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"Cope, Andrew"
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The little book of being brilliant
\"As a seasoned author, Andy is going to extraordinary lengths to avoid Deja Moo the feeling that youve heard all this bull-shit before. He describes the new book thus: Im a big Led Zep fan but I dont want their entire back catalogue because some of the early stuff makes my ears bleed. Ditto positive psychology. Theres an awful lot of content out there so this is my Greatest Hits CD. The very best bits from the fields of wellbeing and happiness, with no filler. The book will contain the very latest from the science of positive psychology, including insights from his own research, plus an array of material begged, borrowed and rehashed from academia and self-help. Andys specialisms of attitudinal choice, emotional contagion, resilience, goal-setting and strengths will shine through, as will his stories, energy and humour. The book is designed to provoke thought as well as action. As such, there will be activities to complete and homework that challenges readers to embed new ways of thinking. Most of all, the reader can expect quirkiness and fun. The content will include some or all of: Why happiness is the biggest mis-selling scandal of all time Why most people are a million miles away from feeling as great as they could Happiness lessons from around the world The absolute truth about money and happiness Small changes that will super-charge your career Why zebras dont get ulcers Why you should stick up for Mondays How to create a 25th hour How to cure road rage (and all other types of rage) Top tips so you can feel amazing, often against the odds The cheats guide to positive parenting How to win the lottery guaranteed)\"-- Provided by publisher.
Book
JAK inhibitors and the risk of malignancy: a meta-analysis across disease indications
ObjectivesTo estimate the association of Janus kinase inhibitors (JAKi) with the incidence of malignancy, compared with placebo, tumour necrosis factor (TNF)-α inhibitors (TNFi) and methotrexate.MethodsSystematic searches of databases were performed, to December 2022, to identify phase II/III/IV randomised clinical trials (RCTs) and long-term extension (LTE) studies of JAKi (tofacitinib, baricitinib, upadacitinib, filgotinib, peficitinib) compared with placebo, TNFi or methotrexate, in adults with rheumatoid arthritis, psoriatic arthritis, psoriasis, axial spondyloarthritis, inflammatory bowel disease or atopic dermatitis. Network and pairwise meta-analyses were performed to estimate incidence rate ratios (IRRs) for malignancy between JAKi and comparators. Bias was assessed using the Cochrane Risk of Bias-2 tool.ResultsIn 62 eligible RCTs and 16 LTE studies, there were 82 366 person-years of exposure to JAKi, 2924 to placebo, 7909 to TNFi and 1074 to methotrexate. The overall malignancy incidence rate was 1.15 per 100 person-years in RCTs, and 1.26 per 100 person-years across combined RCT and LTE data. In network meta-analyses, the incidence of all malignancies including non-melanomatous skin cancers (NMSCs) was not significantly different between JAKi and placebo (IRR 0.71; 95% CI 0.44 to 1.15) or between JAKi and methotrexate (IRR 0.77; 95% CI 0.35 to 1.68). Compared with TNFi, however, JAKi were associated with an increased incidence of malignancy (IRR 1.50; 95% CI 1.16 to 1.94). Findings were consistent when analysing NMSC only and when analysing combined RCT/LTE data.ConclusionsJAKi were associated with a higher incidence of malignancy compared with TNFi but not placebo or methotrexate. Cancers were rare events in all comparisons.PROSPERO registration numberCRD42022362630.
