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Small studies suggest peanut oral immunotherapy (OIT) might be effective in the treatment of peanut allergy. We aimed to establish the efficacy of OIT for the desensitisation of children with allergy to peanuts. We did a randomised controlled crossover trial to compare the efficacy of active OIT (using characterised peanut flour; protein doses of 2–800 mg/day) with control (peanut avoidance, the present standard of care) at the NIHR/Wellcome Trust Cambridge Clinical Research Facility (Cambridge, UK). Randomisation (1:1) was by use of an audited online system; group allocation was not masked. Eligible participants were aged 7–16 years with an immediate hypersensitivity reaction after peanut ingestion, positive skin prick test to peanuts, and positive by double-blind placebo-controlled food challenge (DBPCFC). We excluded participants if they had a major chronic illness, if the care provider or a present household member had suspected or diagnosed allergy to peanuts, or if there was an unwillingness or inability to comply with study procedures. Our primary outcome was desensitisation, defined as negative peanut challenge (1400 mg protein in DBPCFC) at 6 months (first phase). Control participants underwent OIT during the second phase, with subsequent DBPCFC. Immunological parameters and disease-specific quality-of-life scores were measured. Analysis was by intention to treat. Fisher's exact test was used to compare the proportion of those with desensitisation to peanut after 6 months between the active and control group at the end of the first phase. This trial is registered with Current Controlled Trials, number ISRCTN62416244. The primary outcome, desensitisation, was recorded for 62% (24 of 39 participants; 95% CI 45–78) in the active group and none of the control group after the first phase (0 of 46; 95% CI 0–9; p<0·001). 84% (95% CI 70–93) of the active group tolerated daily ingestion of 800 mg protein (equivalent to roughly five peanuts). Median increase in peanut threshold after OIT was 1345 mg (range 45–1400; p<0·001) or 25·5 times (range 1·82–280; p<0·001). After the second phase, 54% (95% CI 35–72) tolerated 1400 mg challenge (equivalent to roughly ten peanuts) and 91% (79–98) tolerated daily ingestion of 800 mg protein. Quality-of-life scores improved (decreased) after OIT (median change −1·61; p<0·001). Side-effects were mild in most participants. Gastrointestinal symptoms were, collectively, most common (31 participants with nausea, 31 with vomiting, and one with diarrhoea), then oral pruritus after 6·3% of doses (76 participants) and wheeze after 0·41% of doses (21 participants). Intramuscular adrenaline was used after 0·01% of doses (one participant). OIT successfully induced desensitisation in most children within the study population with peanut allergy of any severity, with a clinically meaningful increase in peanut threshold. Quality of life improved after intervention and there was a good safety profile. Immunological changes corresponded with clinical desensitisation. Further studies in wider populations are recommended; peanut OIT should not be done in non-specialist settings, but it is effective and well tolerated in the studied age group. MRC-NIHR partnership.

This paper presents the results to date of the RepRap project – an ongoing project that has made and distributed freely a replicating rapid prototyper. We give the background reasoning that led to the invention of the machine, the selection of the processes that we and others have used to implement it, the designs of key parts of the machine and how these have evolved from their initial concepts and experiments, and estimates of the machine's reproductive success out in the world up to the time of writing (about 4500 machines in two and a half years).

Ecological models of competition have provided great explanatory power regarding synonymy in derivational morphology. Competition models of this type have certainly shown their utility, as they have demonstrated, among other things, the relevance of frequency measures, productivity, compositionality and analyzability when comparing the development of morphological constructions. There has been less consideration of alternative models that could be used to describe the historical co-development of suffixes that produce words with sometimes similar forms or meanings but are not inevitably or solely in competition. The symbiotic model proposed in this article may help answer larger questions in linguistics, such as how best to analyze certain multilingual morphological phenomena, including the emergence of semantically similar forms within the same language. The present study demonstrates the importance of a diachronic approach in situations of near-synonymy, as an understanding of semantic similarity necessitates a review of the available historical record. In particular, our study focuses on the case of the suffix -eer (e.g., marketeer) in English, analyzing its origins, semantics, compositionality, and historical development, including its symbiotic relationship to the similar suffix -er (e.g., marketer).

