Background Allergic rhinitis is the most common of the allergic diseases. Despite improved understanding of the pathophysiology of allergic rhinitis and advances in its pharmacological treatment, its prevalence has increased worldwide. For patients whose symptoms remain uncontrolled despite medical treatment, allergen injection immunotherapy is advised. An allergen-based treatment may reduce symptoms, the need for medication and modify the natural course of this disease. Objectives To evaluate the e icacy and safety of subcutaneous specific allergen immunotherapy, compared with placebo, for reducing symptoms and medication requirements in seasonal allergic rhinitis patients.

We are just beginning to understand how translational control affects tumour initiation and malignancy. Here we use an epidermis-specific, in vivo ribosome profiling strategy to investigate the translational landscape during the transition from normal homeostasis to malignancy. Using a mouse model of inducible SOX2, which is broadly expressed in oncogenic RAS-associated cancers, we show that despite widespread reductions in translation and protein synthesis, certain oncogenic mRNAs are spared. During tumour initiation, the translational apparatus is redirected towards unconventional upstream initiation sites, enhancing the translational efficiency of oncogenic mRNAs. An in vivo RNA interference screen of translational regulators revealed that depletion of conventional eIF2 complexes has adverse effects on normal but not oncogenic growth. Conversely, the alternative initiation factor eIF2A is essential for cancer progression, during which it mediates initiation at these upstream sites, differentially skewing translation and protein expression. Our findings unveil a role for the translation of 5′ untranslated regions in cancer, and expose new targets for therapeutic intervention.

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Objectives To ascertain hospital inpatient mortality in England and to determine which factors best explain variation in standardised hospital death ratios. Design Weighted linear regression analysis of routinely collected data over four years, with hospital standardised mortality ratios as the dependent variable. Setting England. Subjects Eight million discharges from NHS hospitals when the primary diagnosis was one of the diagnoses accounting for 80% of inpatient deaths. Main outcome measures Hospital standardised mortality ratios and predictors of variations in these ratios.Results The four year crude death rates varied across hospitals from 3.4% to 13.6% (average for England 8.5%), and standardised hospital mortality ratios ranged from 53 to 137 (average for England 100). The percentage of cases that were emergency admissions (60% of total hospital admissions) was the best predictor of this variation in mortality, with the ratio of hospital doctors to beds and general practitioners to head of population the next best predictors. When analyses were restricted to emergency admissions (which covered 93% of all patient deaths analysed) number of doctors per bed was the best predictor. Conclusion Analysis of hospital episode statistics reveals wide variation in standardised hospital mortality ratios in England. The percentage of total admissions classified as emergencies is the most powerful predictor of variation in mortality. The ratios of doctors to head of population served, both in hospital and in general practice, seem to be critical determinants of standardised hospital death rates; the higher these ratios, the lower the death rates in both cases.