Journal Article
Shine : rediscovering your energy, happiness & purpose
\"Start living the life youve always wanted It could be that youve figured everything out on your own and have ended up acing your career, meeting and marrying your perfect partner, producing three wonderful kids, owning a holiday home in Mustique and having a drop-dead gorgeous life. In which case, we applaud you. If, on the other hand, you need the cheat codes, then this book will give you a nudge. Redefining the genre of self-help comedy, Shine is a book about the brevity of life. It contains adult themes of mortality, change, exhaustion and unrelenting pressure. Thankfully, the bleakness is done with humour and the solutions are entertaining, do-able and uplifting. Shine is the literary equivalent of ctrl/alt/delete. All you have to do is read the book, keep an open mind, and apply the learning. You will experience a personal re-boot with new mental software installed, upgrading you to best possible self. Its a very simple process that also happens to be not very easy. Because, of course, if being your best self was easy, everybody would be doing it. The average lifespan is 4000 weeks. Look around and youll see too many people having a near life experience. They're alive, but not living. Truth time: life's a short and precious gift that's hurtling by in a blur. If you want to make a dent in the universe, it's time to wake up. We figure that if youre going to rise, you may as well shine. Laugh and learn while you: Rediscover your ability to ping out of bed every single day with fire in your belly and a smile on your face. Identify what really matters in your life and how to stop stressing about the stuff that doesn't. Remember how to focus on all that makes you happy and cut the nonsense that worries you for no reason. Give up your low-level grumbling and experience the joy that comes when you focus on achieving all that you've ever wanted. Find out just how easy it is boost your energy and increase your motivation. Discover how to break free from 'ordinary' and embrace a life of 'extraordinary. Figure out how to channel your inner Mary Poppins\"-- Provided by publisher.
Book
EULAR points to consider for the diagnosis and management of rheumatic immune-related adverse events due to cancer immunotherapy with checkpoint inhibitors
BackgroundRheumatic and musculoskeletal immune-related adverse events (irAEs) are observed in about 10% of patients with cancer receiving checkpoint inhibitors (CPIs). Given the recent emergence of these events and the lack of guidance for rheumatologists addressing them, a European League Against Rheumatism task force was convened to harmonise expert opinion regarding their identification and management.MethodsFirst, the group formulated research questions for a systematic literature review. Then, based on literature and using a consensus procedure, 4 overarching principles and 10 points to consider were developed.ResultsThe overarching principles defined the role of rheumatologists in the management of irAEs, highlighting the shared decision-making process between patients, oncologists and rheumatologists. The points to consider inform rheumatologists on the wide spectrum of musculoskeletal irAEs, not fulfilling usual classification criteria of rheumatic diseases, and their differential diagnoses. Early referral and facilitated access to rheumatologist are recommended, to document the target organ inflammation. Regarding therapeutic, three treatment escalations were defined: (1) local/systemic glucocorticoids if symptoms are not controlled by symptomatic treatment, then tapered to the lowest efficient dose, (2) conventional synthetic disease-modifying antirheumatic drugs, in case of inadequate response to glucocorticoids or for steroid sparing and (3) biological disease-modifying antirheumatic drugs, for severe or refractory irAEs. A warning has been made on severe myositis, a life-threatening situation, requiring high dose of glucocorticoids and close monitoring. For patients with pre-existing rheumatic disease, baseline immunosuppressive regimen should be kept at the lowest efficient dose before starting immunotherapies.ConclusionThese statements provide guidance on diagnosis and management of rheumatic irAEs and aim to support future international collaborations.