From the archives of Golf Channel comes the ultimate book on the sport--a must for every fan--a comprehensive and engaging full-color compendium of the best moments of the past 20 years, filled with stories from top players, colorful insights from on air talent and celebrity viewers, essential lists and sidebars, and stunning photographs of legendary golf courses around the world. Foreword by Arnold Palmer. Over the past two decades, golf has witnessed some of the most exciting play, interesting players, biggest technological advances, deepest controversies, increased participation and viewership, and unprecedented engagement between professionals and fans in its history. Year by year, shot by shot around the globe, Golf Channel has been there to cover it all. Now, for the first time, the network that features more live golf coverage than all others combined opens its archives and offers unprecedented access to its top on air talent. The result is a dazzling illustrated digest that pays tribute to the sport and the extraordinary players and events that have shaped it over the course of a generation.

To determine whether the introduction of the Universal Form of Treatment Options (the UFTO), as an alternative approach to Do Not Attempt Cardiopulmonary Resuscitation (DNACPR) orders, reduces harms in patients in whom a decision not to attempt cardiopulmonary resuscitation (CPR) was made, and to understand the mechanism for any observed change. A mixed-methods before-and-after study with contemporaneous case controls was conducted in an acute hospital. We examined DNACPR (103 patients with DNACPR orders in 530 admissions) and UFTO (118 decisions not to attempt resuscitation in 560 admissions) practice. The Global Trigger Tool was used to quantify harms. Qualitative interviews and observations were used to understand mechanisms and effects. RATE OF HARMS IN PATIENTS FOR WHOM THERE WAS A DOCUMENTED DECISION NOT TO ATTEMPT CPR WAS REDUCED: Rate difference per 1000 patient-days was 12.9 (95% CI: 2.6-23.2, p-value=0.01). There was a difference in the proportion of harms contributing to patient death in the two periods (23/71 in the DNACPR period to 4/44 in the UFTO period (95% CI 7.8-36.1, p-value=0.006). Significant differences were maintained after adjustment for known confounders. No significant change was seen on contemporaneous case control wards. Interviews with clinicians and observation of ward practice revealed the UFTO helped provide clarity of goals of care and reduced negative associations with resuscitation decisions. Introducing the UFTO was associated with a significant reduction in harmful events in patients in whom a decision not to attempt CPR had been made. Coupled with supportive qualitative evidence, this indicates the UFTO improved care for this vulnerable group. Controlled-Trials.com ISRCTN85474986 UK Comprehensive Research Network Portfolio 7932.

One of comics' wildest writers takes on the symbiotic super hero! Flash Thompson, the Secret Avenger called Agent Venom, faces Daimon Hellstrom and the Monsters of Evil in a battle to save his soul! But when Venom's psychopathic off spring targets the Microverse, Flash and the new Scarlet Spider must put their rivalries aside to handle the madness of Carnage! Venom says farewell to New York and heads to Philadelphia - but Toxin follows soon after. And the pair of lethal symbiotes may unwittingly unleash something even more deadly! Can Flash battle side-by-side with the original Venom, Eddie Brock, to save the City of Brotherly Love? Plus underworld boss Lord Ogre! The killer called Crossbones! And...a symbiotic sidekick?! Cullen Bunn's explosive Venom run is collected in full!

Ecological models of competition have provided great explanatory power regarding synonymy in derivational morphology. Competition models of this type have certainly shown their utility, as they have demonstrated, among other things, the relevance of frequency measures, productivity, compositionality and analyzability when comparing the development of morphological constructions. There has been less consideration of alternative models that could be used to describe the historical co-development of suffixes that produce words with sometimes similar forms or meanings but are not inevitably or solely in competition. The symbiotic model proposed in this article may help answer larger questions in linguistics, such as how best to analyze certain multilingual morphological phenomena, including the emergence of semantically similar forms within the same language. The present study demonstrates the importance of a diachronic approach in situations of near-synonymy, as an understanding of semantic similarity necessitates a review of the available historical record. In particular, our study focuses on the case of the suffix -eer (e.g., marketeer) in English, analyzing its origins, semantics, compositionality, and historical development, including its symbiotic relationship to the similar suffix -er (e.g., marketer).