Objective To assess the effects of interventions to promote walking in individuals and populations. Design Systematic review. Data sources Published and unpublished reports in any language identified by searching 25 electronic databases, by searching websites, reference lists, and existing systematic reviews, and by contacting experts. Review methods Systematic search for and appraisal of controlled before and after studies of the effects of any type of intervention on how much people walk, the distribution of effects on walking between social groups, and any associated effects on overall physical activity, fitness, risk factors for disease, health, and wellbeing.
The requirement for sequence specificity in the AAUAAA motif of the cauliflower mosaic virus (CaMV) polyadenylation signal was examined by saturation mutagenesis. While deletion of AAUAAA almost abolished processing at the CaMV polyadenylation site, none of the 18 possible single base mutations had a dramatic effect on processing efficiency. The effect of replacing all six nucleotides simultaneously varied depending on the sequence used, but some replacements were as detrimental as the deletion mutant. Taken together, these results confirm that AAUAAA is an essential component of the CaMV polyadenylation signal, but indicate that a high degree of sequence variation can be tolerated. A repeated UUUGUA motif was identified as an important upstream accessory element of the CaMV polyadenylation signal. This sequence was able to induce processing at a heterologous polyadenylation site in a sequence‐specific and additive manner. The effect of altering the spacing between this upstream element and the AAUAAA was examined; moving these two elements closer together or further apart reduces the processing efficiency. The upstream element does not function to signal processing at the CaMV polyadenylation site if placed downstream of the cleavage site. Analysis of further upstream sequences revealed that almost all of the 200 nt fragment required for maximal processing contributes positively to processing efficiency. Furthermore, isolated far upstream sequences distinct from UUUGUA were also able to induce processing at a heterologous polyadenylation site.
WHAT IS ALREADY KNOWN ABOUT THIS SUBJECT • Prescribing errors account for a substantial proportion of medication errors and cause the most significant problems. • There is a dearth of accurate information on the prevalence of prescribing errors, with estimates from 1 to 100% of all patients admitted to hospital. WHAT THIS STUDY ADDS • This review reports the wide ranges of error rates seen, which cannot be compared due to differences in methodology and error definitions used. • A well‐conducted study of prescribing errors by junior doctors using standard definitions and methodology is urgently needed to allow development and assessment of appropriate interventions. AIMS Prescribing errors are an important cause of patient safety incidents, generally considered to be made more frequently by junior doctors, but prevalence and causality are unclear. In order to inform the design of an educational intervention, a systematic review of the literature on prescribing errors made by junior doctors was undertaken. METHODS Searches were undertaken using the following databases: MEDLINE; EMBASE; Science and Social Sciences Citation Index; CINAHL; Health Management Information Consortium; PsychINFO; ISI Proceedings; The Proceedings of the British Pharmacological Society; Cochrane Library; National Research Register; Current Controlled Trials; and Index to Theses. Studies were selected if they reported prescribing errors committed by junior doctors in primary or secondary care, were in English, published since 1990 and undertaken in Western Europe, North America or Australasia. RESULTS Twenty‐four studies meeting the inclusion criteria were identified. The range of error rates was 2–514 per 1000 items prescribed and 4.2–82% of patients or charts reviewed. Considerable variation was seen in design, methods, error definitions and error rates reported. CONCLUSIONS The review reveals a widespread problem that does not appear to be associated with different training models, healthcare systems or infrastructure. There was a range of designs, methods, error definitions and error rates, making meaningful conclusions difficult. No definitive study of prescribing errors has yet been conducted, and is urgently needed to provide reliable baseline data for interventions aimed at reducing errors. It is vital that future research is well constructed and generalizable using standard definitions and methods.
Our understanding of how the 3' ends of mRNAs are formed in plants is rudimentary compared to what we know about this process in other eukaryotes. The salient features of plant pre-mRNAs that signal cleavage and polyadenylation remain obscure, and the biochemical mechanism is as yet wholly uncharacterized. Nevertheless, despite the lack of universally conserved cis-acting motifs, a common underlying architecture is emerging from functional analyses of plant poly(A) signals, allowing meaningful comparison with components of poly(A) signals in other eukaryotes. A plant poly(A) signal consists of one or more near-upstream elements (NUE), each directing processing at a poly(A) site a short distance downstream of it, and an extensive far-upstream element (FUE) that enhances processing efficiency at all sites. By analogy with other systems, a model for a plant 3'-end processing complex can be proposed. Plant poly(A) polymerases have been isolated and partially characterised. These, together with hints that some processing factors are conserved in different organisms, opens promising avenues toward initial characterisation of the trans-acting factors involved in 3'-end formation of mRNAs in higher plants.