Journal Article
Manus x machina : fashion in an age of technology
\"The catalogue that accompanies the 2016 Costume Institute exhibition \"Manus x Machina\" features exceptional fashions that reconcile traditional hand techniques with innovative machine technologies such as 3-D printing, laser cutting, circular knitting, computer modeling, bonding and laminating, and ultrasonic welding. Featuring 90 astonishing pieces, ranging from Gabrielle \"Coco\" Chanel's iconic tweed suit to Karl Lagerfeld's 3-D-printed version, and from Yves Saint Laurent's bird-of-paradise dress to Iris van Herpen's silicone adaptation - all beautifully photographed by Nicholas Alan Cope - this fascinating book is an exploration of both the artistry and the future of fashion. Interviews with Sarah Burton of Alexander McQueen; Hussein Chalayan, Maria Grazia Chiuri, and Pierpaolo Piccioli of Valentino; Nicolas Ghesquiلere of Louis Vuitton; Lazaro Hernandez and Jack McCollough of Proenza Schouler; Iris van Herpen; Christopher Kane; Karl Lagerfeld of Chanel; Miuccia Prada; and Gareth Pugh enhance this expansive and absorbing book.\" -- Publisher's description
Book
Monocytes Induce STAT3 Activation in Human Mesenchymal Stem Cells to Promote Osteoblast Formation
A major therapeutic challenge is how to replace bone once it is lost. Bone loss is a characteristic of chronic inflammatory and degenerative diseases such as rheumatoid arthritis and osteoporosis. Cells and cytokines of the immune system are known to regulate bone turnover by controlling the differentiation and activity of osteoclasts, the bone resorbing cells. However, less is known about the regulation of osteoblasts (OB), the bone forming cells. This study aimed to investigate whether immune cells also regulate OB differentiation. Using in vitro cell cultures of human bone marrow-derived mesenchymal stem cells (MSC), it was shown that monocytes/macrophages potently induced MSC differentiation into OBs. This was evident by increased alkaline phosphatase (ALP) after 7 days and the formation of mineralised bone nodules at 21 days. This monocyte-induced osteogenic effect was mediated by cell contact with MSCs leading to the production of soluble factor(s) by the monocytes. As a consequence of these interactions we observed a rapid activation of STAT3 in the MSCs. Gene profiling of STAT3 constitutively active (STAT3C) infected MSCs using Illumina whole human genome arrays showed that Runx2 and ALP were up-regulated whilst DKK1 was down-regulated in response to STAT3 signalling. STAT3C also led to the up-regulation of the oncostatin M (OSM) and LIF receptors. In the co-cultures, OSM that was produced by monocytes activated STAT3 in MSCs, and neutralising antibodies to OSM reduced ALP by 50%. These data indicate that OSM, in conjunction with other mediators, can drive MSC differentiation into OB. This study establishes a role for monocyte/macrophages as critical regulators of osteogenic differentiation via OSM production and the induction of STAT3 signalling in MSCs. Inducing the local activation of STAT3 in bone cells may be a valuable tool to increase bone formation in osteoporosis and arthritis, and in localised bone remodelling during fracture repair.
Journal Article
In pursuit of fashion : The Sandy Schreier collection
Presenting outstanding costumes and insightful texts about one of the greatest private collections of 20th-century fashion. This handsome volume explores the modern discipline of fashion collecting and the value of the collector's eye by presenting remarkable works from the greatest private collection of 20th-century costume. This unique group of clothing and accessories, assembled over several decades by Sandy Schreier, includes many rare and historically significant pieces that define key moments in fashion. Her collections features not only iconic garments by established designers but also looks by pioneering couturiers rarely represented in museum collections. Outstanding works, by designers that include Gilbert Adrian, Cristobal Balenciaga, Boue Soeurs, Gabrielle \"Coco\" Chanel, Christian Dior, Mariano Fortuny, Karl Lagerfeld, Paul Poiret, and Valentina, are illustrated with stunning new photography by fashion photographer Nicholas Cope. An informative introduction traces the progress of her collecting from its roots in Detroit to the present day. The book also includes descriptions of over 80 works, including costumes, accessories, and rare designer drawings, in addition to a lively interview with Schreier by Andrew Bolton that reveals her collecting philosophy.
Book
EULAR points to consider for conducting clinical trials and observational studies in individuals at risk of rheumatoid arthritis
BackgroundDespite growing interest, there is no guidance or consensus on how to conduct clinical trials and observational studies in populations at risk of rheumatoid arthritis (RA).MethodsAn European League Against Rheumatism (EULAR) task force formulated four research questions to be addressed by systematic literature review (SLR). The SLR results informed consensus statements. One overarching principle, 10 points to consider (PTC) and a research agenda were proposed. Task force members rated their level of agreement (1–10) for each PTC.ResultsEpidemiological and demographic characteristics should be measured in all clinical trials and studies in at-risk individuals. Different at-risk populations, identified according to clinical presentation, were defined: asymptomatic, musculoskeletal symptoms without arthritis and early clinical arthritis. Study end-points should include the development of subclinical inflammation on imaging, clinical arthritis, RA and subsequent achievement of arthritis remission. Risk factors should be assessed at baseline and re-evaluated where appropriate; they include genetic markers and autoantibody profiling and additionally clinical symptoms and subclinical inflammation on imaging in those with symptoms and/or clinical arthritis. Trials should address the effect of the intervention on risk factors, as well as progression to clinical arthritis or RA. In patients with early clinical arthritis, pharmacological intervention has the potential to prevent RA development. Participants’ knowledge of their RA risk may inform their decision to participate; information should be provided using an individually tailored approach.ConclusionThese consensus statements provide data-driven guidance for rheumatologists, health professionals and investigators conducting clinical trials and observational studies in individuals at risk of RA.
