Numerical Simulation of Flow Control by Synthetic Jet Actuation

Numerical simulations of active flow control have been carried out for the flow around the NACA0018 profile for Mach = 0.15, Re = 2× 106, a = 15o using the Unsteady Reynolds Averaged Navier-Stokes (URANS) equations. Two types of flow control, zero-net-mass jets (synthetic jets) and continuously blowing jets, have been considered to delay the onset of separation. The synthetic jets have been applied to the 2D situation, i.e. infinitely long slits in the spanwise, for which the angle between the jet and surface normal has been varied to study the effect on the separation. For the continuously blowing jets the effect of 3D mixing is taken into account and an optimization of several jet parameters has been carried out to obtain the best result possible

The psychological burden of skin diseases: a cross-sectional multicenter study among dermatological out-patients in 13 European countries.

The contribution of psychological disorders to the burden of skin disease has been poorly explored, and this is a large-scale study to ascertain the association between depression, anxiety, and suicidal ideation with various dermatological diagnoses. This international multicenter observational cross-sectional study was conducted in 13 European countries. In each dermatology clinic, 250 consecutive adult out-patients were recruited to complete a questionnaire, reporting socio-demographic information, negative life events, and suicidal ideation; depression and anxiety were assessed with the Hospital Anxiety and Depression Scale. A clinical examination was performed. A control group was recruited among hospital employees. There were 4,994 participants--3,635 patients and 1,359 controls. Clinical depression was present in 10.1% patients (controls 4.3%, odds ratio (OR) 2.40 (1.67-3.47)). Clinical anxiety was present in 17.2% (controls 11.1%, OR 2.18 (1.68-2.82)). Suicidal ideation was reported by 12.7% of all patients (controls 8.3%, OR 1.94 (1.33-2.82)). For individual diagnoses, only patients with psoriasis had significant association with suicidal ideation. The association with depression and anxiety was highest for patients with psoriasis, atopic dermatitis, hand eczema, and leg ulcers. These results identify a major additional burden of skin disease and have important clinical implications.Peer reviewedFinal Published versio

Flow cytometric immunobead assay for fast and easy detection of PML-RARA fusion proteins for the diagnosis of acute promyelocytic leukemia

The PML-RARA fusion protein is found in approximately 97% of patients with acute promyelocytic leukemia (APL). APL can be associated with life-threatening bleeding complications when undiagnosed and not treated expeditiously. The PML-RARA fusion protein arrests maturation of myeloid cells at the promyelocytic stage, leading to the accumulation of neoplastic promyelocytes. Complete remission can be obtained by treatment with all-trans-retinoic acid (ATRA) in combination with chemotherapy. Diagnosis of APL is based on the detection of t(15;17) by karyotyping, fluorescence in situ hybridization or PCR. These techniques are laborious and demand specialized laboratories. We developed a fast (performed within 4-5 h) and sensitive (detection of at least 10% malignant cells in normal background) flow cytometric immunobead assay for the detection of PML-RARA fusion proteins in cell lysates using a bead-bound anti-RARA capture antibody and a phycoerythrin-conjugated anti-PML detection antibody. Testing of 163 newly diagnosed patients (including 46 APL cases) with the PML-RARA immunobead assay showed full concordance with the PML-RARA PCR results. As the applied antibodies recognize outer domains of the fusion protein, the assay appeared to work independently of the PML gene break point region. Importantly, the assay can be used in parallel with routine immunophenotyping for fast and easy diagnosis of APL

Body dysmorphia in common skin diseases: Results of an observational, cross-sectional multi-centre study among dermatological out-patients in 17 European countries

Background Body dysmorphic disorder (BDD) is a common psychiatric disorder associated with high costs for healthcare systems as patients may repeatedly ask for different, often not effective interventions. BDD symptoms are more prevalent in patients with dermatological conditions than the general population, but there are no large sample studies comparing the prevalence of BDD symptoms between patients with dermatological conditions and healthy skin controls. Objectives To compare the prevalence of BDD symptoms between patients with different dermatological conditions and healthy skin controls and to describe sociodemographic, physical and psychological factors associated with BDD symptoms to identify patients who may have a particularly high chance of having this condition. Methods This observational cross-sectional, comparative multi-centre study included 8295 participants: 5487 consecutive patients with different skin diseases (56% female) recruited among dermatological out-patients at 22 clinics in 17 European countries and 2808 healthy skin controls (66% female). All patients were examined by a dermatologist. BDD symptoms were assessed by the Dysmorphic Concern Questionnaire (DCQ). Sociodemographic data, information on psychological factors and physical conditions were collected. Each patient was given a dermatological diagnosis according to ICD-10 by a dermatologist. Results The participation rate of invited dermatological patients was 82.4% on average across all centres. BDD symptoms were five times more prevalent in patients with dermatological conditions than in healthy skin controls (10.5% vs. 2.1%). Patients with hyperhidrosis, alopecia and vitiligo had a more than eleven-fold increased chance (adjusted Odds Ratio (OR) > 11) of having BDD symptoms compared to healthy skin controls, and patients with atopic dermatitis, psoriasis, acne, hidradenitis suppurativa, prurigo and bullous diseases had a more than six-fold increased chance (adjusted OR > 6) of having BDD symptoms. Using a logistic regression model, BDD symptoms were significantly related to lower age, female sex, higher psychological stress and feelings of stigmatisation. Conclusions This study reveals that clinical BDD symptoms are significantly associated with common dermatological diseases. As such symptoms are associated with higher levels of psychological distress and multiple unhelpful consultations, general practitioners and dermatologists should consider BDD and refer patients when identified to an appropriate service for BDD screening and management

Bi-allelic Loss-of-Function CACNA1B Mutations in Progressive Epilepsy-Dyskinesia.