The genomic RNA of tobacco mosaic virus (TMV), like that of other positive-strand RNA viruses, acts as a template for both translation and replication. The highly structured 3 untranslated region (UTR) of TMV RNAs plays an important role in both processes; it is not polyadenylated but ends with a tRNA-like structure (TLS) preceded by a conserved upstream pseudoknot domain (UPD). The TLS of tobamoviral RNAs can be specifically aminoacylated and, in this state, can interact with eukaryotic elongation factor 1A (eEF1A)/GTP with high affinity. Using a UV cross-linking assay, we detected another specific binding site for eEF1A/GTP, within the UPDs of TMV and crucifer-infecting tobamovirus (crTMV), that does not require aminoacylation. A mutational analysis revealed that UPD pseudoknot conformation and some conserved primary sequence elements are required for this interaction. Its possible role in the regulation of tobamovirus gene expression and replication is discussed.Tobacco mosaic virus (TMV), a positive-strand plant RNA virus, is the type member of the tobamovirus family in the alphavirus-like superfamily. The genomic RNA of TMV strain vulgare (U1) is 6,395 nucleotides (nt) long and encodes at least four proteins. The full-length RNA is used to produce 126-and 183-kDa RNA-dependent replicase proteins, while the 30-kDa movement protein (MP) and the 17.5-kDa coat protein are translated from 3Ј-coterminal subgenomic mRNAs. The coding region is flanked by the 5Ј untranslated region (5Ј-UTR, or ⍀) and the 3Ј-UTR, both of which are required for viral replication. TMV RNA is capped, but it lacks a 3Ј poly(A) tail. Instead, the 3Ј-UTR contains a highly structured and conserved sequence composed of several pseudoknots (PKs) of the hairpin loop type (Fig. 1) (50,54,61). The TMV U1 3Ј-UTR is comprised of two structural domains: a 3Ј-terminal domain containing two PKs important for formation of a tRNA-like structure (TLS) (21, 53), linked to an upstream PK domain (UPD)-a quasicontinuous double-helical stalk comprising three consecutive PKs (61). A similar tandem arrangement of structural units (UPD-TLS) is found in all tobamoviruses and satellites of TMV, although the sizes and numbers of PKs of the UPD are variable (26). The TLS of TMV can be aminoacylated and binds to several tRNA-specific enzymes (reviewed in reference 42). Interestingly, two of the PKs in the U1 UPD are phylogenetically conserved among all tobamoviruses, TMV satellites, and hordeiviruses in location, in structure, and even in several positions of primary sequence, strongly suggesting their functional importance (38, 61).Whether ending with a poly(A) tail or a TLS, the 3Ј terminus of the genomic RNA of positive-strand RNA viruses is generally thought to contain elements of the promoter for initiation of minus-strand viral RNA synthesis. The minimal 3Ј cis-acting element required for the initiation of negative-strand RNA synthesis on TMV genomic RNA includes the 3Ј-terminal TLS and the 3Ј-most-proximal PK structure (PK3) of the UPD (12,49,59). Destabiliza...
Abstract-Weight gain may increase blood pressure. Weight loss may reduce this. Reviews have considered the long-term effects of weight loss but are related mainly to more obese participants often on obesity medication and/or undergoing obesity surgery. This systematic review, based on lifestyle interventions for adults (18 to 65 years) with mean baseline BMI of Ͻ35 kg/m 2 , links weight change to blood pressure difference. A systematic review of studies reporting weight differences and blood pressure outcomes, published between 1990 and 2008 with follow-up of Ն2 years identified 8 clinical trials or controlled before and after studies (represented by 9 articles) and 8 cohort studies. Differences ranged from Ϫ11 to ϩ4kg for weight, Ϫ7 to ϩ2.2 mm Hg for diastolic blood pressure and Ϫ13 to ϩ6.1 mm Hg for systolic blood pressure. For this population group, no quantifiable relationship between weight and diastolic blood pressure difference was found, possibly because of small weight losses, differing weight status responses, or because pharmacologically controlled hypertension masked weight loss influences. Systolic differences were in line with previous reviews of 1 kg:1 mm Hg relationship, but only for follow-up periods of 2 to 3 years, possibly reflecting the fact that regardless of maintained weight loss, blood pressure often reverts back to higher levels. Lifestyle interventions for weight and blood pressure are limited in this target group, and there has been no exploration of successful intervention components. An individual patient data analysis may uncover baseline and medication effects, explore differences between weight groups, and may identify successful components. Such an analysis would enable effective development of preventative interventions for both hypertension and obesity. Key Words: lifestyle Ⅲ obesity prevention Ⅲ weight loss Ⅲ blood pressure H ypertension is an important risk factor for cardiovascular morbidity and mortality. 1,2 In adults, hypertension often rises with increasing body weight. 3 Intervention studies and reviews have reported blood pressure reductions associated with weight loss, particularly in the short-term. 4 -6 A recent review of long-term effects of weight loss on hypertension in overweight or obese subjects, excluding surgical weight loss interventions, concluded that blood pressure reduction was about half that found in short-term trials. 7 A leading aim of contemporary public health policy is to reduce levels of obesity, 8 although how to achieve this, or how effective population-level interventions to reduce obesity would be in reducing blood pressure, is still not evident. The aim of this research was to systematically review evidence linking long-term weight and lifestyle changes to blood pressure changes for those with a body mass index (BMI) of Յ35kg/m 2 . MethodsThis review considers longitudinal data rather than "betweentreatment" data linking weight differences with blood pressure differences. Consequently, differences recorded for weight and blood pressure fr...
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