SUMMARYThis 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).

SummaryBackgroundSmall 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.MethodsWe 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.FindingsThe 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).InterpretationOIT 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 d...

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* The reason for the fall in death rates from stroke in industrialised countries is unclear * In this study blood pressure and smoking were independent risk factors for stroke in both sexes and serum cholesterol concentration was also a risk factor in men * Mortality fell by 62% in men and 63% in women over 20 years * Changes in risk factors explained 71% ofthe fall in men and 54% in women * Continued emphasis on promoting healthier lifestyles and effective treatment for hypertension are essential to maintain the fall in deaths representative of development in the entire country. It should not be taken for granted that the decreasing trend will automatically continue. Our data show that the fall will continue only if preventive measures targeted on the primary risk factors, particularly on blood pressure, are effective.

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Perceptual decisions are likely to be based on signals that are provided by populations of neurons in early sensory cortical areas. How these neural responses are combined across neurons and over time to mediate behavior is unknown. To study the link between neural responses and perceptual decisions, we recorded the activity of single units (SU) and multiple units (MU) in the primary visual cortex (V1) of monkeys while they performed a reaction-time visual detection task. We then determined how well the target could be detected from these neural signals. We found that, on average, the detection sensitivities supported by SU and MU in V1 are comparable with the detection sensitivity of the monkey even when considering neural responses during brief temporal intervals (median duration, 137 ms) that ended shortly before the monkey's reaction time. However, we observed systematic differences between the overall shape of the neurometric functions and the monkey's psychometric functions. We also examined the quantitative relationship between SU and MU activity and found that MU responses are consistent with the sum of the responses of multiple SU, most of which have low stimulus selectivity. Finally, we found weak but significant trial-to-trial covariations between V1 activity and behavioral choices, demonstrating for the first time that choice probability can be observed at the earliest stages of cortical sensory processing. Together, these results suggest that the activity of a large population of V1 neurons is combined suboptimally by subsequent processing stages to mediate behavioral performance in visual detection tasks.

AimsTo 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.MethodsA 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.ResultsRate 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.ConclusionsIntroducing 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.Trial RegistrationControlled-Trials.com ISRCTN85474986 UK Comprehensive Research Network Portfolio 7932

Objectives-To study circumstances of bicycle accidents and nature of injuries sustained and to determine effect of safety helmets on pattern of miuries.Design-Prospective study of patients with cycle related injuries.Setting-Accident and emergency departnent of teaching hospital.Subjects-1040 patients with complete data presenting to the department in one year with cycle related injuries, ofwhom 114 had worn cycle helmets when accident occurred.Main outcome measures-Type of accident and nature and distribution of injuries among patients with and without safety helmets.Results-There were no significant differences between the two groups with respect to type of