The occurrence of non-epileptic hyperkinetic movements in the context of developmental epileptic encephalopathies is an increasingly recognized phenomenon. Identification of causative mutations provides an important insight into common pathogenic mechanisms that cause both seizures and abnormal motor control. We report bi-allelic loss-of-function CACNA1B variants in six children from three unrelated families whose affected members present with a complex and progressive neurological syndrome. All affected individuals presented with epileptic encephalopathy, severe neurodevelopmental delay (often with regression), and a hyperkinetic movement disorder. Additional neurological features included postnatal microcephaly and hypotonia. Five children died in childhood or adolescence (mean age of death: 9 years), mainly as a result of secondary respiratory complications. CACNA1B encodes the pore-forming subunit of the pre-synaptic neuronal voltage-gated calcium channel Cav2.2/N-type, crucial for SNARE-mediated neurotransmission, particularly in the early postnatal period. Bi-allelic loss-of-function variants in CACNA1B are predicted to cause disruption of Ca2+ influx, leading to impaired synaptic neurotransmission. The resultant effect on neuronal function is likely to be important in the development of involuntary movements and epilepsy. Overall, our findings provide further evidence for the key role of Cav2.2 in normal human neurodevelopment.MAK is funded by an NIHR Research Professorship and receives funding from the Wellcome Trust, Great Ormond Street Children's Hospital Charity, and Rosetrees Trust. E.M. received funding from the Rosetrees Trust (CD-A53) and Great Ormond Street Hospital Children's Charity. K.G. received funding from Temple Street Foundation. A.M. is funded by Great Ormond Street Hospital, the National Institute for Health Research (NIHR), and Biomedical Research Centre. F.L.R. and D.G. are funded by Cambridge Biomedical Research Centre. K.C. and A.S.J. are funded by NIHR Bioresource for Rare Diseases. The DDD Study presents independent research commissioned by the Health Innovation Challenge Fund (grant number HICF-1009-003), a parallel funding partnership between the Wellcome Trust and the Department of Health, and the Wellcome Trust Sanger Institute (grant number WT098051). We acknowledge support from the UK Department of Health via the NIHR comprehensive Biomedical Research Centre award to Guy's and St. Thomas' National Health Service (NHS) Foundation Trust in partnership with King's College London. This research was also supported by the NIHR Great Ormond Street Hospital Biomedical Research Centre. J.H.C. is in receipt of an NIHR Senior Investigator Award. The research team acknowledges the support of the NIHR through the Comprehensive Clinical Research Network. The views expressed are those of the author(s) and not necessarily those of the NHS, the NIHR, Department of Health, or Wellcome Trust. E.R.M. acknowledges support from NIHR Cambridge Biomedical Research Centre, an NIHR Senior Investigator Award, and the University of Cambridge has received salary support in respect of E.R.M. from the NHS in the East of England through the Clinical Academic Reserve. I.E.S. is supported by the National Health and Medical Research Council of Australia (Program Grant and Practitioner Fellowship)

Whole-genome sequencing reveals host factors underlying critical COVID-19

Critical COVID-19 is caused by immune-mediated inflammatory lung injury. Host genetic variation influences the development of illness requiring critical care1 or hospitalization2,3,4 after infection with SARS-CoV-2. The GenOMICC (Genetics of Mortality in Critical Care) study enables the comparison of genomes from individuals who are critically ill with those of population controls to find underlying disease mechanisms. Here we use whole-genome sequencing in 7,491 critically ill individuals compared with 48,400 controls to discover and replicate 23 independent variants that significantly predispose to critical COVID-19. We identify 16 new independent associations, including variants within genes that are involved in interferon signalling (IL10RB and PLSCR1), leucocyte differentiation (BCL11A) and blood-type antigen secretor status (FUT2). Using transcriptome-wide association and colocalization to infer the effect of gene expression on disease severity, we find evidence that implicates multiple genes—including reduced expression of a membrane flippase (ATP11A), and increased expression of a mucin (MUC1)—in critical disease. Mendelian randomization provides evidence in support of causal roles for myeloid cell adhesion molecules (SELE, ICAM5 and CD209) and the coagulation factor F8, all of which are potentially druggable targets. Our results are broadly consistent with a multi-component model of COVID-19 pathophysiology, in which at least two distinct mechanisms can predispose to life-threatening disease: failure to control viral replication; or an enhanced tendency towards pulmonary inflammation and intravascular coagulation. We show that comparison between cases of critical illness and population controls is highly efficient for the detection of therapeutically relevant mechanisms of disease

On the hyacinth macaw's nesting tree: density of young manduvis around adult trees under three different management conditions in the Pantanal wetland, Brazil.

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