The Happipreneur

The book charts his fascinating life from CEO and global Rockstar of Amway to his off the cuff #MicroBizMatters events. Exposing how business owners are conned out of their money by “industry advisers” and often forced into debt. A modern and up to date take on Small is Beautiful by EF Schumacher. Both authors agree that no-one can afford to wait for the revolution any more than they can afford to wait for a vaccine. Johnston explained: ‘As business owners, Tony, myself and all our readers have to just get on with it. It is always a rollercoaster and we expect the unexpected. We hope our guide helps them to avoid the snakes and climb the ladders. Tony’s story of what he has learned from his own businesses and working with many famous entrepreneurs is important for others to know. It is about how to live an enterprising and happy life. We answer the question ‘How to become a Happipreneur?’. We call out the fakes and the scammers and provide a blueprint for the Establishment on why and how they can level the playing field.” An insight into the life of a man who has dedicated the last 30 years to improving the way MicroBiz owners are treated but is also a no-nonsense guide to avoiding the pitfalls small business owners face. “Masturbation is good but Musturbation is bad” Albert Ellis describes the three things that hold us back: I must do well. You must treat me well and the world must be easy. This book is not only an insight into the life of a man who has dedicated the last 30 years to improving the way MicroBiz owners are treated; but is also a no-nonsense guide to avoiding the pitfalls small business owners face. Tony has lived, without a doubt, an incredibly interesting and diverse life, from being the CEO of a huge corporation to almost single-handedly campaigning for the little guy

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

Altres ajuts: Department of Health and Social Care (DHSC); Illumina; LifeArc; Medical Research Council (MRC); UKRI; Sepsis Research (the Fiona Elizabeth Agnew Trust); the Intensive Care Society, Wellcome Trust Senior Research Fellowship (223164/Z/21/Z); BBSRC Institute Program Support Grant to the Roslin Institute (BBS/E/D/20002172, BBS/E/D/10002070, BBS/E/D/30002275); UKRI grants (MC_PC_20004, MC_PC_19025, MC_PC_1905, MRNO2995X/1); UK Research and Innovation (MC_PC_20029); the Wellcome PhD training fellowship for clinicians (204979/Z/16/Z); the Edinburgh Clinical Academic Track (ECAT) programme; the National Institute for Health Research, the Wellcome Trust; the MRC; Cancer Research UK; the DHSC; NHS England; the Smilow family; the National Center for Advancing Translational Sciences of the National Institutes of Health (CTSA award number UL1TR001878); the Perelman School of Medicine at the University of Pennsylvania; National Institute on Aging (NIA U01AG009740); the National Institute on Aging (RC2 AG036495, RC4 AG039029); the Common Fund of the Office of the Director of the National Institutes of Health; NCI; NHGRI; NHLBI; NIDA; NIMH; NINDS.Critical COVID-19 is caused by immune-mediated inflammatory lung injury. Host genetic variation influences the development of illness requiring critical care or hospitalization 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