Journal Article
Associations between immune-suppressive and stimulating drugs and novel COVID-19—a systematic review of current evidence
Cancer and transplant patients with COVID-19 have a higher risk of developing severe and even fatal respiratory diseases, especially as they may be treated with immune-suppressive or immune-stimulating drugs. This review focuses on the effects of these drugs on host immunity against COVID-19.
Using Ovid MEDLINE, we reviewed current evidence for immune-suppressing or -stimulating drugs: cytotoxic chemotherapy, low-dose steroids, tumour necrosis factorα (TNFα) blockers, interlukin-6 (IL-6) blockade, Janus kinase (JAK) inhibitors, IL-1 blockade, mycophenolate, tacrolimus, anti-CD20 and CTLA4-Ig.
89 studies were included. Cytotoxic chemotherapy has been shown to be a specific inhibitor for severe acute respiratory syndrome coronavirus in in vitro studies, but no specific studies exist as of yet for COVID-19. No conclusive evidence for or against the use of non-steroidal anti-inflammatory drugs (NSAIDs) in the treatment of COVID-19 patients is available, nor is there evidence indicating that TNFα blockade is harmful to patients in the context of COVID-19. COVID-19 has been observed to induce a pro-inflammatory cytokine generation and secretion of cytokines, such as IL-6, but there is no evidence of the beneficial impact of IL-6 inhibitors on the modulation of COVID-19. Although there are potential targets in the JAK-STAT pathway that can be manipulated in treatment for coronaviruses and it is evident that IL-1 is elevated in patients with a coronavirus, there is currently no evidence for a role of these drugs in treatment of COVID-19.
The COVID-19 pandemic has led to challenging decision-making about treatment of critically unwell patients. Low-dose prednisolone and tacrolimus may have beneficial impacts on COVID-19. The mycophenolate mofetil picture is less clear, with conflicting data from pre-clinical studies. There is no definitive evidence that specific cytotoxic drugs, low-dose methotrexate for auto-immune disease, NSAIDs, JAK kinase inhibitors or anti-TNFα agents are contraindicated. There is clear evidence that IL-6 peak levels are associated with severity of pulmonary complications.
Journal Article
Cholesterol metabolism drives regulatory B cell IL-10 through provision of geranylgeranyl pyrophosphate
Regulatory B cells restrict immune and inflammatory responses across a number of contexts. This capacity is mediated primarily through the production of IL-10. Here we demonstrate that the induction of a regulatory program in human B cells is dependent on a metabolic priming event driven by cholesterol metabolism. Synthesis of the metabolic intermediate geranylgeranyl pyrophosphate (GGPP) is required to specifically drive IL-10 production, and to attenuate Th1 responses. Furthermore, GGPP-dependent protein modifications control signaling through PI3Kδ-AKT-GSK3, which in turn promote BLIMP1-dependent IL-10 production. Inherited gene mutations in cholesterol metabolism result in a severe autoinflammatory syndrome termed mevalonate kinase deficiency (MKD). Consistent with our findings, B cells from MKD patients induce poor IL-10 responses and are functionally impaired. Moreover, metabolic supplementation with GGPP is able to reverse this defect. Collectively, our data define cholesterol metabolism as an integral metabolic pathway for the optimal functioning of human IL-10 producing regulatory B cells.
IL-10 production by B cells is integral to regulation and resolution of inflammation. Here the authors show that cholesterol metabolism can control B cell IL-10 production via a geranylgeranyl pyrophosphate-dependent mechanism.
Journal Article