Plan Cancer 2014-2019; US National Cancer Institute, National Institutes of Health; the James C. Bradford Jr. Melanoma Fund; and the Melanoma Research Foundation